bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects
Authors: Wolfe R. R. , Peters E. J. , Klein S. , Holland O. B. , Rosenblatt J. , Gary H.
Published: December 2017

In this study the rate of lipolysis (fatty acid and glycerol release into blood) has been quantified in both normal weight and obese volunteers after both 15 and 87 h of fasting. In each study, the basal rate and subsequent response to epinephrine infusion (0.015 microgram X kg-1 X min-1) were determined. The rate of appearance (Ra) of free fatty acids (FFA) and glycerol were quantified by infusion of [1-13C]palmitate and D-5-glycerol, respectively. Substrate flux rates per unit of body fat mass and lean body mass were calculated from total body water measurements using H2(18)O dilution. In normal volunteers, the basal Ra FFA and Ra glycerol rose markedly with 87 h of fasting, whereas the increases were more modest in the obese subjects. However, the rate of mobilization of fat, in relation to the lean body mass, was higher in the obese subjects than in the normal subjects after 15 h of fasting, and the values were similar in both groups after 87 h of fasting. There was an increased lipolytic response to epinephrine after fasting in both groups. This increased sensitivity may have resulted from the enhancement of fatty acid-triglyceride substrate cycling that occurred after fasting.
Increased sensitivity of the genetically obese mouse to corticosterone
Authors: Tokuyama K. , Himms-Hagen J.
Published: December 2017

Adrenalectomy normalizes many abnormalities of the obese (ob/ob) mouse. The high corticosterone concentration in blood may account in part for development of obesity and other abnormalities in the ob/ob mouse. Our objective was to determine dose-response relationships for the effect of corticosterone on the obesity. Lean and ob/ob mice were adrenalectomized or sham-operated at 4.5 wk of age. Adrenalectomized mice received 100 mg implants of cholesterol containing corticosterone (0, 2, 5, 20, or 50 mg) at 8.5 wk of age and were killed at 10.5 wk of age. In ob/ob mice, but not in lean mice, low physiological levels of serum corticosterone (up to 10 micrograms/dl) markedly increased body weight gain, food intake, and serum insulin. They also increased white and brown adipose tissue weights and decreased brown adipose tissue mitochondrial GDP binding. Higher levels of corticosterone (12-22 micrograms/dl) increased body weight gain, white and brown adipose tissue weights, and serum insulin and suppressed brown adipose tissue mitochondrial GDP binding in lean mice also, although in most cases to a lesser extent than in ob/ob mice, but were still without effect on food intake. Only very high levels of corticosterone (approximately 30 micrograms/dl) increased food intake in lean mice. Hyperglycemia was induced in ob/ob, but not lean, mice only at concentrations of corticosterone greater than 17 micrograms/dl. Thermoregulation was unaffected by serum corticosterone at levels from 0 to 30 micrograms/dl in both ob/ob and lean mice. Thus the ob/ob mouse is excessively sensitive and responsive to an effect of physiological levels of corticosterone that results in hyperphagia, hyperinsulinemia, and increased weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)
Beta-endorphin-induced hyperglycemia in rabbits: effects of a glucose or arginine challenge
Authors: Schleicher R. L. , Chawla R. K. , Coan P. A. , Martino-Saltzman D. , Collins D. C.
Published: December 2017

The effects of beta-endorphin on glucose, insulin, and glucagon levels were studied in normal fasted adult male rabbits. An intravenous bolus of glucose (0.7 g/kg body wt) produced a hyperglycemic state (peak plasma glucose 306 +/- 22 mg/dl; means +/- SE) that lasted approximately 90 min. beta-Endorphin (31 micrograms/g body wt; iv) administered immediately prior to the glucose challenge resulted in plasma glucose levels that were significantly higher from 10 to 90 min after the glucose challenge (P less than 0.001-0.05). From 10 to 30 min, plasma insulin levels were significantly lower in the beta-endorphin group (P less than 0.001-0.05), peaking at one-half the control group levels. Glucagon levels were unchanged by the glucose bolus in either the control or beta-endorphin-treated group (means +/- SE = 102.8 +/- 4 pg/ml). In another experiment, a 30-min infusion of L-arginine (13 mg-1 X kg body wt-1 X min iv) in normal fasted rabbits produced a rapid (10 min) increase in plasma insulin and glucagon and a return to base-line levels 60 min after withdrawing the arginine stimulus. Plasma glucose levels were not altered by arginine (mean +/- SE = 94.5 +/- 1 mg/dl). Administration of beta-endorphin (31 micrograms/kg body wt iv) at the start of the arginine infusion resulted in a rapid (10 min) and long-lasting (up to 60 min) hyperglycemic effect associated with a significant decrease in insulin levels (10-20 min; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Thyroid function and cold acclimation in the hamster, Mesocricetus auratus
Authors: Tomasi T. E. , Horwitz B. A.
Published: December 2017

