bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin-resistant Na+ pump activity in adipocytes from obese humans
Authors: Mott D. M. , Clark R. L. , Andrews W. J. , Foley J. E.
Published: December 2017

Basal and maximally insulin-stimulated Na+-pump activity was measured in adipocytes from subjects with normal glucose tolerance over a range of body mass indexes (BMI). In a comparison of 13 lean (BMI less than 25) vs. 15 extremely obese (BMI greater than 40) subjects basal activities per unit surface area were similar, but the maximally insulin-stimulated activity was significantly reduced in the extremely obese group [9.2 +/- 0.6 vs. 12.1 +/- 1.0 (min X dam2)-1, P less than 0.05]. The mean percent insulin stimulation of the Na+ pump above basal activity was 48 +/- 7% for the lean compared with 14 +/- 2% for the extremely obese group (P less than 0.001). A similar relationship was observed in these subjects for glucose transport where basal activities per unit surface area again were similar but the maximally insulin-stimulated transport was reduced in the extremely obese subjects (2.2 +/- 0.3 vs 5.1 +/- 0.6 attol/um2 X s, P less than 0.001). These results indicate that alterations in Na+-pump activity may be a manifestation of the insulin-resistant state that could contribute to the development of obesity via decreased cellular thermogenesis.
Altered carnitine metabolism in spontaneously hypertensive rats
Authors: Foster K. A. , O'Rourke B. , Reibel D. K.
Published: December 2017

Carnitine metabolism was examined in spontaneously hypertensive rats (SHR). Carnitine levels were elevated by 25% in hypertrophied hearts of 10- and 15-wk-old SHR when compared with Wistar-Kyoto (WKy) controls. This elevation was associated with a greater than 25% increase in total serum carnitine. The elevated serum carnitine does not appear to be due to increased mobilization from skeletal muscle because carnitine levels were elevated by 25% in gastrocnemius and diaphragm of SHR. Elevated serum carnitine is also not a result of reduced urinary excretion because daily urinary carnitine output was increased by 150% in SHR. These findings suggest that the most likely mechanism for increased serum carnitine is increased carnitine synthesis by the liver. The changes in carnitine metabolism in SHR appear to occur between 5 and 10 wk of age, because the carnitine levels in serum and organs were comparable in 5-wk-old WKy and SHR. The observed alterations in tissue and serum carnitine levels may result in altered fatty acid utilization in SHR.
Regulation of sympathetic activity in lean and obese Zucker (fa/fa) rats
Authors: York D. A. , Marchington D. , Holt S. J. , Allars J.
Published: December 2017

Norepinephrine concentration and turnover (measured by the time-dependent loss of tissue [3H]norepinephrine specific activity) were reduced in the brown adipose tissue (BAT) of obese Zucker rats but were normal in the heart. After acclimation to a 4 degrees C environment for 7 days, BAT norepinephrine turnover was increased to similar levels in lean and obese rats. After overfeeding with sucrose BAT norepinephrine turnover increased in lean rats but was unaffected in obese rats. Propranolol prevented the normalization of BAT mitochondrial GDP binding that followed adrenalectomy of obese rats. Adrenalectomy of obese rats restored BAT norepinephrine turnover to levels observed in lean rats. However, the increase in BAT GDP binding associated with sucrose overfeeding of adrenalectomized lean and obese rats was neither prevented by propranolol nor associated with a stimulation of norepinephrine turnover. The results suggest that the pituitary-adrenal endocrine axis may influence diet-related BAT thermogenesis and that this influence is only partially mediated by the sympathetic nervous system.
Work performance in the iron-deficient rat: improved endurance with exercise training
Authors: Perkkio M. V. , Jansson L. T. , Henderson S. , Refino C. , Brooks G. A. , Dallman P. R.
Published: December 2017

The effect of an endurance training regimen on muscle oxidative enzymes and work performance was studied in iron-deficient and -sufficient rats. Three-week-old male Sprague-Dawley rats (n = 40) were randomly assigned to diets containing either 6 mg iron/kg (iron deficient) or 50 mg iron/kg (iron sufficient). After 2 wk, each group of rats was further divided into untrained or endurance-trained subgroups. Training consisted of daily treadmill running of gradually increasing duration for a 1-mo period. After the training period, sedentary and endurance-trained iron-deficient rats were anemic (Hgb approximately 8 g/dl compared with 16 g/dl in the 2 control groups) and had significantly lower skeletal muscle cytochrome c concentration, cytochrome oxidase activity, and succinic oxidase activity compared with the iron-sufficient groups. In response to training iron-deficient rats also generally had a substantial increase in skeletal muscle oxidative enzymes (P less than 0.05), in contrast to iron-sufficient animals, in which there was little or no training effect. Work performance in response to training in the iron-deficient rats improved more than sixfold in an endurance type of exercise (P less than 0.05), but maximal oxygen consumption during a brief, intense type of exercise was not significantly affected. The results suggest that endurance training of iron-deficient rats results in a milder anemia and less drastic reduction of skeletal muscle oxidative enzymes which in turn allows better performance in an endurance type of exercise.
Identification of tissue insulin receptors: use of a unique in vivo radioreceptor assay
Authors: Whitcomb D. C. , O'Dorisio T. M. , Cataland S. , Shetzline M. A. , Nishikawara M. T.
Published: December 2017

