bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of norepinephrine on gluconeogenesis in perfused livers of cold-exposed rats
Authors: Shiota M. , Tanaka T. , Sugano T.
Published: December 2017

The effects of norepinephrine and glucagon on gluconeogenesis were studied in hemoglobin-free perfused liver from rats kept for 1-20 days at 4 degrees C. When rats were starved for 24 h at 4 degrees C, the plasma glucose level of rats exposed to cold for 5, 10, and 20 days was significantly higher than that of rats for 1 day, but hepatic glycogen decreased to the same level in all groups. In the isolated perfused liver, basal rates of oxygen consumption and glucose production increased slightly through 5 days of cold exposure and returned to control levels after 20 days of cold exposure. The rates of glucose production from lactate, pyruvate, sorbitol, and glycerol increased by 20-30% after 5 days of cold exposure. The stimulation of gluconeogenesis from these substrates by norepinephrine and phenylephrine increased markedly at all time periods from 1 to 20 days in the cold, with a maximum at 5 days. The stimulation of glycogenolysis by norepinephrine was not affected by cold exposure. The response to catecholamines decreased markedly in liver perfused with calcium-free medium and/or with phentolamine. The stimulation of gluconeogenesis by glucagon increased only in rats exposed to cold for 20 days. The results obtained suggest that the stimulation of hepatic gluconeogenesis by cold is due to an alpha-adrenergic response, and the activation occurs beyond the interaction of norepinephrine with its receptor.
Effect of vasoactive intestinal peptide on isolated perfused rat kidney
Authors: Rosa R. M. , Silva P. , Stoff J. S. , Epstein F. H.
Published: December 2017

Vasoactive intestinal peptide, a polypeptide neurotransmitter, stimulates salt secretion by the mammalian intestine and the rectal gland of the dogfish shark. Because of the recent identification of vasoactive intestinal peptide in renal nerves, the present study was undertaken to investigate its effects on the isolated perfused rat kidney. The addition of vasoactive intestinal peptide to the recirculating perfusate produced a significant increase in urine volume, fractional excretion of sodium, chloride, and potassium, as well as osmolar clearance when compared with control kidneys. These changes associated with addition of vasoactive intestinal peptide occurred without any significant changes in perfusion flow, renal vascular resistance, or inulin clearance. These experiments strongly suggest an action of vasoactive intestinal peptide on renal tubular reabsorption.
Ca2+ transport by mammalian mitochondria and its role in hormone action
Authors: Denton R. M. , McCormack J. G.
Published: December 2017

Three key dehydrogenases in mammalian mitochondria have been found to be activated by Ca2+ with a half-maximal effect at approximately 1 microM. These are pyruvate dehydrogenase, NAD+-isocitrate dehydrogenase, and oxoglutarate dehydrogenase. Activation of these enzymes can also be demonstrated in intact coupled mitochondria when extra mitochondrial Ca2+ is increased in the range of concentrations (0.1 to 2 microM) generally considered to occur in the cytoplasm of normal cells. It is argued that the main role of the calcium transport system in mammalian mitochondria is to relay changes in cytoplasmic Ca2+ into the mitochondrial matrix. Hormones and other extracellular messengers which stimulate ATP-requiring processes such as secretion or muscle contraction through increasing the cytoplasmic concentration of Ca2+ could in this way also increase intramitochondrial oxidative metabolism and hence promote the replenishment of ATP. Recent evidence obtained with heart and liver preparations in support of this view is reviewed.
Sodium retention after adrenal enucleation
Authors: Perrone R. D. , Bengele H. H. , Alexander E. A.
Published: December 2017

Adrenal enucleation (removal of the adrenal gland, leaving the capsule intact) results in regeneration of the adrenal cortex. During the first 1-2 wk of adrenal regeneration, marked renal sodium avidity and positive sodium balance are noted. This renal sodium avidity appears mediated via adrenocorticotropin-stimulated secretion of a potent mineralocorticoid by the regenerating adrenal cortex. In this review, we have examined relationships between the histology and ultrastructure of the regenerating adrenal cortex, renal sodium handling, and adrenal steroid production at various times after the initiation of adrenal regeneration. Plasma levels of known mineralocorticoids are subnormal during the period of most intense sodium avidity, while urinary excretion of a potent mineralocorticoid, 19-nordeoxycorticosterone, has been found to be increased in rats with regenerating adrenals during this period of most intense sodium avidity. This hormone, however, is not elevated in rats with regenerating adrenals after resolution of the period of sodium avidity. In this article, we review the experimental evidence regarding the potency of this mineralocorticoid and its likely role in the sodium retention after adrenal enucleation.
Effects of tolbutamide on gluconeogenesis and glycolysis in isolated perfused rat liver
Authors: Patel T. B.
Published: December 2017

In isolated perfused livers of 24-h fasted rats, perfused with lactate (2 mM), pyruvate (0.5 mM), or dihydroxyacetone (1 mM), infusion of tolbutamide (0.5 mM) very rapidly (within 3 min) inhibited the rate of gluconeogenesis. However, gluconeogenesis from fructose (1 mM) and glycerol (1 mM) was not affected by tolbutamide. Tolbutamide also inhibited by 30% the rate of 14CO2 production from livers perfused with [1-14C]pyruvate, without altering the rate of 14CO2 production from [2-14C]pyruvate. The rate of hepatic glycolysis from fructose, glycerol, and dihydroxyacetone was also stimulated by 250, 40, and 100%, respectively, during tolbutamide infusion into perfused livers. Tolbutamide also inhibited the endogenous rate of hepatic ketogenesis by 30%. All of the tolbutamide-mediated alterations in hepatic metabolism were reversed upon withdrawal of tolbutamide from the perfusion medium. Decreased hepatic gluconeogenesis from lactate and pyruvate in the presence of tolbutamide was not a consequence of increased pyruvate oxidation via the pyruvate dehydrogenase complex or the tricarboxylic acid cycle.
Effect of meal size and frequency on postprandial thermogenesis in dogs
Authors: LeBlanc J. , Diamond P.
Published: December 2017