Basal metabolic rate (BMR), thyroxine utilization rate (T4U), and triiodothyronine utilization rate (T3U) were measured in cold-acclimated (CA) and room temperature-acclimated (RA) male golden hamsters, Mesocricetus auratus. Hormone utilization rates were calculated via the plasma disappearance technique using 125I-labeled hormones and measuring serum hormone levels via radioimmunoassay. BMR showed a significant 28% increase with cold acclimation from 4.50 +/- 0.05 to 5.77 +/- 0.10 ml O2 X h-1 X g-2/3. The same cold exposure also produced a 32% increase in T4U (10.75 +/- 0.51 vs. 14.19 +/- 0.75 ng X day-1 X g-2/3), and a 204% increase in T3U (5.51 +/- 0.53 vs. 16.77 +/- 1.35). The much greater increase in T3U implies that previous assessments of the relationship between cold acclimation and thyroid function may have been underestimated and that cold exposure induces both quantitative and qualitative changes in thyroid function. It is concluded that in the cold-acclimated state, T3U more accurately reflects thyroid function than does T4U. A mechanism for the cold-induced change in BMR is proposed, for which alterations in four aspects of thyroid function are required: a decrease in plasma T4 binding, an elevation of the pituitary T4 "set point," a preferential shift in deiodinase activity from reverse T3 to T3 production, and an increase in the thyroidal secretion of T3.
Regulation of albumin synthesis by hormones and amino acids in primary cultures of rat hepatocytes
Authors: Hutson S. M. , Stinson-Fisher C. , Shiman R. , Jefferson L. S.
Published: December 2017

Culture conditions necessary for optimizing albumin secretion were studied in rat hepatocytes maintained in a chemically defined, serum-free medium. Amino acid analysis of the culture medium, which was based on a 1:1 mixture of Ham's F12:Dulbecco's modified Eagle's medium (unsupplemented medium), revealed that certain essential amino acids were depleted from this medium over a 24-h incubation. Rates of albumin secretion were significantly higher and better maintained when the medium was supplemented with additional amino acids (supplemented medium). Moreover, selective removal of an essential amino acid resulted in an immediate decrease in total protein and albumin synthesis and after 48 h a further selective decrease in albumin synthesis. Linear rates of albumin secretion were observed over a wide variety of experimental conditions, but secretion was not strictly proportional to cell number. Maximal rates of secretion were obtained at plating densities of 2–3 X 10(6) cells/60 mm culture dish. Albumin secretion also increased with time in culture reaching a maximum on days 3 and 4. When added singly, either insulin or dexamethasone increased rates of albumin secretion in a dose-dependent manner, but both hormones and an adequate supply of amino acids were necessary for maximal rates of secretion as well as long-term maintenance of the hepatocytes (greater than 3–4 days). In the presence of dexamethasone the dose-response curve for insulin was shifted toward physiological insulin concentrations. Changes in rates of albumin secretion in response to added hormones in supplemented media were found to parallel changes in albumin synthesis and relative amounts of albumin mRNA. Changes in gene transcription were probably involved.
Epinephrine potentiates adenosine-stimulating effect on glucagon secretion
Authors: Gross R. , Bertrand G. , Ribes G. , Petit P. , Loubatieres-Mariani M. M.
Published: December 2017

The aim of the present work is to investigate a possible interaction on glucagon secretion between adenosine, a compound released by tissues in energy-deficient states, and epinephrine, the hormone of stress largely implicated in such conditions. The study was performed using the isolated perfused rat pancreas in presence of a physiological glucose concentration (5 mM). Epinephrine administered at a low concentration (0.01 microM) was ineffective on glucagon secretion, and adenosine at 1.65 microM was previously shown to be moderately stimulating. This nucleoside alone induced a transient increase of glucagon secretion rate that peaked at 300% of basal value at 2 min; in presence of epinephrine (ineffective per se) the rise induced by the nucleoside alone was doubled. This potentiating effect was not observed with the neurotransmitter norepinephrine at the dose tested. Propranolol (1 microM) did not alter the potentiating effect of epinephrine but this effect was completely suppressed by the alpha-blocker, phenoxybenzamine (6 microM). In conclusion epinephrine potentiates an adenosine-stimulating effect on glucagon secretion; this effect seems more specific for the adrenal medulla hormone epinephrine, since norepinephrine at the same dose is ineffective; it is mediated via alpha-adrenergic receptors. It is attractive to speculate that epinephrine and adenosine act in potentiating synergism on glucagon secretion; this might be of physiological importance during stressful energy-deficient situations.
Diet-induced thermogenesis in cafeteria-fed rats: a myth?
Authors: Maxwell G. M. , Nobbs S. , Bates D. J.
Published: December 2017

Oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient were measured in rats given a high-fat cafeteria diet of the type that is said to promote diet-induced thermogenesis. No significant difference in the measurements as compared with controls was found at room temperature, at 5 degrees C, or in animals exposed to cold for several weeks. The result was the same whether open- or closed-circuit methods were used. The stimulatory effect of norepinephrine on the VO2 was identical in each dietary group. These results cast doubt on the alleged identity of diet-induced and nonshivering thermogenesis and may reflect the change in body composition of the animals rather than a primary response to dietary variation.
Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting
Authors: Hendrick G. K. , Frizzell R. T. , Cherrington A. D.
Published: December 2017

In the 7-day fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (Rd) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in Rd. In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon ("hormone replacement"), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion ("hormone replacement + NEFA"). Glucose turnover was assessed using [3-3H]glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. Rd was constant during saline infusion, increased in the hormone replacement protocol, but was constant in the hormone replacement plus NEFA protocol. After a prolonged fast in the dog, 1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and 2) this decrease in the NEFA level causes an increase in Rd.
Increased glucose dependence in resting, iron-deficient rats
Authors: Brooks G. A. , Henderson S. A. , Dallman P. R.
Published: December 2017