An in vivo radioreceptor assay for polypeptide hormones has been developed and applied to the identification of tissue insulin receptors. The theoretical basis for this assay is presented elsewhere in this issue. 125I-insulin and 131I-albumin were infused into male rats with increasing amounts of unlabeled insulin. Plasma samples were taken at 1-min intervals until the animals were killed at 5 min. Tissue samples were excised and weighed and the activity due to each isotope counted. By comparing the differential distribution of the labeled tracers and applying the results to a compartment model, the specific, displaceable binding of insulin to tissue receptors could be demonstrated. Binding was detected in the liver, muscle, fat, adrenal glands, pancreas, small intestines, and spleen.
Estradiol induces a shift in cultured cells that release prolactin or growth hormone
Authors: Boockfor F. R. , Hoeffler J. P. , Frawley L. S.
Published: December 2017

The process by which estradiol induces an increase in the percentage of prolactin cells in the rat pituitary requires clarification. In this study the effect of estradiol treatment on growth hormone and prolactin cells in monolayer cultures of male rat pituitaries was assessed by use of reverse hemolytic plaque assays. Treatment of cultures with 17 beta-estradiol (10 nM) for 6 days elevated significantly (P less than 0.01) the percentage of all cells in culture that released prolactin without affecting the percentage of growth hormone secretors. However, by sequentially assaying single cells for growth hormone and prolactin, we found that estradiol caused a marked increase (P less than 0.01) in the proportion of individual cells that released both growth hormone and prolactin and a commensurate decrease in the proportion that released growth hormone alone. These results demonstrate that estradiol acts directly on cultures of male pituitary cells to shift the proportions of cells that released growth hormone, prolactin, or both hormones and indicate that estradiol may convert cells that release only growth hormone to those that release both growth hormone and prolactin.
Insulin dose-dependent reductions in plasma amino acids in man
Authors: Fukagawa N. K. , Minaker K. L. , Young V. R. , Rowe J. W.
Published: December 2017

The quantitative relationship between insulin and plasma amino acid (AA) levels were characterized in five healthy young men during euglycemic insulin infusions (6, 10, 30, and 400 mU . m-2 . min-1). The endogenous production and disposal of glucose were determined for the 6 mU . m-2 . min-1 insulin infusion using 6,6-dideuteroglucose. While 8 of 10 AA decreased in a dose-responsive pattern to increasing levels of insulin, alanine and glycine concentrations remained unaffected. For isoleucine and proline, the insulin levels required for a half-maximal response were less than for glucose disposal (P less than 0.05), but, for all other insulin-influenced AA, the levels required were similar to those for glucose disposal. These studies indicate that insulin sensitivity of AA is similar to that of glucose disposal and that AA responses to insulin exhibit a physiologically relevant, dose-response relationship.
Calcitriol corrects bone loss induced by oophorectomy in rats
Authors: Faugere M. C. , Okamoto S. , DeLuca H. F. , Malluche H. H.
Published: December 2017

The effects of calcitriol on histomorphometric parameters of bone structure, formation, and resorption were evaluated in 21 normal or oophorectomized rats. Twelve rats were oophorectomized; six of these received daily subcutaneous injections of 135 pmol of calcitriol for 14 wk starting 38 wk after oophorectomy. Nine rats were sham operated; five of these received the same treatment with calcitriol. There were no differences in serum calcium and phosphorus between sham-operated and oophorectomized animals and rats with or without calcitriol. Calcitriol treatment of sham-operated rats produced an increase in cancellous and cortical bone mass. Oophorectomy resulted in decreased cancellous and cortical bone mass and in a decreased ratio between mineralized and nonmineralized bone. There was no difference in bone-osteoclast interface and osteoid seam width among all groups of rats. Calcitriol corrected, at least in part, the bone loss in oophorectomized animals, normalized the ratio between mineralized and nonmineralized bone, and restored mean growth plate width to normal.
Response of alanine metabolism in humans to manipulation of dietary protein and energy intakes
Authors: Yang R. D. , Matthews D. E. , Bier D. M. , Wen Z. M. , Young V. R.
Published: December 2017

Healthy young adult men were studied with 3 different series of dietary regimens: different levels of protein intake ranging from 1.5 to 0.0 g . kg-1 . day-1; different levels of dietary energy intake; and an excessive intake of protein (3.9 g . kg-1 . day-1). Under each dietary condition, subjects were infused postabsorptively with L-[1-13C]leucine, L-[15N]alanine, and L-[3,3,3-2H3]alanine to measure leucine and alanine kinetics. Leucine flux was significantly reduced when protein intake was restricted (maximum reduction = 24%), but changed insignificantly with dietary energy change or excessive protein intake. Alanine flux and de novo synthesis increased significantly when protein intake was restricted (maximum increase = 50%), changed proportionally with changes in dietary energy, and was significantly reduced with high protein intake. Stepwise regression showed that dietary carbohydrate intake, not protein intake, was the primary factor affecting alanine de novo synthesis. In addition, the alanine 2H tracer produced a 2.5-fold greater measure of alanine de novo synthesis than did the alanine 15N tracer.
Effect of rate of hemorrhage on sympathoadrenal catecholamine release in cats
Authors: Bereiter D. A. , Zaid A. M. , Gann D. S.
Published: December 2017