The influence of meal size and frequency on postprandial thermogenesis was studied in nine mongrel dogs (congruent to 18 kg). Oxygen uptake (VO2) and respiratory quotient (R) were continuously monitored by indirect calorimetry during the following experiments. In expt 1, four dogs were fed on alternated days either a large (3.1 MJ) or small meal (0.77 MJ). In expt 2, five different dogs were fed on alternated days either one large meal (3.1 MJ) or four consecutive small meals (0.77 MJ) spaced at 1.5-h intervals. In expt 3, the four dogs of expt 1 after being sham fed 3 times at 1.5-h intervals were given one large meal (3.1 MJ). The VO2 increase during the initial or cephalic phase (congruent to 50 min) was independent of the meal size but it was directly proportional to the amount of food ingested during the digestive phase. The total thermogenic response to four small meals (125 g) fed at 1.5-h intervals was twice as large as that of one large meal (500 g). One large meal (500 g) preceded by three periods of sham feeding was also found to be more thermogenic than a large meal only. For all experiments the changes in R were seen to parallel the postprandial fluctuations in VO2. These findings indicate that the enhanced heat production obtained when meal frequency is increased is caused by the repeated sensory stimulation produced by palatable food.
Effect of opiate-receptor blockade on normoglycemic and hypoglycemic glucoregulation
Authors: el-Tayeb K. M. , Brubaker P. L. , Lickley H. L. , Cook E. , Vranic M.
Published: December 2017

By use of the opiate antagonist naloxone, we have examined the hormonal and metabolic responses to opiate-receptor blockade under basal conditions and during insulin-induced hypoglycemia in normal dogs. Naloxone treatment had no measurable effect on glucose concentration, turnover, and norepinephrine levels, but stimulated plasma epinephrine, glucagon, and cortisol and inhibited insulin release. Insulin (7 mU X kg-1 X min-1) decreased plasma glucose to 42 +/- 4 mg/dl due to an initial decrease in glucose production and an increase in glucose disappearance. Glucose production then increased, and plasma glucose plateaued. After 50 min of insulin infusion, epinephrine levels increased 26-fold (P less than 0.05), norepinephrine and glucagon 3-fold (P less than 0.02), and cortisol 4-fold (P less than 0.01). Similarly, plasma beta-endorphin and adrenocorticotropin (ACTH) were elevated (6-fold, P less than 0.01, and 16-fold, P less than 0.05, respectively). When naloxone was given during insulin-induced hypoglycemia, there was earlier release of epinephrine, glucagon, beta-endorphin, ACTH, and cortisol as well as a greater release of glucagon (P less than 0.001) and cortisol (P less than 0.0001). This resulted in a greater increase in glucose production (P less than 0.01), thus lessening the insulin-induced hypoglycemic excursion. In conclusion, in the dog, endogenous opiates may play a small role in the regulation of basal insulin and glucagon release and can inhibit the pituitary-adrenal axis under basal conditions and during hypoglycemia. Thus increased glucose production in response to insulin-induced hypoglycemia is consistent with the excessive response of counterregulatory hormones during opiate-receptor blockade.
Generation of plasma free cholesterol from circulating lipoprotein-associated cholesteryl ester
Authors: Goldberg I. J. , Rosenfeld R. S. , Paul I. , Leeman B.
Published: December 2017

Studies were performed to investigate the contribution of lipoprotein-associated cholesteryl ester (CE) in the monkey to circulating free cholesterol (FC). Monkey plasma was incubated with [14C]- or [3H]cholesteryl ester, and radiolabeled low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were isolated by ultracentrifugation. Animals received labeled LDL or HDL. A rapid transfer of CE between lipoproteins was observed, consistent with an active CE transfer protein activity in the monkey. Within 4 h the percent of plasma radioactivity in FC after injection of CE-labeled LDL or HDL was, respectively, 30 and 7% of that of the ester. To determine whether the generation of FC was due to a circulating plasma cholesteryl ester hydrolase, monkey plasma was incubated with CE-labeled lipoproteins with and without 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB). A small amount of FC (less than 3% of the radioactivity) was generated during this incubation but most of the FC production was inhibited by DTNB. Although a small amount of FC can be produced by a plasma cholesteryl esterase (perhaps via reverse action of lecithin-cholesterol acyltransferase), most of the FC in plasma derived from lipoprotein-associated CE is probably due to tissue uptake of lipoproteins and subsequent intracellular hydrolysis of the CE to produce FC.
Urea concentration and ornithine decarboxylase in liver of female rats
Authors: Hitier Y. , Champigny O. , Bourdel G.
Published: December 2017