Rates of blood glucose and lactate turnover were assessed in resting iron-deficient and iron-sufficient (control) rats to test the hypothesis that dependence on glucose metabolism is increased in iron deficiency. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient group) for 3-4 wk. The iron-deficient group became anemic, with hemoglobin levels of 6.4 +/- 0.2 compared with 13.8 +/- 0.3 g/dl for controls. Rats received a 90-min primed continuous infusion of D-[6-3H]glucose and sodium L-[U-14C]lactate via a jugular catheter. Serial samples were taken from a carotid catheter for concentration and specific activity determinations. Iron-deficient rats had significantly (P less than 0.05) higher blood glucose (7.1 +/- 0.3 vs. 6.1 +/- 0.2 mM) and lactate concentrations than controls (1.0 +/- 0.1 vs. 0.8 +/- 0.1 mM). The iron-deficient group had a significantly higher glucose turnover rate (67 +/- 2 vs. 58 +/- 4 mumol . kg-1 . min-1) than the control group. Significantly more metabolite recycling in iron-deficient rats was indicated by greater incorporation of 14C (from infused [14C]-lactate) into blood glucose. Assuming a carbon crossover correction factor of 2, half of blood glucose arose from lactate in deficient animals. By comparison, only 25% of glucose arose from lactate in controls. Lack of a difference in lactate turnover (irreversible disposal) rates between deficient rats and controls (191 +/- 26 vs. 163 +/- 15 mumol . kg-1 . min-1) was attributed to 14C recycling.(ABSTRACT TRUNCATED AT 250 WORDS)
Modified protocols improve insulin sensitivity estimation using the minimal model
Authors: Yang Y. J. , Youn J. H. , Bergman R. N.
Published: December 2017

We attempted to improve the precision of the estimation of insulin sensitivity (S1) from the minimal model technique by modifying insulin dynamics during a frequently sampled intravenous glucose tolerance test (FSIGT). Tolbutamide and somatostatin (SRIF) were used to change the insulin dynamics without directly affecting insulin sensitivity. Injection of tolbutamide (100 mg) at t = 20 min provoked an immediate secondary peak in insulin response, resulting in a greater integrated incremental insulin than the standard FSIGT. SRIF, injected at t = -1 min, delayed insulin secretion in proportion to the dose without any change in magnitude. Computer simulation was used to assess the precision of S1 estimation. Insulin dynamics from both standard and modified protocols were adjusted in magnitude, with the shape unchanged and analyzed to determine the effect of the magnitude of insulin response. Fractional standard deviation was reduced from 73% with the standard insulin profile to 23% with tolbutamide and 18% with the highest dose of SRIF. In addition, the fractional standard deviation of S1 estimates decreased exponentially with increasing magnitude of insulin response. Modified FSIGTs require a smaller insulin response than the standard protocol to achieve the same precision.
Infusion and sampling site effects on two-pool model estimates of leucine metabolism
Authors: Helland S. J. , Grisdale-Helland B. , Nissen S.
Published: December 2017

To assess the effect of site of isotope infusion on estimates of leucine metabolism infusions of alpha-[4,5-3H]ketoisocaproate (KIC) and [U-14C]leucine were made into the left or right ventricles of sheep and pigs. Blood was sampled from the opposite ventricle. In both species, left ventricular infusions resulted in significantly lower specific radioactivities (SA) of [14C]leucine and [3H]KIC. [14C]KIC SA was found to be insensitive to infusion and sampling sites. [14C]KIC was in addition found to be equal to the SA of [14C]leucine only during the left heart infusions. Therefore [14C]KIC SA was used as the only estimate for [14C]SA in the equations for the two-pool model. This model eliminated the influence of site of infusion and blood sampling on the estimates for leucine entry and reduced the impact on the estimates for proteolysis and oxidation. This two-pool model could not compensate for the underestimation of transamination reactions occurring during the traditional venous isotope infusion and arterial blood sampling.
Effect of vasopressin blockade on blood pressure during water deprivation in intact and baroreceptor-denervated conscious dogs
Authors: Gregory L. C. , Quillen E. W. , Keil L. C. , Chang D. , Reid I. A.
Published: December 2017

Previous studies have provided evidence that vasopressin plays an important role in blood pressure regulation during water deprivation. However, these investigations have been complicated by reflex compensatory increases in cardiac output and renin secretion. The aim of the present study was to investigate the effect of blockade of the vasoconstrictor action of vasopressin in conscious water-deprived dogs in which the low- and/or high-pressure baroreceptors were denervated to minimize reflex responses. Vasopressin blockade in sham-operated dogs (n = 7) did not change arterial pressure. Heart rate rose from 78 +/- 9 to 119 +/- 13 beats/min (P less than 0.01), and plasma renin activity increased from 10.9 +/- 2.1 to 21.6 +/- 4.6 ng.ml-1.3 h-1 (P less than 0.01). In carotid sinus-denervated dogs (n = 6), vasopressin blockade again failed to decrease arterial pressure. Heart rate increased from 105 +/- 10 to 132 +/- 10 beats/min (P less than 0.01), and plasma renin activity rose from 6.8 +/- 1.7 to 15.5 +/- 2.4 ng.ml-1.3 h-1 (P less than 0.01). The antagonist also failed to change blood pressure in cardiac-denervated dogs (n = 5). Heart rate increased from 111 +/- 9 to 119 +/- 1 beats/min (P less than 0.01), but plasma renin activity did not increase significantly. In marked contrast, vasopressin blockade in sinoaortic/cardiac-denervated dogs (n = 7) promptly decreased arterial pressure from 115 +/- 8 to 94 +/- 7 mmHg (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of corticotropin-releasing factor on food intake and brown adipose tissue thermogenesis in rats
Authors: Arase K. , York D. A. , Shimizu H. , Shargill N. , Bray G. A.
Published: December 2017