The effect of rate of blood loss on catecholamine release and cardiovascular compensation to hemorrhage (H) was assessed in alpha-chloralose-urethane anesthetized cats. Arterial blood was withdrawn at a rapid rate (10% measured blood vol/min) or at a slow rate (2%/min), and responses were compared across three volumes of hemorrhage (10, 20, or 30% of total blood vol). Plasma epinephrine did not increase after 10% H, but increased modestly after rapid (199 +/- 25 pg/ml) or slow 20% H (359 +/- 92 pg/ml). In contrast, rapid 30% H evoked a significantly (P less than 0.01) greater increase in epinephrine than slow 30% H (1,827 +/- 274 vs. 630 +/- 165 pg/ml). The rate of hemorrhage had no differential effect on hemorrhage-evoked plasma norepinephrine, but a graded increase was seen with increasing volume of hemorrhage. Similarly, hemorrhage-evoked plasma glucose was proportional to the volume of hemorrhage and was not affected by rate of hemorrhage. Volume of hemorrhage was a good indicator of norepinephrine release after rapid or slow rate of hemorrhage, whereas epinephrine release was well correlated with the mean changes in blood pressure during the posthemorrhage sampling period after rapid or slow rate of hemorrhage. The data indicate that hemorrhage-evoked release of epinephrine depends on the rate of blood loss, but only after large (30%) volumes of hemorrhage. Norepinephrine released into the peripheral circulation demonstrates no dependency on rate of hemorrhage, but is well correlated with volume of hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
Fetal recirculation of amniotic fluid arginine vasopressin
Authors: Ervin M. G. , Ross M. G. , Leake R. D. , Fisher D. A.
Published: December 2017

Amniotic fluid volume reflects a balance between fetal lung fluid and fetal urine production and fluid reabsorption via fetal swallowing. Arginine vasopressin (AVP) infusion decreases both fetal lung fluid and urine production and increases amniotic fluid osmolality and AVP concentration. In the present study we assessed the effect of amniotic fluid AVP injection on plasma AVP (n = 6) and renal function (n = 4) in chronically catheterized fetal lambs (X gestation = 130 days). Thirty minutes after addition of 25 micrograms of synthetic AVP into the amniotic cavity, mean +/- SE fetal plasma AVP increased from a base line of 2.7 +/- 0.2 to 14.6 +/- 3.4 pg/ml (P less than 0.01). One hundred and twenty minutes after injection, plasma AVP had increased to 26.9 +/- 5.7 pg/ml. Fetal urine volume did not change (0.78 +/- 0.01 ml/min) but significant increases in urine osmolality (169 +/- 19 to 315 +/- 25 mosm) and urine sodium (64 +/- 11 to 125 +/- 11 mueq/ml) were observed 120 min after AVP administration. In conclusion, amniotic fluid AVP levels can affect fetal plasma AVP concentration, and AVP absorbed from the amniotic fluid by the fetus remains biologically active.
Triglyceride kinetics: effects of dietary glucose, sucrose, or fructose alone or with hyperinsulinemia
Authors: Kazumi T. , Vranic M. , Steiner G.
Published: December 2017

The effects of different dietary sugars, with or without exogenously induced hyperinsulinemia, on rat plasma triglyceride kinetics have been studied. Glucose, sucrose, or fructose were supplied as 10% drinking solutions. The sugar-supplemented groups were each divided into subgroups, one receiving 6 U of insulin per day for 2 wk from intraperitoneally implanted minipumps and the other receiving none. The same degree of hyperglycemia and of endogenous hyperinsulinemia was seen in each sugar-supplemented group. Infusing exogenous insulin restored normoglycemia and produced more pronounced but equal hyperinsulinemia in each subgroup. In those rats that received no exogenous insulin, triglyceride production increased 18% in the sucrose-supplemented group and 20% in the fructose supplemented subgroups, but not at all in the glucose-supplemented subgroup. This 20% increase in triglyceride production in the fructose-supplemented subgroup was accompanied by a six times greater (120%) increase in triglyceride concentration. This suggested that dietary fructose not only increased triglyceride production, but also impaired triglyceride removal. Exogenously induced hyperinsulinemia further increased triglyceride production in those rats receiving dietary fructose, either as the monosaccharide or as sucrose, but not in those receiving only glucose. Thus, in the presence of fructose, but not glucose, insulin stimulates triglyceride production. As exogenous insulin returned the triglyceride concentrations to normal in the fructose-supplemented rats, it also appeared to overcome any fructose-associated impairment of triglyceride removal.
A method for large volume blood sampling and transfusion in rats
Authors: Berthoud H. R. , Laughton W. B. , Powley T. L.
Published: December 2017

A new protocol that makes it feasible to withdraw large volumes of whole blood from an individual rat within 1 h or less is described. This method involves the use of indwelling catheters for withdrawal of blood from the inferior vena cava with concurrent isovolemic replacement of whole blood into the superior vena cava. Simultaneity of the transfusion and withdrawal, strict equality of volumes, and a smooth exchange of blood are assured by the use of separate channels of the same multiple-channel peristaltic pump for withdrawal and replacement. Validation experiments using both anesthetized and unanesthetized rats indicate that several responses remain essentially undisturbed during large volume blood sampling; these parameters include blood pressure, heart rate, hematocrit, plasma hormones including insulin and glucagon, plasma glucose levels, and feeding behavior. Considerations of technical and physiological limitations of the protocol, including choice of catheters and catheter placement, pump, sampling parameters, and obtaining donor blood, are discussed.
Interpulse interval sequence of LH in normal men essentially constitutes a renewal process
Authors: Butler J. P. , Spratt D. I. , O'Dea L. S. , Crowley W. F.
Published: December 2017

Luteinizing hormone (LH) is released from the anterior pituitary gland in an episodic pattern driven by pulses of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Autocorrelation analysis of the sequence of interpulse intervals of LH secretion in normal men supports the hypothesis that the underlying mechanism driving LH secretion is a renewal process. That is, whatever "memory" the GnRH pulse generator (i.e., the hypothalamus or its antecedent neural drive) may have, it does not go back in time further than the preceding secretory pulse. Thus the hypothalamic timer starts over again each time there is a GnRH secretory episode.
Aggressive behavior in adult male mice elevates serum nerve growth factor levels
Authors: Lakshmanan J.
Published: December 2017