In virgin female rats thioacetamide administration (1 mg/100 g body wt) induced a 16-fold increase in liver ornithine decarboxylase (ODC) activity and a significant decrease (19%) in hepatic urea concentration. The ornithine-metabolizing enzymes, ornithine-oxo-acid aminotransferase and ornithine carbamoyltransferase, were not modified by the treatment; only carbamoyltransferase, were not modified by the treatment; only carbamoyl-phosphate synthetase I activity was significantly reduced. In 19-day pregnant rats DL-alpha-difluoromethylornithine treatment inhibited the expression of enhanced ODC activity occurring normally at this stage of pregnancy. Concomitantly an inhibition of the usual decrease in hepatic urea was observed. This increase of ureagenesis occurred without any increase in liver N-acetylglutamate or ornithine concentrations, which remained as low as in normal pregnant rats.
Effects of sodium on iodide transport in primary cultures of turtle thyroid cells
Authors: Chow S. Y. , Yen-Chow Y. C. , White H. S. , Woodbury D. M.
Published: December 2017

Iodide uptake by primary cultures of turtle thyroid cells decreased linearly with reduction of Na+ concentration in the medium, but changes in medium Cl- concentration did not affect iodide uptake. Ouabain, furosemide, monensin, and perchlorate all decreased 125I-uptake by cultured thyroid cells, whereas amiloride and triamterene did not. Ouabain, monensin, perchlorate, and amiloride depolarized the membrane of cultured cells, whereas furosemide and triamterene had no effect. Ouabain and perchlorate increased intracellular Na+ and Cl- and decreased K+ activities; furosemide and monensin reduced all three ions, but triamterene had no effect. Amiloride decreased intracellular Na+ and increased intracellular Cl- activities, however, its effect on K+ activity could not be determined because of interference by this compound of the K+ ion exchanger. All the agents, except furosemide, inhibited Na+-K+-ATPase activity. These experiments demonstrate that 1) Na+-I- cotransport is responsible for most iodide accumulation in thyroid cells; 2) Na+-I- cotransport system is linked to the Na+-K+ pump; 3) active iodide transport does not always correlate with Na+-K+-ATPase activity; 4) a perchlorate-sensitive iodide transport system is present in thyroid cells; 5) transport processes, not involved in active iodide transport (Na+-Cl- cotransport and Na+-H+ counter transport), are also present in cultured thyroid cells.
Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection
Authors: Veldhuis J. D. , Johnson M. L.
Published: December 2017

Endocrine signaling provides one critical means of physiological communication within an organism. Many endocrine signals exhibit an episodic or pulsatile configuration. In an effort to provide a versatile and statistically based algorithm for investigating the regulation of endocrine pulse signals, we have formulated a computerized algorithm in which a pulse is defined as a statistically significant increase in a "cluster" of hormone values followed by a statistically significant decrease in a second cluster of values. The increase or decrease is judged in relation to the actual experimental error expressed by the replicates in the presumptive nadir and peak data clusters. The program permits the operator to specify the cluster sizes of test peaks and pre- and postpeak nadirs. This method is largely insensitive to unstable base-line hormone concentrations and is not adversely affected by varying pulse amplitudes, widths, or configurations within the endocrine series. In addition, the simple statistical basis for this algorithm renders it minimally dependent on explicit or a priori assumptions about rates of hormone secretion or disappearance. The program has been validated for false-positive errors against a wide range of intraseries coefficients of variation (4-52%). We have illustrated its performance for profiles of luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, adrenocorticotropic hormone, and cortisol and compared these episodic patterns with those of stable serum constituents (total serum protein and calcium), which do not exhibit pulsatile fluctuation.
H1 action of histamine on aldosterone and cortisol secretion by perfused dog adrenal
Authors: Aikawa T. , Matsumoto I. , Hirose T. , Morikawa T. , Tsujimoto Y.
Published: December 2017

The left adrenal of hypophysectomized-nephrectomized dogs was perfused in situ with artificial medium equilibrated with 95% O2-5% CO2. Repeated secretory responses of aldosterone to ACTH and histamine were almost reproducible during 2 h of perfusion, but those of cortisol and corticosterone gradually reduced. The secretion of aldosterone in response to histamine markedly increased at 1 microM and those of cortisol and corticosterone significantly increased at 1 and 10 microM, respectively. The secretory response of aldosterone to 10 microM histamine was comparable with that to 300 microU/ml ACTH, but the secretory responses of cortisol and corticosterone to 10 microM histamine were very much lower than those to 1 microU/ml ACTH. The secretory responses of these three steroids to 10 microM histamine were almost completely depressed by continuous administration of 10 microM pyrilamine maleate, but not abolished by that of 100 microM metiamide. The secretory responses of these three steroids to 10 microM histamine were slightly depressed by continuous infusion of 10 microM methysergide maleate. These results suggest that histamine at pathophysiological concentrations stimulates the secretion of aldosterone markedly, and those of cortisol and corticosterone slightly, via an H1 receptor of adrenocortical cells in the dog.
Metabolic and circulatory studies of fetal lamb at midgestation
Authors: Bell A. W. , Kennaugh J. M. , Battaglia F. C. , Makowski E. L. , Meschia G.
Published: December 2017

Uterine and umbilical blood flows, the placental clearance of 3H2O, uterine and umbilical uptakes of oxygen, glucose, and lactate were measured in conscious, pregnant sheep at 71-81 days gestation. Fetal weight was 210 +/- 20 g and less than half placental weight. In relation to fetal weight, umbilical flow was 468 +/- 57 ml X min-1 X kg-1, more than double normal values for the mature fetus. Clearance of 3H2O was approximately 12% of the late pregnancy value but high in relation to fetal weight (280 +/- 23 ml X min-1 X kg-1). Fetal oxygen uptake was 10.9 +/- 0.6 ml X min-1 X kg-1, approximately 40% greater than in late gestation. Umbilical uptake of glucose was also relatively high, whereas lactate uptake was low. Uteroplacental tissues consumed more than 80% of the oxygen and glucose taken up by the pregnant uterus. However, uteroplacental utilization rates of oxygen and glucose as well as net lactate production were lower (approximately 50, 30, and 25%, respectively) than in late pregnancy, despite a larger placental mass (486 +/- 22 vs. 302 +/- 12 g).
Renal catabolism of 125I-glicentin
Authors: Lopez-Novoa J. M. , Santos J. C. , Villamediana L. M. , Garrote F. J. , Thim L. , Moody A. J. , Valverde I.
Published: December 2017

