bluuebunny/crossref_metadata_2025 huggingface dataset:
Aminoisobutyric acid transport in soleus muscles of lean and gold thioglucose-obese mice
Authors: Le Marchand-Brustel Y. , Moutard N. , Freychet P.
Published: December 2017

The uptake of alpha-aminoisobutyric acid (AIB) was studied in soleus muscles isolated from lean and gold thioglucose-lesioned obese mice (GTG-obese), both in basal and in insulin-stimulated conditions. The basal (i.e., non-insulin-stimulated) influx of AIB was decreased in muscles of GTG-obese mice because of a decrease in the apparent Vmax of the transport system. In muscles from both types of mice, insulin stimulated AIB influx by increasing the apparent Vmax of transport; this effect was partially dependent on new protein synthesis. In muscles of GTG-obese mice, the effect of insulin was altered in two ways: the absolute value of the maximally insulin-stimulated AIB influx was lower than in muscles of lean controls, and the dose response of insulin-stimulated AIB influx was shifted to the right (half-maximally effective concentration, EC50 congruent to 1.7 nM) compared to that observed in muscles of lean animals (EC50 congruent to 0.7 nM). It is concluded that in muscles of obese mice a) amino acid transport per se is altered, and b) the sensitivity of this process to the stimulatory effect of insulin is markedly diminished.
Insulin binding and action on fat cells from young healthy females and males
Authors: Pedersen O. , Hjollund E. , Lindskov H. O.
Published: December 2017

Insulin binding and action were studied in fat cells from the gluteal region of young healthy subjects. Fat cells from females were larger than those of males, had higher insulin receptor binding and higher rates of noninsulin-stimulated and maximally insulin-stimulated rates of methylglucose transport and glucose metabolism when these data were expressed per cell number. However, when insulin binding and insulin effects were expressed per cell surface, which may be physiologically more relevant, no sex differences were found in insulin binding and glucose transport, whereas noninsulin-stimulated and maximally insulin-stimulated glucose metabolism was still significantly increased in female fat cells. The latter indicates postreceptor differences in glucose metabolism between females and males. The insulin concentrations causing half-maximal responses (a measure of the sensitivity to insulin) of glucose transport, glucose metabolism and lipolysis were similar in fat cells from the two sexes, which is consistent with the comparable values of insulin receptor binding when adjusted to cell surface. Studies of rate-determining steps for the glucose utilization of human fat cells showed that glucose transport was not the rate-limiting step at physiological glucose concentrations. Moreover, at physiological glucose levels, glucose metabolism exhibited a decreased maximal insulin responsiveness and an increased insulin sensitivity when compared with glucose metabolism at low glucose concentrations at which glucose transport is rate limiting for the fat cell glucose utilization.
Central control of peripheral circulating somatostatin in dogs: effect of 2-deoxyglucose
Authors: Ipp E. , Piran U. , Richter H. , Garberoglio C. , Moossa A. , Rubenstein A. H.
Published: December 2017

Circulating plasma somatostatin concentrations are known to fluctuate in response to nutrients and hormones. However, little is known about neural or central nervous system (CNS) control of somatostatin secretion. To test whether peripheral circulating somatostatin is influenced by a central stimulus, 2-deoxyglucose (37.5 mg/kg) was infused into a lateral cerebral ventricle of six conscious dogs over a period of 15 min. Plasma somatostatin levels rose from a base line of 105 +/- 6 pg/ml (mean +/- SE) to a peak of 154 +/- 10 pg/ml (P less than 0.005) at 30 min after the onset of the infusion. Somatostatin levels were still significantly elevated (P less than 0.025) at 60 min (119 +/- 6 pg/ml) and thereafter gradually returned toward base line. Plasma glucose and glucagon levels increased in response to intraventricular 2-deoxyglucose. Glucose concentrations rose from 105 +/- 5 mg/dl to peak at 203 +/- 16 mg/dl (P less than 0.005) at 80 min and remained elevated to 120 min. The concentration of plasma glucagon increased from 41 +/- 6 to 92 +/- 18 pg/ml at 60 min (P less than 0.05) and then declined. In marked contrast to intraventricular 2-deoxyglucose, similar concentrations of 2-deoxyglucose administered intravenously (n = 4) resulted in a slight fall in plasma somatostatin. Intraventricular saline did not result in a change in plasma somatostatin. It is concluded that peripheral circulating somatostatin may be susceptible to central nervous system control.
Protein wasting due to acidosis of prolonged fasting
Authors: Hannaford M. C. , Leiter L. A. , Josse R. G. , Goldstein M. B. , Marliss E. B. , Halperin M. L.
Published: December 2017