By use of a specific and sensitive beta-nerve growth factor radioimmunoassay (beta NGF-RIA), serum beta NGF concentrations were measured in adult male Swiss-Webster mice under various physiological conditions. Animals killed on the day of arrival from the animal supplier showed wide variations (3-15 ng beta NGF/ml) in serum beta NGF levels. These levels significantly decreased if the animals were maintained under individually housed conditions for at least 6 days prior to death. Aggression caused by social contact between previously individually housed animals raised serum beta NGF levels by two orders of magnitude relative to serum beta NGF concentrations in nonaggressive mice. Testosterone propionate treatment (10 mg/animal) 5 days prior to death did not elevate serum beta NGF levels in individually maintained animals. However, the hormone pretreatment markedly augmented serum beta NGF levels in aggressive mice compared with the levels in hormone-treated nonaggressive animals. Removal of the submandibular-sublingual salivary glands 10 days prior to death completely abolished the increase in serum beta NGF due to aggression. The high serum beta NGF levels, as measured by competitive RIA in aggressive mice, were confirmed by a neurite outgrowth PC-12 bioassay system. In conclusion, serum beta NGF in adult male mice is subject to alteration by environmental stress.
Increased pulmonary uptake of exogenous polyamines after unilateral pneumonectomy
Authors: Rannels D. E. , Addison J. L. , Bennett R. A.
Published: December 2017

Alterations in pulmonary uptake of the naturally occurring polyamine spermidine and of an exogenous polyamine substrate analogue, methylglyoxal bis(guanylhydrazone) (MGBG), were investigated during the early phase of compensatory lung growth after partial pneumonectomy (PNX) in rats. In lungs perfused in situ 3 days after left PNX, when a small (14%) but significant (P less than 0.01) increase in right lung mass could be detected, uptake of [14C]spermidine and of [14C]MGBG from the pulmonary circulation was increased. MGBG uptake exhibited saturation kinetics (1-50 microM MGBG), both in lungs of control animals apparent Km, 11.3 microM; Vmax, 479 pmol X g-1 X min-1) and on the 1st and 3rd post-PNX days. In both PNX groups, the apparent Km of the uptake pathway was decreased somewhat (8.5 microM), while Vmax increased progressively to 584 and 678 pmol X g-1 X min-1 at days 1 and 3, respectively. The effects of PNX on MGBG uptake were detected as early as 3 h after lung resection and were no longer evident when compensatory lung growth was completed 14 days after surgery. In rats adrenalectomized 5 days before left PNX, an accelerated onset and increased rate of lung restoration were associated with a doubling of the effect of PNX alone on MGBG uptake.
Isovolemic hypotension in ovine fetus: plasma arginine vasopressin response and urinary effects
Authors: Ross M. G. , Ervin M. G. , Leake R. D. , Habeeb O. , Fisher D. A.
Published: December 2017

Chronically prepared third trimester fetal lambs were administered intravenous infusions of nitropruside. Mean basal systolic and diastolic blood pressure (59.8 and 42.4 mmHg, respectively) decreased significantly during the infusion (49.2 and 36.8 mmHg, respectively) and increased significantly during the recovery period (66.4 and 48.5 mmHg, respectively). Fetal plasma arginine vasopressin (AVP) significantly increased from a mean basal level of 1.25 +/- 0.09 to 6.81 +/- 0.39 pg/ml during the hypotensive period. Urinary AVP basal levels of 1.21 +/- 0.13 pg/ml increased to 3.18 +/- 0.66 pg/ml during the hypotensive period and 5.87 +/- 0.82 pg/ml during the recovery period (P less than 0.05). The fetal urinary response to nitroprusside appeared biphasic. The hypotensive phase was marked by decreases in both free water and osmolar clearances. During the recovery phase free water clearance remained decreased, while osmolar clearance returned to basal levels. Thus AVP secretion represents an important mechanism for ovine fetal modulation of solute and water excretion in response to utero hypotensive stress.
In vivo metabolic changes as studied longitudinally after ventromedial hypothalamic lesions
Authors: Penicaud L. , Rohner-Jeanrenaud F. , Jeanrenaud B.
Published: December 2017

Ventromedial hypothalamic (VMH)-lesioned rats were tested 1 and 6 wk after the lesions to determine, by euglycemic-hyperinsulinemic clamps, their tissue response to insulin. One week after the lesions, total glucose metabolism was more sensitive and responsive to insulin than in age-matched controls. In the two groups, hepatic glucose production was suppressed at almost identical insulin concentrations (approximately 550 microU/ml). Six weeks after the VMH lesions, the increased insulin responsiveness of total glucose metabolism disappeared and glucose metabolism became less insulin sensitive (right, shifted dose-response curve) than that of control animals. Furthermore, hepatic glucose production of VMH-lesioned rats was now inhibited by 45% at most and at the supraphysiological insulin concentration of 16,000 microU/ml, while it was totally suppressed by 550 microU/ml of the hormone in age-matched controls. This defect was accompanied by a lack of decrease in plasma glucagon levels during the clamps carried out at maximal insulin concentration. In summary, in a first phase after VMH lesion, rats are hypersensitive and hyperresponsive to insulin; and in a later phase, when obesity is well established, VMH-lesioned rats become insulin resistant and are characterized by a decreased in vivo sensitivity and responsiveness of liver and muscles to the hormone.
Leg glucose uptake during maximal dynamic exercise in humans
Authors: Katz A. , Broberg S. , Sahlin K. , Wahren J.
Published: December 2017