The renal catabolism of 125I-glicentin has been studied in vivo by the disappearance of this peptide from the plasma of bilaterally nephrectomized, ureteral-ligated, or normal rats and by using tubular microinfusion techniques. In addition the catabolism of glicentin by the isolated, perfused kidney has been studied. Results from in vivo studies demonstrated that half-disappearance time was lower in control (59.5 +/- 1.8 min) than in bilaterally nephrectomized rats (97.2 +/- 2.6 min), and this value was significantly higher than that of ureteral-ligated animals (83.2 +/- 1.1 min, P less than 0.005). Microinfusion experiments revealed that when 125I-glicentin was injected into the proximal tubule, no trichloroacetic-precipitable radioactivity was recovered in the urine, whereas most of inulin injected was recovered. By contrast most of the 125I-glicentin injected into the distal tubule was recovered in the urine. In isolated kidney experiments, organ clearance rate of 125I-glicentin averaged 0.88 +/- 0.10 ml/min, a value significantly higher than that of glomerular filtration rate (0.72 +/- 0.06 ml/min, P less than 0.005, paired data), and both parameters showed a close linear relationship (r = 0.90). Urinary clearance of glicentin was negligible. These results demonstrate that the kidney plays a major role in the catabolism of glicentin, mainly by glomerular filtration and tubular catabolism. The site of tubular catabolism appears to be the proximal tubule. Peritubular uptake was minimal.
Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver
Authors: Vary T. C. , Siegel J. H. , Nakatani T. , Sato T. , Aoyama H.
Published: December 2017

The effect of chronic sepsis on the concentration of active pyruvate dehydrogenase complex has been investigated in liver and skeletal muscle of normal, sterile inflammatory, and chronic septic (small and large abscess) animals. Hyperdynamic sepsis was induced by the intraperitoneal introduction of a rat fecal-agar pellet of known size and bacterial composition (Escherichia coli + Bacteroides fragilis). Total pyruvate dehydrogenase complex activity was not altered in either liver or skeletal muscle in any of the conditions studied. In hepatic tissue, sterile inflammation increased the proportion of active complex 2.5-fold compared with control. The same increase in the concentration of active complex was observed in animals with a small abscess. When the abscess size was increased (large abscess), the concentration of active complex was decreased relative to sterile inflammatory or small abscess septic animals. In contrast to liver, sterile inflammation did not alter the proportion of active complex in skeletal muscle. Sepsis (either small or large septic abscess) resulted in threefold decrease in the concentration of active complex relative to control or sterile inflammatory animals. Changes in the concentration of active complex did not appear to be dependent on the ATP/ADP concentration ratio or tissue pyruvate levels but were consistent with changes in the acetyl-coenzyme A-to-coenzyme A concentration ratio. The mechanism responsible for altered concentration of active complex may be mediated through changes in the activity of the pyruvate dehydrogenase kinase, secondary to alterations in the effector concentration ratios.
Effects of short-term hyperglycemia on insulin secretion in normal humans
Authors: Ferner R. E. , Ashworth L. , Tronier B. , Alberti K. G.
Published: December 2017

Stepwise glucose clamps were used to study beta-cell insulin response to glucose in normal and noninsulin-dependent diabetic subjects and to study changes in response after hyperglycemia. In normal subjects, insulin increment, delta I, correlated with glucose increment above basal, delta G, during the first 6 min of hyperglycemia, r = 0.748, P less than 0.0001. After 1 h of hyperglycemia, mean delta I/ delta G was reduced from 50 to 23 (mean difference 23 +/- 5) pmol/mmol, P = 0.0002; but delta I/% change in glucose (delta G') was unaltered (2.3 vs. 1.7, mean difference 0.4 +/- 0.3 pmol/%). Second-phase response correlated with mean glucose elevation (r = 0.835, P less than 0.0001), and no plateau was reached after 3 h at 3 mmol/l above basal glucose (rate of change of insulin concentration = 0.5; range, 0.3-0.8 pmol . l-1 . min-1). In diabetic subjects, delta I/ delta G was 20% of normal, while delta I/ delta G' was 63% of normal and second-phase response 30% of normal. We conclude that hyperglycemia per se reduces delta I/ delta G and must be considered when assessing insulin responses. Noninsulin-dependent diabetic subjects have defective first- and second-phase responses.
Heredity and changes in hormones and metabolic rates with short-term training
Authors: Poehlman E. T. , Tremblay A. , Nadeau A. , Dussault J. , Theriault G. , Bouchard C.
Published: December 2017