Corticotropin-releasing factor (CRF) has been administered into the third ventricle of rats in acute and chronic experiments. Following a single 5-micrograms injection of CRF, there was an acute reduction in food intake at 30 and 60 min that was no longer significant at 3 h. Guanosine 5'-diphosphate (GDP) binding to mitochondria from interscapular brown adipose tissue (IBAT) of 21-h deprived rats was significantly increased 30 min after the acute infusion of 5 micrograms of CRF. Serum corticosterone was elevated in both groups but was significantly higher in the group treated with CRF. Serum glucose was unchanged. During a 7-day infusion of CRF (4.8 micrograms/day) into the third ventricle, the treated animals showed a slight, but significant, decrease in food intake but a progressive decline in body weight of 53 g over 7 days. Mitochondrial GDP binding was increased in the ad libitum-fed rats chronically treated with CRF. Serum corticosterone levels, although significantly higher than controls, were lower than following acute administration of CRF. These data show that CRF can acutely reduce food intake and increase sympathetic activity and that chronically it reduces body weight and may increase sympathetic activity without any consistent decrease in food intake.
Adrenalectomy eliminates both fiber-type differences and starvation effects on denervated muscle
Authors: Almon R. R. , Dubois D. C.
Published: December 2017

This report describes changes in muscle mass of innervated and denervated pairs of muscles taken from intact and adrenalectomized 250-g male Sprague-Dawley rats provided with different diets. Diets ranged from a nutritionally complete liquid diet to starvation (water only). In the intact animals, muscles with a more tonic character (soleus) are less sensitive to starvation than are muscles with a more phasic character (extensor digitorum longus), whereas the opposite is true of denervation. In the intact animals, starvation greatly increased the amount of atrophy following denervation. In the adrenalectomized animals, starvation had no effect on the amounts of atrophy following denervation. Furthermore, adrenalectomy virtually eliminated the fiber-type differences in the amount of atrophy following denervation. In addition, a comparison between denervated muscles from intact animals and adrenalectomized animals subjected to starvation demonstrates that all denervated muscles from the adrenalectomized animals atrophy less. Finally, it was observed that although an adrenalectomized animal can tolerate 6 days of starvation, an adrenalectomized-castrated animal cannot tolerate even short periods of starvation. The difference appears to be due to low amounts of corticosterone of testicular origin.
Sepsis-induced changes in in vivo insulin action in diabetic rats
Authors: Lang C. H. , Dobrescu C.
Published: December 2017

The present study examined whether sepsis exacerbates the diabetes-induced peripheral and hepatic insulin resistance. Vascular catheters were placed in diabetic (70 mg/kg streptozotocin, 4-wk duration) and nondiabetic rats, and sepsis was produced by subcutaneous injections of live Escherichia coli. Basal glucose metabolism was determined with the use of [3-3H]glucose initiated 18 h after the first injection of bacteria. Thereafter, in vivo insulin action was assessed with the use of the euglycemic hyperinsulinemic clamp technique. Sepsis in nondiabetic rats produced a 57% reduction in the maximal responsiveness for the insulin-induced increase in total glucose utilization compared with nondiabetic nonseptic animals. Diabetes alone decreased both insulin sensitivity and responsiveness. When the septic insult was superimposed on the diabetic condition, the maximum responsiveness was unchanged compared with non-septic diabetic rats, but the 50% maximally efficient dose was reduced from 817 to 190 microU/ml, suggesting an improvement in insulin sensitivity. Sepsis did not alter the insulin-induced suppression of hepatic glucose output in either nondiabetic or diabetic animals. Sepsis increased the plasma concentrations of epinephrine, norepinephrine, glucagon, and corticosterone in both nondiabetic and diabetic rats; however, the elevation in catecholamines and glucagon was 65 to 250% greater in the diabetic animals. These results indicate that hypermetabolic sepsis produces peripheral insulin resistance in nondiabetic rats but does not worsen the preexisting insulin resistance in diabetic animals, despite the higher prevailing blood levels of glucagon and catecholamines.
Fiber-type composition of nine rat muscles. I. Changes during the first year of life
Authors: Maltin C. A. , Delday M. I. , Baillie A. G. , Grubb D. A. , Garlick P. J.
Published: December 2017

There are few data available that describe the changes in fiber-type profiles with age in a range of muscles; thus fiber-type profiles and areas were determined in nine muscles of female rats from weaning to 1 yr. The results not only demonstrated the difference in fiber-type composition, size, and hence functional area in the various muscles examined but also illustrated the changes in these parameters with age. In particular, it was clear that two ends of a spectrum of fiber compositions are represented in the muscles studied: tensor fasciae latae, mainly fast-twitch glycolytic at one end and soleus (and adductor longus), mainly slow-twitch oxidative at the other; the remaining muscles were mostly dominated by fast-twitch fibers of a variety of metabolic types. Aging resulted in an increase in fiber area that was most dramatic in fast-twitch glycolytic fibers. Changes in fiber type with age were noted in all muscles, but the exact nature of the developmental changes appeared muscle specific.
Capsaicin-sensitive nerves are required for glucostasis but not for catecholamine output during hypoglycemia in rats
Authors: Zhou X. F. , Jhamandas K. H. , Livett B. G.
Published: December 2017