Leg glucose uptake (LGU) during submaximal (50% maximal O2 uptake) and maximal dynamic exercise (97%) has been quantified from the product of the leg blood flow and the arterial minus femoral venous glucose concentration. Muscle biopsies were also obtained. During 15 min of submaximal exercise the mean LGU values ranged from 1.07 to 1.25 mmol/min, which demonstrates that LGU was stable under this condition. In contrast, during maximal exercise LGU increased continuously, reaching 2.38 +/- 0.22, 2.95 +/- 0.32, and 3.82 +/- 0.34 mmol/min after 2, 4, and 5.2 min (fatigue), respectively. The mean LGU was negatively related to the mean muscle phosphocreatine content (r = -1.00;P less than 0.01). Intracellular glucose-6-phosphate (G-6-P) and glucose were very low at rest and did not change significantly during submaximal exercise (P greater than 0.05). However, at fatigue G-6-P and glucose increased substantially and were both 8.5 mmol/kg dry muscle (P less than 0.001). These findings demonstrate that during heavy exercise glucose accumulates in the cell probably due to hexokinase inhibition by G-6-P, and thus the rate of glucose utilization appears to be lower than the rate of glucose uptake. It is suggested that 1) LGU during short-term exercise is dependent on the energy state of the muscle and 2) LGU is equal to leg glucose utilization during submaximal exercise but is in excess of utilization during heavy exercise.
Transfer of protein antigens into milk after intravenous injection into lactating mice
Authors: Harmatz P. R. , Hanson D. G. , Walsh M. K. , Kleinman R. E. , Bloch K. J. , Walker W. A.
Published: December 2017

We investigated the transfer of bovine serum 125I-albumin (125I-BSA), bovine 125I-gamma-globulin (125I-BGG), 125I-ovalbumin (125I-OVA), and 125I-beta-lactoglobulin (125I-BLG) from the blood into the milk of lactating mice. Equal amounts (by weight) of the radiolabeled proteins were injected intravenously into mice 1 wk postpartum. Total radioactivity, trichloroacetic acid-precipitable radioactivity, and specifically immunoprecipitable radioactivity were measured in serum, mammary gland homogenate, and milk. Clearance of immunoreactive OVA (iOVA) and iBLG from the circulation was more rapid than iBSA and iBGG. The radioactivity in mammary tissue associated with BSA and BGG was greater than 70% immunoprecipitable throughout the 4-h test interval; 125I-OVA and 125I-BLG were less than 12% precipitable 1 and 4 h after injection. In milk obtained at 4 h, there was an approximately 10-fold greater accumulation of iBSA or iBGG than of iOVA or iBLG. These experiments demonstrate that protein antigens differ in their ability to transfer from maternal circulation into milk. The transfer into milk appeared to be in proportion to persistence of the antigens in the maternal circulation.
Carrier-mediated transport of enkephalins and N-Tyr-MIF-1 across blood-brain barrier
Authors: Banks W. A. , Kastin A. J. , Fischman A. J. , Coy D. H. , Strauss S. L.
Published: December 2017

The saturable, carrier-mediated system capable of the brain-to-blood transport of small peptides with an N-terminal tyrosine was characterized. The rate of disappearance of intraventricularly injected iodinated peptide in the presence or absence of the inhibitor being tested was determined from formulas based on the residual radioactivity in the brains of mice after decapitation. The injection of 100 nmol/mouse of unlabeled N-Tyr-MIF-1 (TMIF) increased the half-time disappearance of 125I-TMIF (ITMIF) in the central nervous system (CNS) from 14.1 to 88.7 min (P less than 0.00005). Technetium, a substance transported out of the brain by the same system that transports iodine, was used as a control; the half-time disappearance of technetium pertechnetate was unaffected by unlabeled TMIF. With two related but distinct techniques, the maximum transport rate out of the CNS (Vmax) for TMIF was 0.266 nmol X g of brain per min (method 1) and 0.297 nmol X g-1 X min-1 (method 2), while the amount of unlabeled material needed to achieve 50% of Vmax (Km) was 15.2 nmol/g (method 1) and 15.1 nmol/g (method 2). The lack of effect of the tyrosinated fragments of TMIF as inhibitors indicates that TMIF is being transported in intact form. The Vmax for methionine enkephalin determined with labeled and unlabeled methionine enkephalin was 0.630 nmol X g-1 X min-1 and the Km was 24.95 nmol/g. Studies with the metabolic modulators furosemide, acetozolamide, reserpine, ouabain, and theophylline suggest that the system is sodium dependent and probably independent of ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)
Continuous versus single bolus enteral nutrition: comparison of energy metabolism in humans
Authors: Nacht C. A. , Schutz Y. , Vernet O. , Christin L. , Jequier E.
Published: December 2017