The purpose of this experiment was to assess the effects of a 22-day training program on resting metabolic rate (RMR), thermic effect of a meal (TEM), and associated hormonal changes. Six pairs of male monozygotic twins were submitted to a 22-day ergocycle exercise program designed to induce a deficit in energy balance of 4.2 MJ per day. RMR and TEM after a 4.2-MJ meal challenge were measured before and after training. Results indicated that RMR and TEM did not change significantly, although a large variation in response between twin pairs was observed. Moreover, training reduced (P less than 0.05) basal and postprandial insulin response, plasma thyroid hormones triiodothyronine (T3), thyroxine (T4), and FT4 (P less than 0.05). Absolute changes in RMR and TEM exhibited significant within-pair resemblance in response, with intraclass correlations reaching r = 0.81 (P less than 0.05) and r = 0.72 (P less than 0.05), respectively. Changes in T4 and FT4 also exhibited moderate within-pair resemblance (0.42 less than or equal to r less than or equal to 0.71). These results suggest that short-term exercise training does not modify RMR and TEM but can significantly decrease plasma levels of insulin and thyroid hormones. Moreover, the similarity of response within twin pairs suggests that heredity plays a role in determining RMR, TEM, and thyroid hormone adaptation to exercise training generating a negative energy balance.
Comparison of thermogenic effect of fructose and glucose in normal humans
Authors: Tappy L. , Randin J. P. , Felber J. P. , Chiolero R. , Simonson D. C. , Jequier E. , DeFronzo R. A.
Published: December 2017

After nutrient ingestion there is an increase in energy expenditure that has been referred to as dietary-induced thermogenesis. In the present study we have employed indirect calorimetry to compare the increment in energy expenditure after the ingestion of 75 g of glucose or fructose in 17 healthy volunteers. During the 4 h after glucose ingestion the plasma insulin concentration increased by 33 +/- 4 microU/ml and this was associated with a significant increase in carbohydrate oxidation and decrement in lipid oxidation. Energy expenditure increased by 0.08 +/- 0.01 kcal/min. When fructose was ingested, the plasma insulin concentration increased by only 8 +/- 2 microU/ml vs. glucose. Nonetheless, the increments in carbohydrate oxidation and decrement in lipid oxidation were significantly greater than with glucose. The increment in energy expenditure was also greater with fructose. When the mean increment in plasma insulin concentration after fructose was reproduced using the insulin clamp technique, the increase in carbohydrate oxidation and decrement in lipid oxidation were markedly reduced compared with the fructose-ingestion study; energy expenditure failed to increase above basal levels. To examine the role of the adrenergic nervous system in fructose-induced thermogenesis, fructose ingestion was also performed during beta-adrenergic blockade with propranolol. The increase in energy expenditure during fructose plus propranolol was lower than with fructose ingestion alone. These results indicate that the stimulation of thermogenesis after carbohydrate ingestion is related to an augmentation of cellular metabolism and is not dependent on an increase in the plasma insulin concentration per se.(ABSTRACT TRUNCATED AT 250 WORDS)
Determination of total adipose tissue and body fat in women by computed tomography, 40K, and tritium
Authors: Sjostrom L. , Kvist H. , Cederblad A. , Tylen U.
Published: December 2017

The adipose tissue volumes of 12 women were determined by computed tomography (CT). Body weight ranged from 46 to 129 kg. Nine or twenty-two transsectional scans were examined with respect to the adipose tissue area. The total adipose tissue volume (ATCT22 or ATCT9) was calculated by assuming linear changes in the adipose tissue area between adjacent scans. Body fat (BF) was also calculated from total body potassium (BF40K), from total body water (BFTHO), and from both these determinations (BF40K + THO). Body mass index (BMI) was calculated by dividing body weight (BW) by height2 (H2). ATCT22, ATCT9, and BFK were more closely related to BW and BMI than were BFTHO and BF40K + THO. When ATCT was used as a standard, the optimal index of adiposity based on BW and H was in the range BW/H0.8 to BW/H1.2. From the CT and 40K measurements it was possible to deduce that the potassium content is 62 mmol/kg fat free mass and 73-75 mmol/kg lean body mass. The error of ATCT9 was 0.6%, while that of BF40K was at least three to four times larger. It is concluded that the CT-based AT determination is the most reproducible method so far available. The technique might turn out to be of great value in human energy balance experiments.
Glutamine and glutamate kinetics in humans
Authors: Darmaun D. , Matthews D. E. , Bier D. M.
Published: December 2017

To study glutamate and glutamine kinetics, 4-h unprimed intravenous infusions of L-[15N]glutamate, L-[2-15N]glutamine, and L-[5-15N]-glutamine were administered to healthy young adult male subjects in the postabsorptive state. Arterialized-venous blood samples were drawn and analyzed for glutamate and glutamine 15N enrichments. The fractional turnover rates of the tracer-miscible glutamate and glutamine pools were fast, 8.0 and 2.8% min-1, respectively. The glutamate tracer-miscible pool accounted for less than one-tenth the estimated free glutamate pool in the body. The plasma glutamate amino N, glutamine amino N and glutamine amide N rates of appearance were 83 +/- 22 (means +/- SD), 348 +/- 33, and 283 +/- 31 mumol X kg-1 X h-1, respectively. The glutamine amide N appearance rate was 20% slower than the amino N appearance rate, indicating that glutamine transaminase is an active pathway in human glutamine metabolism. From measurement of transfer of tracer 15N, we found that only 5% of the glutamine synthesized in cells and released into plasma was derived from intracellular glutamate that had mixed with plasma. These data demonstrate that intravenously administered tracers of glutamate or glutamine do not mix thoroughly with the intracellular pools, and their measured kinetics reflect transport rates through plasma rather than whole-body fluxes.
Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture
Authors: Cronin M. J. , Evans W. S. , Rogol A. D. , Weiss A. A. , Thorner M. O. , Orth D. N. , Nicholson W. E. , Yasumoto T. , Hewlett E. L.
Published: December 2017