We have studied the glucose response and catecholamine (CA) response to insulin in the conscious rat to evaluate the role of sensory fibers in these responses in animals pretreated with capsaicin as neonates. In contrast to previous results obtained in anesthetized rats (Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 370: 201-215, 1986; Z. Khalil, B.G. Livett, and P.D. Marley. J. Physiol. Lond. 391: 511-526, 1987.), in conscious rats, insulin (1 IU/kg iv) produced only a mild hypoglycemia, which quickly returned to resting levels and caused no significant changes in plasma epinephrine levels. Somatostatin and SMS-(201-995), a somatostatin analogue, both potentiated and prolonged the insulin-induced hypoglycemia, resulting in an increase in circulating CA levels that was suppressed by hexamethonium and atropine. In capsaicin-pretreated rats the blood glucose levels at 90 min after insulin were significantly lower than those in vehicle-pretreated rats both in the presence (1 IU/kg insulin, 48 +/- 6 vs. 92 +/- 6 mg/100 ml, P less than 0.01) and absence (10 IU/kg insulin, 38 +/- 4 vs. 51 +/- 2 mg/100 ml, P less than 0.01) of SMS-(201-995). The CA levels in capsaicin-pretreated rats at 90 min after insulin were higher than in vehicle-pretreated rats (epinephrine levels: 27 +/- 4 vs. 10 +/- 1 pmol/ml in 1 IU/kg insulin, P less than 0.01; 64 +/- 14 vs. 25 +/- 5 pmol/ml in 10 IU/kg insulin, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanism for acute reduction of 1,5-anhydroglucitol in rats treated with diabetogenic agents
Authors: Yamanouchi T. , Akaoka I. , Akanuma Y. , Akanuma H. , Miyashita E.
Published: December 2017

The mechanism for acute reduction of plasma 1,5-anhydroglucitol (AG) in experimental diabetic rats was studied. Acute AG decrease was induced not only by diabetogenic agents, such as streptozotocin (STZ) and alloxan, but also by phloridzin, which caused glucosuria but not hyperglycemia. A similar reduction also occurred in hyperglycemia induced by glucose injection. The AG reduction induced by STZ was completely abolished by bilateral nephrectomy or by euglycemia with insulin treatment. The decrease of plasma AG was well correlated with the degree of urinary excretion of AG, which in turn reflected the degree of urinary glucose excretion, irrespective of the kind of agent causing the glucosuria. Under conditions of continuous glucose infusion, AG concentration decreased not only in plasma but also in various tissues and organs. The amount of AG lost was estimated to be almost equal to that excreted into urine during the period of infusion. These observations suggest that the degree of reduction of plasma AG depends simply on the urinary excretion of glucose, and it was assumed that the urinary excretion of 0.5 mg AG corresponds to the urinary excretion of 100 mg glucose during a short period after the onset of glucosuria.
Loss of abdominal fat and metabolic response to exercise training in obese women
Authors: Despres J. P. , Pouliot M. C. , Moorjani S. , Nadeau A. , Tremblay A. , Lupien P. J. , Theriault G. , Bouchard C.
Published: December 2017

Numerous studies have shown that a high accumulation of abdominal fat is associated with metabolic complications and with an increased risk of coronary heart disease. The present study examined the effects of changes in body fatness and in the level of abdominal fat on metabolic variables in a sample of 13 obese premenopausal women, aged 38.8 +/- 5.3 (SD) yr. Women exercised for 90 min at approximately 55% of maximal aerobic power (VO2 max) four to five times a week for a period of 14 mo. The training program induced a significant increase in VO2 max and a mean reduction in body fat mass of 4.6 kg (P less than 0.01), with no change in fat-free mass. Measurement of adipose tissue areas by computed tomography indicated a greater loss of abdominal fat compared with midthigh adipose tissue (P less than 0.05). The training program also produced significant reductions in the insulinogenic index measured during an oral glucose tolerance test and in plasma cholesterol (Chol), low-density lipoprotein (LDL)-Chol, and apolipoprotein (apo) B levels (P less than 0.05). Training also significantly increased plasma high-density lipoprotein (HDL)-apo A-I and HDL2-Chol levels and decreased plasma HDL3-Chol concentration (P less than 0.05). Whereas no change in postheparin plasma lipoprotein lipase activity was noted, a significant decrease in postheparin plasma hepatic triglyceride lipase activity was observed after training (P less than 0.005). Metabolic responses were not correlated with changes in VO2 max but were significantly correlated with the reduction in body fat mass and/or with the loss of deep abdominal fat.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of fatty acids on ammonia and amino acid flux from active human muscle
Authors: Graham T. E. , Kiens B. , Hargreaves M. , Richter E. A.
Published: December 2017