Continuous respiratory exchange measurements were performed on five women and five men for 1 h before and 6 h after the administration of a milkshake (53% carbohydrates, 30% lipid, and 17% protein energy) given either as a single bolus dose or continuously during 3 h using a nasogastric tube. The energy administered corresponded to 2.3 times the postabsorptive resting energy expenditure. Resting energy expenditure, respiratory quotient, plasma glucose, and insulin concentrations increased sooner and steeper, and plasma free fatty acids levels decreased earlier with the meal ingested as a single dose than with continuous administration. The magnitude of nutrient-induced thermogenesis was greater (P less than 0.01) with the single dose (means +/- SE, 10.0 +/- 0.6%) than with the continuous administration (8.1 +/- 0.5%). The overall (6 h) substrate balances were not significantly different between the two modes of administration. It is concluded that the mode of enteral nutrient administration influences the immediate thermogenic response as well as changes in respiratory quotient, glycemia, and insulinemia; however, the overall nutrient balance was not affected by the mode of enteral nutrient administration.
Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats
Authors: Storlien L. H. , James D. E. , Burleigh K. M. , Chisholm D. J. , Kraegen E. W.
Published: December 2017

High levels of dietary fat may contribute to both insulin resistance and obesity in humans but evidence is limited. The euglycemic clamp technique combined with tracer administration was used to study insulin action in vivo in liver and individual peripheral tissues after fat feeding. Basal and nutrient-stimulated metabolic rate was assessed by open-circuit respirometry. Adult male rats were pair-fed isocaloric diets high in either carbohydrate (69% of calories; HiCHO) or fat (59% of calories; HiFAT) for 24 +/- 1 days. Feeding of the HiFAT diet resulted in a greater than 50% reduction in net whole-body glucose utilization at midphysiological insulin levels (90-100 mU/l) due to both reduced glucose disposal and, to a lesser extent, failure to suppress liver glucose output. Major suppressive effects of the HiFAT diet on glucose uptake were found in oxidative skeletal muscles (29-61%) and in brown adipose tissue (BAT; 78-90%), the latter accounting for over 20% of the whole-body effect. There was no difference in basal metabolic rate but thermogenesis in response to glucose ingestion was higher in the HiCHO group. In contrast to their reduced BAT weight, the HiFAT group accumulated more white adipose tissue, consistent with reduced energy expenditure. HiFAT feeding also resulted in major decreases in basal and insulin-stimulated conversion of glucose to lipid in liver (26-60%) and brown adipose tissue (88-90%) with relatively less effect in white adipose (0-43%). We conclude that high-fat feeding results in insulin resistance due mainly to effects in oxidative skeletal muscle and BAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Hormonal responses associated with early hyperglycemia after graded hemorrhage in dogs
Authors: McLeod M. K. , Carlson D. E. , Gann D. S.
Published: December 2017

Trained, awake, splenectomized dogs (n = 17) were studied to examine potential mechanisms for early hyperglycemia after hemorrhage (H). Animals were surgically prepared under halothane-nitrous oxide 3 days before the experiment. Chronic catheters were placed aseptically in the portal vein (PV), femoral vein, and femoral artery. Electromagnetic flow probes were placed around the PV and hepatic artery. After an overnight fast, dogs were hemorrhaged 10, 20, or 30% of their estimated blood volume in 3 min. Flow measurements and blood samples for glucose (G), immunoreactive insulin (IRI), immunoreactive glucagon (IRG), catecholamines (C), and cortisol (F) were taken prior to H and from 5 min to 8 h post-H. Plasma IRI, IRG, and F were measured by radioimmunoassay, plasma C by high-pressure liquid chromatography, and G by a glucose oxidase method. Peripheral G did not change after 10% H but increased significantly after 20 and 30% H from 10 min to 2 h. Similarly, peripheral C did not change after 10% H but increased significantly from 10 min to 2 h after 20 and 30% H. In contrast, the portal venous delivery of IRG did not increase significantly until at least 1 h after any magnitude of H. Peripheral IRI did not change after any magnitude of H. However, portal venous delivery of IRI decreased significantly from 20 min to 6 h after 10% H. Plasma F increased significantly in peripheral blood after all magnitudes of H. These results indicate that an increase in the release of IRG occurs too late to account for the early hyperglycemia that occurs during the 1st h following H.(ABSTRACT TRUNCATED AT 250 WORDS)
alpha-Ketoisocaproate is superior to leucine in sparing glucose utilization in humans
Authors: Buckspan R. , Hoxworth B. , Cersosimo E. , Devlin J. , Horton E. , Abumrad N.
Published: December 2017

The present study was designed to examine the glucose-sparing effect of leucine and its keto acid alpha-ketoisocaproate (KIC) in vivo. Two groups of overnight-fasted normal volunteers were studied. In the first group, eight subjects received an intravenous infusion of leucine and six subjects received KIC (2.3 mumol X kg-1 X min-1) for 3 h; on another occasion, all subjects received saline and acted as their own controls. In the second group, 11 subjects received an infusion of 1 mU X kg-1 X min-1 for 3 h with a variable glucose infusion to maintain euglycemia. On another occasion, five subjects received an additional infusion of leucine and six subjects received KIC each at 2.3 mumol X kg-1 X min-1 for 3 h. The amount of exogenous glucose required to maintain euglycemia (M, mg X kg-1 X min-1) was used as an index of total body glucose utilization. Forearm exchange of leucine, KIC, glucose, and lactate was determined in both groups. Both leucine and KIC infusions alone decreased glucose uptake (42 and 40%) and increased lactate release (37 and 116%, respectively). Hyperinsulinemia (6-fold basal) and euglycemia resulted in a fivefold increase in glucose uptake across the human forearm. The amount of exogenous glucose required to maintain euglycemia averaged 7.4 +/- 0.5 mg X kg-1 X min-1. The combination of leucine and insulin infusions did not alter the stimulated forearm glucose uptake nor did it change M (7.25 +/- 0.6 mg X kg-1 X min-1, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin-sensitive glucoreceptors in rat preoptic area that regulate FFA mobilization
Authors: Coimbra C. C. , Migliorini R. H.
Published: December 2017