Bordetella pertussis synthesizes a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changed the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. We conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is this response that explains the subsequent acceleration of hormone release.
Exercise and diet reduce muscle insulin resistance in obese Zucker rat
Authors: Ivy J. L. , Sherman W. M. , Cutler C. L. , Katz A. L.
Published: December 2017

Two treatments that increase skeletal muscle insulin action are exercise training and high-carbohydrate diet. The purpose of the present study was to determine whether exercise training and a diet high in carbohydrates could function synergistically to reduce the muscle insulin resistance in the obese Zucker rat. Obese rats 4 wk of age were randomly assigned to an exercise or sedentary group. Each group was subdivided by diet with one-half of the rats fed a high-carbohydrate diet and one-half fed a high-fat diet. Lean Zucker rats fed the high-fat diet were used as controls. Muscle insulin resistance was assessed during hindlimb perfusion with a submaximally stimulating concentration of insulin. Exercise training and the high-carbohydrate diet increased the rate of muscle glucose uptake in the obese rat by 46 and 53%, respectively. More importantly, the combined effect of exercise training and high-carbohydrate diet was greater than the sum of their individual effects. Glycogen synthesis paralleled glucose uptake and was the major pathway for intracellular glucose disposal. Muscle glucose uptake for exercise-trained, high-carbohydrate fed obese rats was comparable with that of lean controls. It is concluded that exercise training and the high-carbohydrate diet functioned synergistically to reduce the muscle insulin resistance in the obese rat.
Beta-adrenergic contribution to glucagon-induced glucose production and insulin secretion in uremia
Authors: Baylor P. , Shilo S. , Zonszein J. , Shamoon H.
Published: December 2017

Spontaneous or propranolol-induced hypoglycemia can occur in uremic humans. We studied glucose kinetics (using [3-3H]glucose) in five uremic humans 24 h after hemodialysis and in seven normal controls. The effect of glucagon infusion at rates of 3, 6, 12, and 18 ng X kg-1 X min-1 at 60-min intervals was compared with either saline or beta-adrenergic blockade (propranolol infusion). In uremics, plasma glucose increased by 20-25% and by 40-50% at the 3 and 6 ng X kg-1 X min-1 glucagon doses, respectively, with no further increases at higher infusion rates. Glucose production increased transiently and in tandem with glucose uptake at each glucagon increment (P less than 0.0001). During beta-adrenergic blockade, the effect of glucagon in stimulating glucose production was blunted by 14-24% at the 6-18 ng X kg-1 X min-1 doses (P less than 0.05). During saline infusion, plasma insulin concentrations increased progressively to peak levels fourfold above basal at the 18 ng X kg-1 X min-1 dose. This increase in plasma insulin was virtually abolished by concomitant beta-adrenergic blockade (P = 0.0002). In contrast to uremic subjects, normal controls exhibited lesser degrees of hyperglycemia and hyperinsulinemia at all glucagon infusion rates. Propranolol infusion had no effect on the increments in glucose production and uptake nor on the plasma insulin response. These results suggest that in uremic humans propranolol independently reduces the hepatic response to glucagon and the insulin secretory response to hyperglycemia and/or hyperglucagonemia. These observations provide a possible mechanism for the adrenergic regulation of glucose homeostasis in uremia.
Brown adipose tissue thermogenesis, torpor, and obesity of glutamate-treated mice
Authors: Tokuyama K. , Himms-Hagen J.
Published: December 2017

Mice treated with glutamate in the neonatal period are known to develop into stunted obese adults, despite hypophagia. Our objective was to find out whether brown adipose tissue (BAT) thermogenic function might be abnormal in the glutamate-obese mouse. At 10 wk of age, group-housed glutamate-obese mice exhibited nocturnal and early diurnal torpor, i.e., they thermoregulated at a lower than normal body temperature. When exposed to 4 degrees C, they died in hypothermia within 24 h. They could adapt to living at 14 degrees C for up to 1 wk but failed to adjust their food intake sufficiently to maintain their body weight. Their fat stores were, nevertheless, conserved. BAT was present in increased amounts in glutamate-obese mice. Its thermogenic activity (as assessed by the level of mitochondrial GDP binding) was normal (male mice) or reduced (female mice). A normal thermogenic responsiveness of BAT to cold occurred. The thermogenic response of BAT to a cafeteria diet was normal (male mice) or reduced (female mice). Serum corticosterone concentration was increased in both male and female glutamate-treated mice particularly in the cold. We conclude that the high metabolic efficiency and obesity of the glutamate-obese mouse are principally a consequence of its maintenance of a hypothermic torpid state for more than 50% of the time. An additional deficit in energy expenditure in female, but not male, glutamate-obese mice is associated with suppressed responsiveness of the thermogenic function of BAT to diet and may account for the greater degree of obesity in female than in male glutamate-treated mice.
Potentiating synergism between adenosine diphosphate or triphosphate and acetylcholine on insulin secretion
Authors: Bertrand G. , Chapal J. , Loubatieres-Mariani M. M.
Published: December 2017