This study examined the dynamics of ammonia and amino acid exchange of human muscle during prolonged steady-state one-legged exercise at 80% of knee extensor maximal work capacity. Subjects (n = 10) performed leg extensor exercise for 1 h (control series), rested for 40 min while an infusion of Intralipid and heparin was begun, and then exercised the contralateral leg with the identical protocol [free fatty acid (FFA) series]. In the control series, ammonia efflux rose progressively, and 4.4 +/- 0.6 mmol were released in 1 h compared with 2.4 +/- 0.5 mmol (P less than 0.05) in the FFA series. The exercise was associated with large effluxes of total amino acids from the active muscle over the hour (12.8 +/- 4.3 and 10.3 +/- 3.3 mmol for control and FFA, respectively). Glutamine and alanine accounted for 47 and 64% of the efflux for the control and FFA series, respectively, while comparable values for essential amino acids were 24 and 20%. The latter implies that a net muscle protein catabolism was occurring during the exercise. The FFA treatment was associated not only with a reduced muscle ammonia release but also with a decreased (P less than 0.05) arterial concentration of nine amino acids (alanine, methionine, lysine, hydroxyproline, serine, glycine, proline, asparagine, and ornithine). Interpretation is limited due to the treatment order effect, but these data are compatible with the hypothesis that plasma clearance was affected by FFA.
Atrial natriuretic factor reduces renin release by opposing alpha-adrenoceptor activity
Authors: Naess P. A. , Christensen G. , Kiil F.
Published: December 2017

To examine how atrial natriuretic factor (ANF) inhibits renin release during renal sympathetic nerve stimulation, experiments were performed in barbiturate-anesthetized dogs. In five dogs, intravenous ANF infusion (50 ng.min-1.kg body wt-1) reduced renin release induced by renal nerve stimulation (1 Hz) from 16.8 +/- 8.4 to 3.5 +/- 2.1 micrograms angiotensin I (ANG I)/min. In two groups, renin release was raised by ureteral occlusion, which enhances the effects of beta-adrenoceptor stimulation and increased prostaglandin synthesis. During ureteral occlusion, intrarenal infusion of isoproterenol (0.2 micrograms.min-1.kg body wt-1) increased renin release in eight dogs to 82.6 +/- 10.9 micrograms ANG I/min, which was not significantly reduced by ANF infusion (81.1 +/- 10.1 micrograms ANG I/min). Similarly, intrarenal infusion of arachidonic acid (80 micrograms.min-1.kg body wt-1) during ureteral occlusion increased renin release in five dogs to 22.2 +/- 3.0 micrograms ANG I/min, which was not significantly reduced by ANF infusion (22.5 +/- 3.5 micrograms ANG I/min). Finally, in six dogs examined at free urine flow, intrarenal infusion of phenylephrine, an alpha-adrenergic agonist, raised renin release from 0.5 +/- 0.3 to 20.1 +/- 6.8 micrograms ANG I/min, which was reduced to 10.6 +/- 3.9 micrograms ANG I/min by intravenous ANF infusion (100 ng.min-1.kg body wt-1). These results indicate that ANF does not counteract stimulation of renin release by beta-adrenoceptors and prostaglandins but reduces nerve-stimulated renin release by opposing alpha-adrenoceptor activity.
Defective response to cAMP-dependent protein kinase in non-insulin-dependent diabetic heart
Authors: Schaffer S. W. , Allo S. , Punna S. , White T.
Published: December 2017

Hearts isolated from 1-yr-old non-insulin-dependent diabetic rats exhibited reduced responsiveness to the beta-adrenergic agonist isoproterenol. Over a concentration range of 3 x 10(-9) to 10(-7) M, isoproterenol-mediated stimulation in the rate of left ventricular pressure decline, a measure of myocardial relaxation, and the rate of left ventricular pressure rise, a measure of myocardial contractility, were significantly depressed in the diabetic hearts. To clarify the basis for this defect, individual steps involved in the actions of the beta-adrenergic agonists were examined. Dihydroalprenolol binding assays revealed that neither beta-adrenergic receptor number nor binding affinity was affected by the diabetic condition. Also unaffected by diabetes was isoproterenol-mediated stimulation of adenylate cyclase activity, myocyte accumulation of adenosine 3',5'-cyclic monophosphate (cAMP), or the increase in cAMP-dependent protein kinase activity ratio. However, it was found that both in the presence and absence of cAMP-dependent protein kinase, activity of the sarcolemmal calcium transporter was significantly depressed in the diabetic heart. Also attenuated was protein kinase-induced enhancement of sarcoplasmic reticular calcium transport. The likelihood that these abnormalities contribute to alterations in calcium homeostasis and myocardial contractile function is discussed.
Maintenance of thyroid hormone production during exercise-induced weight loss
Authors: Katzeff H. L. , Selgrad C.
Published: December 2017

Calorie restriction reduces thyroxine (T4) and 3,5,3'-triiodothyronine (T3) production, but the effects of exercise-induced weight loss on thyroid hormone metabolism in rodents are unclear. We studied the effects of chronic exercise on T4 and T3 metabolism comparing exercising (exercise) rats pair fed to sedentary (control) rodents and to weight-matched underfed sedentary animals (underfed; caloric intake 75% of ad libitum-fed controls). The exercise group utilized voluntary running wheels (28 days), and thyroid hormone metabolism was assessed using a three-compartment kinetics model. The exercise and underfed groups were equivalent in weight, but protein mass was greater in the exercise vs. underfed groups (30.4 +/- 0.5 vs. 27.9 +/- 0.5 g; P less than 0.05). During exercise, the T4 plasma clearance rate (PCR) was decreased (-39.2%; P less than 0.01) and the T4 concentration in serum was increased (48.6%; P less than 0.01), resulting in an unchanged T4 plasma appearance rate (PAR) vs. the control group. The decrease in T4 PCR in the exercise group was associated with a lower transport rate of T4 out of the slow pool (P less than 0.01). In the underfed group there was a reduction in both T4 serum concentration and PAR (-36%; P less than 0.01) compared with the control group, which was associated with a decrease in the volume of distribution (-25%; P less than 0.01). T3 PAR decreased 38.7% (P less than 0.01) during underfeeding but only 16.9% (P = not significant) during exercise vs. the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Proteolysis in skeletal muscle and whole body in response to euglycemic hyperinsulinemia in normal adults
Authors: Denne S. C. , Liechty E. A. , Liu Y. M. , Brechtel G. , Baron A. D.
Published: December 2017