Previous studies indicated that a longitudinal pathway connecting preoptic, lateral, and posterior hypothalamic areas participates in the process of free fatty acid (FFA) mobilization in the rat. In the present experiments, the presence of sensitive neurons in the preoptic area was investigated by examining the effects of topical stimulation with 2-deoxyglucose (2-DG) or insulin on the levels of plasma FFA in conscious unrestrained rats. Microinjections of minute amounts (50 micrograms and 1 microliter) of 2-DG into the preoptic area of fed animals induced rapid increases in the concentration of plasma FFA. Microinjections of insulin (5 microU and 0.5 microliter) produced sharp decreases of the elevated plasma FFA levels in fasted rats. Both 2-DG and insulin induced small increases in plasma glucose that did not differ from similar increases induced by equal volumes of 0.15 M NaCl. The results provide direct evidence for the presence within the preoptic area of insulin-sensitive glucoreceptors involved in FFA mobilization. The data suggest that activation of these receptors and increased sympathetic outflow to adipose tissue contributes to fasting lipolysis.
Acute effect of calcium and insulin on hyperfiltration of early diabetes
Authors: Bank N. , Lahorra M. A. , Aynedjian H. S.
Published: December 2017

We examined the effect of calcium administration on renal hyperfiltration in streptozotocin-treated diabetic rats. Rats were studied 7–10 days after streptozotocin injection. Intrarenal infusion of CaSO4 in Ringer's solution had no effect on the hyperfiltration of the diabetic kidney. Infusion of insulin in a dose that did not effect hyperglycemia also had no effect on the hyperfiltration. However, when insulin and calcium were infused together, a rapid decrease in glomerular filtration rate, single-nephron filtration rate, glomerular hydraulic pressure, and renal plasma flow occurred. The contralateral control kidney was unaffected. Verapamil infusion had no significant effect in untreated diabetic rats, but immediately reversed the vasoconstriction induced by insulin plus calcium. Similar intrarenal insulin and calcium infusions had no effect in euvolemic or chronically salt-loaded nondiabetic rats. The observations indicate that renal vascular cells (probably preglomerular) are hyperresponsive to calcium in early insulin-dependent diabetes mellitus and that this response requires insulin. We suggest that decreased renal vascular tone in early insulin-dependent diabetes mellitus may be due in part to defective transmembrane calcium flux across vascular smooth muscle cells. Insulin appears to be required for calcium entry or mobilization, to initiate renal vascular smooth muscle contraction in diabetes.
Influence of zinc on growth, somatomedin, and glycosaminoglycan metabolism in rats
Authors: Bolze M. S. , Reeves R. D. , Lindbeck F. E. , Elders M. J.
Published: December 2017

Weanling male rats were fed control ad libitum, zinc-deficient (ZD, 1 ppm zinc) or pair-fed (PF) control diets for 13 days. Rats subsequently were refed control diets for up to 8 days and serially killed. ZD and PF diets significantly decreased growth rate, feed intake, and feed efficiency compared to controls. Body weight and feed efficiency, but not feed intake, were significantly less in ZD compared to PF. Bone zinc was 315, 286, and 109 micrograms/g (p less than 0.0001) for control, PF, and ZD at the end of depletion. 35SO4 uptake by glycosaminoglycans (GAG) was significantly less in ZD compared to either control ad libitum or PF rats. Xylosyltransferase activity was decreased significantly below PF and control by ZD, suggesting depressed enzyme activity and/or decreased GAG acceptor sites. Bioassayable somatomedin (Sm) activity was 0.81, 0.42 and 0.33 +/- 0.09 relative activity for control, PF and ZD at the end of depletion. Sm was statistically less in ZD compared to PF at day 2 and 5 of refeeding, but not at the end of depletion. Sm activity and GAG metabolism returned to normal after refeeding for 2–5 days in PF and for 5-8 days in ZD rats. Serum insulin but not glucose was significantly depressed by ZD and PF diets. Thus, zinc deficiency depressed growth and cartilage metabolism and was associated with decreased Sm activity and insulin levels. Some of these changes could be attributed to decreased feed intake as a result of ZD.
Cold-induced increase in brown fat thyroxine 5'-monodeiodinase is attenuated in Zucker obese rat
Authors: Wu S. Y. , Stern J. S. , Fisher D. A. , Glick Z.
Published: December 2017

In this study we examined the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for enzymic conversion of thyroxine (T4) to triiodothyronine (T3) in BAT. A total of 34 lean and obese rats, approximately 4 mo old were divided into three treatment groups: group 1 (5 lean and 6 obese) was fed Purina rat chow for 21 days, and group 2 (5 lean and 6 obese) was fed a cafeteria diet for 21 days, and group 3 (6 lean and 6 obese) was fed Purina rat chow and maintained in the cold (8 +/- 1 degrees C) for 7 days. The lean and obese rats in all three groups of animals were matched closely for age and respective body weight. Activity of T4 5'-deiodinase was determined as the rate of T3 production from added T4 under controlled in vitro conditions. Serum T4 and T3 were determined by radioimmunoassay. The rate of T4-to-T3 conversion in BAT was similar in the lean and obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet (approximately 40-50 pmol T3/scapular BAT depot per h). However, expressed per scapular BAT depot, lean rats exposed to cold displayed about a fivefold increase in BAT T3 production (P less than 0.0001), whereas only a small increase was observed in the cold-exposed obese rats. Serum T3 levels tended to be reduced in the Zucker obese rats. Our data indicate a reduced capacity for T3 production in Zucker rat BAT exposed to cold.(ABSTRACT TRUNCATED AT 250 WORDS)
Triiodothyronine stimulates cartilage growth and maturation by different mechanisms
Authors: Burch W. M. , Van Wyk J. J.
Published: December 2017