The interaction between adenosine di- or triphosphate (ADP or ATP) and acetylcholine (ACh) was studied on insulin secretion. The experiments were performed on the isolated perfused rat pancreas, in the presence of a physiological nonstimulating glucose concentration (5.5 mM). ADP or ATP (1.65 microM) and ACh (0.05 microM) elicited a comparable peak of insulin secretion. When either ATP or ADP was simultaneously infused with ACh, insulin secretory response was significantly higher than the sum of the responses of each agonist applied separately. Similar effects were obtained with stable structural analogues of ATP and ADP (adenylimidodiphosphate, AMP-PNP, and alpha, beta-methyleneadenosine 5'-diphosphate, alpha, beta-methylene ADP) whether they acted alone or in combination with ACh. In contrast, adenosine was ineffective. Furthermore, the study of combined half doses of ATP (or ADP) and ACh allowed us to establish a potentiating synergism between both agonists. These data indicate a potentiating synergism on the beta-cell between ACh and ATP or ADP, the substances acting, respectively, via muscarinic cholinergic receptors and purinergic P2 receptors. So, ATP and ADP by activating P2 receptors could be involved in the parasympathetic control of insulin secretion.
Chronic hypoglycemia increases brain glucose transport
Authors: McCall A. L. , Fixman L. B. , Fleming N. , Tornheim K. , Chick W. , Ruderman N. B.
Published: December 2017

Glucose transport into the brain is depressed in chronically hyperglycemic (diabetic) rats. To determine whether hypoglycemia has the opposite effect, brain transport of hexoses and other substrates was examined in chronically and acutely hypoglycemic rats. We produced chronic hypoglycemia by implanting insulin-secreting tumors or insulin-releasing osmotic mini-pumps or by repeated injection of protamine zinc insulin (PZI) and acute hypoglycemia by intravascular injection of regular insulin. Blood-brain barrier (BBB) transport was measured using the brain uptake index (BUI) method. In the three models of chronic hypoglycemia, brain glucose extraction was increased compared with controls. The extraction of deoxyglucose and several other hexoses was also increased by chronic hypoglycemia. Acute hypoglycemia had no effect on brain transport. The transport of other substrates was either not affected or depressed, suggesting increased brain hexose transport is specific. Studies of freeze-blown brain in insulinoma-engrafted rats showed that brain glucose levels were depressed while creatine phosphate, ATP, and glucose 6-phosphate were maintained. Tumor removal led to a reversion of brain glucose transport to control rates but only after 5-25 days. These findings support the view that glucose transport across the BBB is modulated by chronic alterations in the ambient glucose concentration. They also may explain why some patients with chronic hypoglycemia tolerate low blood glucose concentrations.
Cholesterol metabolism in estrogen-sensitive progestin synthesis by rabbit corpus luteum
Authors: Wittmaack F. M. , Holt J. A. , Schreiber J. R.
Published: December 2017

To learn whether either reduced de novo cholesterol synthesis and/or altered cholesteryl ester metabolism is responsible for the deficient progestin production induced by estrogen withdrawal from pseudopregnant rabbits, we measured the luteal activity of three enzymes: 1) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (the rate-limiting step in de novo cholesterol synthesis), 2) cholesteryl ester hydrolase, and 3) acyl coenzyme A:cholesterol acyltransferase (ACAT) in estrogen-stimulated and estrogen-deprived rabbits. The only change in the activity of these enzymes and of the enzyme NADPH-cytochrome c reductase (a microsomal marker enzyme) after estrogen capsule removal for 12 or 24 h was a 30% decrease in HMG-CoA reductase activity after 24 h. The decrease in HMG-CoA reductase activity was not accompanied by a detectable change in either the content or localization of cellular free cholesterol. Previous data from our laboratory have demonstrated that 24 h of estrogen deprivation has no effect on inner mitochondrial membrane P-450 side-chain cleavage activity (a rate-limiting step in the conversion of cholesterol to steroid hormones). These data, and our earlier finding that estrogen deprivation leads to accumulation of cholesteryl ester in the luteal cells, indicate that estrogen maintains rabbit luteal progestin production by stimulating the transfer of cytoplasmic cholesterol to the active site of P-450 side-chain cleavage on the inner mitochondrial membrane.
Increased insulin sensitivity and responsiveness during lactation in rats
Authors: Burnol A. F. , Leturque A. , Ferre P. , Kande J. , Girard J.
Published: December 2017

In 12-day lactating rats blood glucose and plasma insulin were decreased by, respectively, 20 and 35% when compared with nonlactating rats, despite a 25% increase of their glucose turnover rate. Then, by using the euglycemic hyperinsulinemic clamp technique, dose-response curves for the effects of insulin on glucose production and utilization in lactating and nonlactating rats were performed. Glucose production rate was totally suppressed at 250 microU/ml of insulin in lactating rats and for plasma insulin concentrations higher than 500 microU/ml in nonlactating rats. Plasma insulin level inducing half-maximal inhibition of glucose production was decreased by 60% during lactation. The maximal effect of insulin on glucose utilization rate and glucose metabolic clearance rate was, respectively, increased 1.5- and 2.4-fold during lactation and was obtained for plasma insulin concentrations lower in lactating than in nonlactating rats (250 vs. 500 microU/ml). Insulin concentrations inducing half-maximal stimulation of glucose utilization and glucose metabolic clearance were decreased by 50% during lactation. In conclusion, this study has shown that insulin sensitivity and responsiveness of liver and peripheral tissues are improved at peak lactation in the rat.
Effects of TRH on thyrotroph function and number in rat pituitaries transplanted to renal capsule
Authors: Amr S. , Lippman S. S. , Weintraub B. D.
Published: December 2017