To simultaneously assess the relative antiproteolytic effect of insulin on both skeletal muscle and in the whole body, phenylalanine rates of appearance (Ra; reflecting proteolysis) were measured across the leg (reflecting skeletal muscle) and in the whole body, utilizing a constant tracer infusion of [2H5]phenylalanine in the basal state and during euglycemic hyperinsulinemia (2,600 microU/ml) in seven normal adults. Phenylalanine Ra in the leg was significantly decreased during hyperinsulinemia (6.11 +/- 0.83 vs 3.59 +/- 0.70 mumol/min, P less than 0.001). In contrast, leg phenylalanine rate of utilization (Rd) was not significantly changed (4.88 +/- 0.77 vs. 3.86 +/- 0.92 mumol/min). Phenylalanine Ra in the whole body was significantly decreased during hyperinsulinemia (49.4 +/- 2.2 vs. 41.9 +/- 2.3 mumol/min, P less than 0.001). However, phenylalanine release was suppressed to a significantly greater degree in release was suppressed to a significantly greater degree in the leg than in the whole body during hyperinsulinemia (43 +/- 7 vs. 15 +/- 2%, P less than 0.01). These results suggest that insulin suppresses proteolysis in the whole body and in skeletal muscle, even in the face of hypoaminoacidemia. In addition, the substantially greater degree of suppression of proteolysis by insulin in skeletal muscle compared with the whole body suggests that, at least under these conditions, insulin may have a greater antiproteolytic effect on skeletal muscle compared with other tissues.
Effects of an opiate receptor antagonist on renin release in dogs
Authors: Johnson M. D. , Cavender R. K.
Published: December 2017

The present experiments were designed to determine whether blockade of endogenous opiate receptors with naloxone would suppress renin release induced by circulating epinephrine or by reductions of renal perfusion pressure. In the first series of experiments, anesthetized dogs were prepared with a flow probe around the left renal artery and a catheter in the left renal vein, permitting measurement of renin secretion before, during, and after 15-min infusions of epinephrine (50 ng.kg-1.min-1 iv). The epinephrine infusions were conducted either before or after blockade of opiate receptors with naloxone (1 mg/kg iv). Naloxone failed to alter the renin secretory response to intravenous epinephrine infusion. In a second series of experiments, anesthetized dogs were uninephrectomized and prepared with a constrictor cuff around the left renal artery and a renal arterial catheter distal to the cuff. After control measurements of renal perfusion pressure and plasma renin activity (PRA), the cuff was constricted at 15-min intervals to produce controlled stepwise reductions of renal perfusion pressure ranging from 15 to 90 mmHg. One-half of the animals was pretreated with naloxone (1 mg/kg iv). Naloxone pretreatment had no effect on the PRA response to reduced renal perfusion pressure at any pressure. The data fail to support the hypothesis that endogenous opioid peptides are modulators in the control of renin release.
Effect of osmolality on cytosolic free calcium and aldosterone secretion
Authors: Wang W. , Hayama N. , Robinson T. V. , Kramer R. E. , Schneider E. G.
Published: December 2017

Alterations in extracellular osmolality have powerful inverse effects on basal and potassium- and angiotensin-stimulated aldosterone secretion. With the use of bovine glomerulosa cells grown in primary culture, the effects of alterations in osmolality on cytosolic calcium concentration ([Ca2+]c), efflux and uptake of 45Ca2+, and aldosterone secretion were determined. Alterations in osmolality, independent of sodium concentration, have inverse effects on aldosterone secretion, which are correlated with simultaneous changes in [Ca2+]c measured using fura-2. Reductions in osmolality cause dose-dependent biphasic increases in [Ca2+]c different from the monophasic increases in [Ca2+]c produced by increases in potassium concentration. Like potassium- and angiotensin-stimulated increases in [Ca2+]c, hypotonically induced increases in [Ca2+]c are associated with an increase in 45Ca2+efflux. Reductions in osmolality also increased the uptake of 45Ca2+, an effect apparent at 2 min and persistent for at least 30 min. In the absence of extracellular calcium, reductions in osmolality, as increases in potassium concentration but not angiotensin, fail to increase [Ca2+]c, efflux of 45Ca2+, or aldosterone secretion. In conclusion, osmolality-induced alterations in aldosterone secretion are associated with parallel changes in [Ca2+]c, effects caused by alteration in the influx of extracellular calcium. On the basis of these and previous studies, we hypothesize that osmolality affects calcium influx by activating voltage-dependent or stretch-activated calcium channels.
Effect of acute food restriction on pulmonary growth and protein turnover in preterm guinea pigs
Authors: Kelly F. J. , Fussell J. C. , Postle T. D.
Published: December 2017