The mechanisms by which triiodothyronine (T3) stimulates growth and maturation of growth-plate cartilage in vitro were studied by incubating embryonic chick pelvic cartilages in serum-free medium in the presence and absence of T3 for 3 days. To determine whether T3 might stimulate production of somatomedins by the cartilage, medium from cartilage incubated with and without T3 was assayed for somatomedin C (Sm-C) by radioimmunoassay. No difference in Sm-C content was found. However, cartilage incubated with T3 and increasing amounts of human Sm-C (0.5-20 ng/ml) weighed more and had greater amounts of glycosaminoglycan than cartilage incubated in the same concentrations of Sm-C without T3, suggesting that T3 enhances the growth effect of somatomedin. We added a monoclonal antibody to Sm-C (anti-Sm-C) to the organ culture to determine whether T3's stimulatory effect on cartilage growth could be blocked. The anti-Sm-C inhibited growth of cartilage incubated in medium alone and blocked the growth response to T3. By using alkaline phosphatase as a biochemical marker to follow maturation, we found that T3 stimulated a 57% increase in alkaline phosphatase activity above cartilage incubated in medium alone and that anti-Sm-C did not inhibit T3's stimulatory effect on alkaline phosphatase activity. We propose two different mechanisms by which T3 affects growth-plate cartilage: T3 promotes cartilage growth primarily through enhancing the effect of somatomedin, and T3 stimulates cartilage maturation possibly by accelerating the normal process of cartilage differentiation from proliferative to hypertrophic chondrocytes.
Lipolytic response to glucose infusion in human subjects
Authors: Wolfe R. R. , Peters E. J.
Published: December 2017

We have determined the effect of various rates of glucose infusion on the rates of release of glycerol (Ra glycerol), free fatty acids (Ra FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and [1-13C]palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on Ra glycerol and Ra FFA was dose-dependent. At an infusion rate of 1 mg X kg-1 X min-1, no effect on either kinetic factor was noted. At 4 mg X kg-1 X min-1, both Ra glycerol and Ra FFA were suppressed; at 8 mg X kg-1 X min-1, Ra FFA was even more depressed, but Ra glycerol was similar to the value during the 4 mg X kg-1 X min-1 infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue.
Effect of warm or cold exposure on GDP binding and uncoupling protein in rat brown fat
Authors: Trayhurn P. , Ashwell M. , Jennings G. , Richard D. , Stirling D. M.
Published: December 2017

The effects of acute and chronic exposure to different environmental temperatures on the total tissue cytochrome oxidase activity, level of mitochondrial GDP binding, and specific mitochondrial concentration of uncoupling protein have been investigated in rat brown adipose tissue, a radioimmunoassay being used to measure uncoupling protein. Acclimation at different temperatures for 3 wk produced parallel changes in GDP binding, the concentration of uncoupling protein, and the activity of cytochrome oxidase, each parameter rising with decreasing temperature between thermoneutrality (29 degrees C) and 4 degrees C. Acute exposure of warm-acclimated (29 degrees C) rats to the cold (4 degrees C) led to a rapid increase in GDP binding without any alteration in the amount of uncoupling protein. The increase in binding was accompanied by an increase in the rate of acetate-induced swelling of the mitochondria. The concentration of uncoupling protein in warm-acclimated rats was significantly raised only after 48 h exposure to cold. When cold-acclimated rats were exposed acutely to the warm, there was a rapid decrease in GDP binding without any alteration in the amount of uncoupling protein. It is concluded that after alterations in environmental temperature the concentration of uncoupling protein in brown adipose tissue mitochondria changes much more slowly than GDP binding and that binding can therefore be dissociated from the amount of the protein.
Transport epithelial characteristics of cultured bovine pituitary follicular cells
Authors: Ferrara N. , Fujii D. K. , Goldsmith P. C. , Widdicombe J. H. , Weiner R. I.
Published: December 2017

Confluent monolayers of polygonal epithelioid cells were obtained from enzymatically and mechanically dispersed bovine anterior pituitaries (AP) and pars tuberali (PT). The ultrastructure of the cells composing the monolayer was consistent with the follicular or folliculostellate cells (FC) of the pituitary, i.e., lack of secretory granules; formation of follicles in culture; interdigitations with neighboring cells with numerous tight junctions; presence of extensive microfilaments; and sparse rough endoplasmic reticulum and Golgi apparatus. Culture media from monolayers of first passage cultures contained little if any of the AP hormones' luteinizing hormone, prolactin, and ACTH. Shortly after reaching confluency, regions of the monolayer bulge away from the surface of the culture dish to form domes. Dome formation has been described only with cultures of cells that function as transport epithelia in vivo. FC cultured on polycarbonate filters were placed in Ussing chambers. A transepithelial potential difference of approximately 1.1 mV and a resistance greater than 300 omega cm2 were detectable 4–5 days after plating. The short-circuit current (Isc) was decreased 70% by amiloride applied to the mucosal surface and further decreased by the addition of ouabain at the serosal surface. The beta-adrenergic agonist isoproterenol increased the Isc and this action was prevented by a beta-antagonist. These observations indicate that pituitary FC in culture behave as a transport epithelium. Considering the organization of FC in the AP and PT, they suggest a regulatory role for FC in the maintenance of the ionic composition of the interstitial fluid of the pituitary gland.