We investigated the function of thyrotrophs in rat pituitaries that were transplanted under the renal capsule of 3-wk-old male Sprague-Dawley rats, which were either intact or hypophysectomized. Groups of 12 animals were implanted with osmotic minipumps that delivered a constant infusion of either thyrotropin-releasing hormone (TRH; 1 mg X kg-1 X day-1) or normal saline for 1 wk. In hypophysectomized rats, TRH infusion led to the appearance of substantial amounts of biologically active serum TSH and prevented the hypothyroidism that occurred in the control group. However, TRH did not change the transplant contents of DNA, immunoactive TSH, and mRNA levels for TSH subunits. Comparison of sellar and renal pituitary tissues, obtained from intact rats after 1 wk of either saline or TRH infusion, showed that removal of the pituitary from hypothalamic influence resulted in a 90% depletion of the thyrotroph TSH content. TRH infusion depleted only 63% of the TSH content of sellar thyrotrophs. The mRNA levels for TSH beta-subunit were similar in sellar and transplanted pituitaries and did not significantly change after TRH infusion. When immunocytochemically stained using rat TSH antiserum, the thyrotrophs in pituitary transplants were morphologically and numerically indistinguishable from the thyrotrophs in sellar pituitaries, in the presence or absence of TRH. These data indicate that in transplanted pituitary, for up to 1 wk of a constant infusion, TRH does not significantly affect either the number of thyrotrophs or their ability to synthesize TSH subunit mRNA. However, it is required to maintain released TSH in circulation, since TSH levels were low in the absence of TRH.(ABSTRACT TRUNCATED AT 250 WORDS)
Glucose-induced changes in pancreatic islet blood flow mediated by central nervous system
Authors: Jansson L. , Hellerstrom C.
Published: December 2017

Earlier experiments with the microsphere technique suggested that a heightened serum glucose concentration consistently leads to an increase in islet blood flow (IBF). Several lines of evidence suggest that this glucose-sensitive control mechanism is located at an extrapancreatic site. The purpose of this study was to define the possible role of the central nervous system in such a mechanism. D-glucose, L-glucose, 3-O-methylglucose, or saline were therefore infused into the carotid artery, each at a dose of 1 mg X kg body wt-1 X min-1 for 3 min, and the pancreatic and islet blood flows were measured. None of these substances affected the systemic serum glucose level. The intracarotid infusion of D-glucose, however, caused a rapid increase in both the serum insulin concentration and IBF. The blood flow to the whole pancreas nevertheless remained unchanged, indicating a redistribution of flow within the gland. Carotid infusion of the other test substances or a similar amount of D-glucose given in a femoral vein did not affect these parameters. Both the increase in serum insulin concentration and the increase in IBF caused by D-glucose could be abolished by vagotomy or administration of atropine. When the systemic blood glucose concentration was increased by intraperitoneal glucose administration (2 g/kg body wt), vagotomy blocked the increase in islet blood flow but not the concomitant insulin release. These observations suggest that the glucose-induced increase in IBF is mediated by vagal cholinergic influences.
Interleukin 1-induced depression of iron and zinc: role of granulocytes and lactoferrin
Authors: Goldblum S. E. , Cohen D. A. , Jay M. , McClain C. J.
Published: December 2017

The mechanism(s) of stress-induced hypoferremia and hypozincemia remains unclear. We studied the role of granulocytes and lactoferrin (LF) in endotoxin and murine interleukin 1 (IL-1)-induced depression of serum Fe and Zn concentrations in both rabbits and rats. Both endotoxin and IL-1 administration induced significant hypoferremia (P less than 0.01) and hypozincemia (P less than 0.01) after 6 h in both species. Granulocyte depletion before IL-1 infusion significantly (P less than 0.01) diminished the hypoferremia but not the hypozincemia. Moreover, infusion of 5 or 15 mg of human LF into rabbits caused significant hypoferremia (P less than 0.005) without hypozincemia. Significant hypozincemia (P less than 0.01) could only be demonstrated after a 75-mg infusion. In contrast, infusions of human transferrin at equivalent doses (5, 15, and 75 mg) induced neither hypoferremia nor hypozincemia. Therefore endotoxin and IL-1-induced hypoferremia and, to a much lesser degree, hypozincemia are granulocyte dependent. Granulocyte released LF is a specific carrier molecule for transport and removal of Fe from the circulation during the acute phase response. The data suggest a mechanistic dissociation of IL-1-induced hypoferremia and hypozincemia with LF-independent mechanisms for Zn.
Effect of exercise intensity and starvation on activation of branched-chain keto acid dehydrogenase by exercise
Authors: Kasperek G. J. , Snider R. D.
Published: December 2017

Branched-chain keto acid (BCKA) dehydrogenase activity was examined in rat skeletal muscle as a function of exercise intensity and nutritional status. The activity of BCKA dehydrogenase increased with increasing exercise intensity, showing increases over resting values of 76, 172, and 245% at 10, 20, and 30 m X min-1. The exercise-induced increase in BCKA dehydrogenase activity was the same in the gastrocnemius and in the quadriceps muscles. Rapid removal of the muscle after death is essential because the activity of BCKA dehydrogenase decreased rapidly after death. Thus the likely reasons Wagenmakers et al. (Biochem. J. 223: 815–821, 1984) found exercise caused a much smaller increase in BCKA dehydrogenase activity than Kasperek et al. [Am. J. Physiol. 248 (Regulatory Integrative Comp. Physiol. 17): R166–R171, 1985] are differences in muscle removal time and the duration of exercise. Starvation for 24 h before exercise increased the exercise-induced activation of BCKA dehydrogenase by 160%, which suggests that the increased BCKA dehydrogenase activity is in response to an increased requirement for citric acid cycle intermediates.