The effects of food restriction on the growth and protein turnover of the immature lung were investigated. Preterm guinea pigs, delivered by cesarean section at 65 days gestation (term = 68 days), were given free access to a lactating dam or restricted from feeding for 48 h. Food restriction resulted in significantly reduced body and lung (P less than 0.05) weight compared with fed controls. The rate of pulmonary protein synthesis determined in vivo was reduced by 33% in the food-restricted pups (28.9 +/- 10.2 vs. 19.4 +/- 4.5%, P less than 0.05 for control and food-restricted pups, respectively), whereas the calculated rate of protein breakdown remained unchanged. The inhibition of protein synthesis was accounted for by a 36% decrease in ribosomal efficiency (11.03 +/- 2.61 vs. 7.04 +/- 1.26%, P less than 0.01 for control and food-restricted pups, respectively), whereas ribosomal capacity was unaltered. Polyribosomal analysis indicated an increase in the proportion of RNA present in polysomes and a fall in the free monomer pool (26%), suggesting that food restriction blocked translation by reducing the rate of peptide chain elongation. This finding was confirmed by the analysis of ribosome transit times, which indicated a significant increase in the elongation rate in the lungs from food-restricted pups (0.51 +/- 0.11 vs. 0.94 +/- 0.19 min, P less than 0.05 for control and food-restricted pups, respectively). These results imply that nutrient supply plays an important role in protein deposition and hence growth and repair capacity of the immature lung.
Endothelin stimulates protein synthesis in smooth muscle cells
Authors: Chua B. H. , Krebs C. J. , Chua C. C. , Diglio C. A.
Published: December 2017

The present work was carried out to assess the effect of endothelin on the relative synthesis of protein, RNA, and DNA in confluent rat aortic smooth muscle cells (SMC) derived from Wistar-Kyoto (WKY) rats maintained under serum-free medium in the presence or absence of insulin, transferrin, and selenium. Insulin stimulated protein synthesis by 42%. Endothelin (1 x 10(-7) M) rapidly induced protein synthesis by 22% (-insulin) and 30% (+insulin). Prior treatment of SMC for 4 h with endothelin resulted in 50% (-insulin) and 38% (+insulin) increase in protein synthesis. The stimulatory effect of endothelin on protein synthesis could be partially blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a protein kinase C inhibitor. Atrial natriuretic factor had no effect on either the basal protein synthesis or protein synthesis stimulated by endothelin. Furthermore, endothelin stimulated RNA synthesis by twofold but had no effect on DNA synthesis in SMC derived from WKY rats. In contrast, SMC derived from spontaneously hypertensive rats showed increased DNA synthesis and cell growth after endothelin stimulation. These studies show that this hormone may play a pivotal role in the development of vascular hypertrophy in hypertension.
Corticosteroid receptors and lymphocyte subsets in mononuclear leukocytes in aging
Authors: Armanini D. , Karbowiak I. , Scali M. , Orlandini E. , Zampollo V. , Vittadello G.
Published: December 2017

Plasma cortisol and aldosterone levels and number of related receptors in mononuclear leukocytes were measured in 49 healthy aged subjects (62-97 yr) and in 21 adult controls (21-50 yr). In all subjects, in addition, lymphocyte subsets were determined as an index of corticosteroid action. The mean number of type I and type II receptors was significantly lower in aged subjects than in controls (respectively, 198 +/- 96 and 272 +/- 97 receptors/cell for type I, and 1,794 +/- 803 and 3,339 +/- 918 for type II receptors). Plasma aldosterone and cortisol and lymphocyte subsets were not different in the two groups. All of the parameters were also tested for correlation, and a significant inverse correlation was found between age and type I and type II receptors when all subjects were plotted and between aged and CD4 and age and CD4/CD8 in the aged group. These data show that aged subjects have reductions of corticosteroid receptors that are not associated with increase of related steroids and that this situation probably represents a concomitant of the normal aging process.
Oscillations of lactate released from islets of Langerhans: evidence for oscillatory glycolysis in beta-cells
Authors: Chou H. F. , Berman N. , Ipp E.
Published: December 2017

Oscillations in the glycolytic process have been demonstrated in a number of different biological systems. However, their presence has never been demonstrated in insulin-secreting beta-cells. We used lactate as a marker for glycolysis and measured lactate and insulin concentrations in the effluent of isolated perifused rat islets of Langerhans. Sustained regular oscillations in lactate concentrations with an average period of 16-20 min were observed in islets that were perifused with medium containing 5.5 or 16.7 mM glucose. Sustained oscillations of insulin concentrations secreted by the islets were also observed in these experiments, and the average period of oscillation was 14.6 +/- 2.3 min at 16.7 mM glucose. Mean insulin concentrations at 5.5 mM glucose were too low to permit analysis of oscillations. Spectral analysis confirmed the regularity of the lactate and insulin oscillations and showed peaks that were consistent with the average periods obtained using the Clifton program. Moreover, spectral analysis demonstrated marked similarity between the patterns of lactate and insulin oscillation during perifusion with 16.7 mM glucose. Cross-correlation analysis found these oscillations not to be consistently in phase. In conclusion, sustained oscillations in lactate released from islets of Langerhans suggest that the glycolytic process in beta-cells also oscillates. The similarity of the periods of lactate and insulin raises the possibility that oscillations in glycolysis may provide a mechanism for pulsatile insulin secretion.