During a total fast in obese subjects, the daily rate of nitrogen excretion undergoes only a small further decline after 2 wk, the excretion rate being about 5 g N/day. At this time, ammonium and urea each constitute about one-half of this excretion. The purpose of this study was to consider two alternative hypotheses: first, that the near plateau in nitrogen excretion represents an irreducible minimum rate of net protein breakdown in order to supply essential organs with calories in the form of glucose; second, that protein breakdown could be further reduced by minimizing the requirement to provide nitrogen for ammonium excretion during the ketoacidosis of fasting. Because ammonium excretion is largely controlled by acid-base balance, 150 mmol of sodium bicarbonate plus 60 mmol of potassium chloride were administered daily to decrease ammonium excretion in eight obese subjects who were totally fasting for more than 14 days. Urine ammonium nitrogen fell with this treatment (from 3.8 +/- 0.4 to 2.0 +/- 0.4 g N/g creatinine). In addition, there was a smaller fall in the rate of urea excretion (from 2.5 +/- 0.2 to 2.1 +/- 0.3 g N/g creatinine) together with a fall in the blood urea nitrogen. Therefore, it appears that ammonium excretion contributes to the negative nitrogen balance of a prolonged total fast, as assessed over a 3-day period of observation, is responsible for about one-third of the net lean body mass loss.
Central infusion of vasopressin decreased plasma vasopressin concentration in dogs
Authors: Wang B. C. , Share L. , Crofton J. T.
Published: December 2017

The effects of increasing the cerebrospinal fluid (CSF) vasopressin concentration (CSFADH) by intracerebroventricular infusion of vasopressin on the plasma vasopressin concentration (PADH) were studied in four groups of anesthetized dogs. One group received an intracerebroventricular infusion of artificial CSF (ACSF) alone for 90 min; the other groups were infused intracerebroventricularly with vasopressin at rates of 10, 20, or 50 microunits/min for 90 min. Arterial blood and CSF samples were taken just before infusion and at 30-min intervals for 210 min. Vasopressin infused intracerebroventricularly at 10, 20, and 50 microunits/min resulted in peak CSFADH of 32.2 +/- 5.3, 82.6 +/- 4.5, and 131.4 +/- 12.5 microunits/ml and reductions in PADH of 32, 47, and 51%, respectively. Only the latter two responses were significant (P less than 0.5-0.01). Because the peak increases in CSFADH after intracerebroventricular infusion of vasopressin ranged from values that were similar to or five times higher than those seen after severe hemorrhage or intracerebroventricular hypertonic saline infusion, we suggest that centrally acting vasopressin may play a physiological role in control of vasopressin secretion.
Circadian properties of vasopressin and melatonin rhythms in cat cerebrospinal fluid
Authors: Reppert S. M. , Coleman R. J. , Heath H. W. , Keutmann H. T.
Published: December 2017

Using a method for continuous removal of cisternal cerebrospinal fluid (CSF) from freely moving cats, we delineated the circadian nature of the daily rhythm in CSF arginine vasopressin. The daily melatonin rhythm was also monitored in CSF as another marker of circadian function. Under diurnal lighting conditions, both hormones exhibited prominent daily rhythms; the CSF vasopressin rhythm was characterized by high daytime values, whereas the CSF melatonin rhythm was characterized by high nighttime levels. In contrast, drinking behavior exhibited a 24-h component in only one of four animals studied. Daily CSF rhythms of vasopressin and melatonin persisted for over 78 days of study in constant light. The vasopressin rhythm clearly free-ran in this environment, manifesting cycle lengths of slightly greater than 24 h. The daily melatonin pattern split into several components with increasing time in constant light. An acute 8-h phase delay in the daily light-dark cycle resulted in corresponding but gradual phase shifts in both rhythms. These results indicate that both the vasopressin and melatonin rhythms in cat CSF are endogenously generated and are entrained by the daily light-dark cycle.
Energy expenditure in obesity in fasting and postprandial state
Authors: Felig P. , Cunningham J. , Levitt M. , Hendler R. , Nadel E.
Published: December 2017

Resting metabolic rate (RMR) was determined in 10 obese and 10 nonobese women after an overnight fast and for 3 h after the ingestion of an 800-kcal liquid meal. In the fasting state, absolute energy expenditure in the obese (4.8 +/- 0.2 kJ/min) was 25% greater than in the nonobese (P less than 0.005), but was comparable with the nonobese when expressed in relation to body surface area or lean body mass and was reduced by 20% when expressed per kilogram body weight3/4 (P less than 0.005). Meal ingestion resulted in a 14-16% increase in RMR (postprandial thermogenesis) that was similar in the two groups, so that absolute energy expenditure in the obese remained 22-25% higher than in the nonobese throughout the postprandial period. The estimated overall (fasting and postprandial) increase in resting caloric expenditure in the obese as compared with the nonobese was 350-375 kcal/day.
Sites of action of testosterone and estradiol on longitudinal bone growth
Authors: Jansson J. O. , Eden S. , Isaksson O.
Published: December 2017

In this study the mechanisms by which sex steroids influence body growth were investigated. The effect of different doses of testosterone propionate on longitudinal bone growth and body weight gain was studied in a) gonadectomized male rats, b) gonadohypophysectomized male rats, and c) gonadohypophysectomized male rats given replacement therapy with bovine growth hormone (bGH). The effect of different doses of estradiol benzoate on the same growth parameters was studied in female rats divided into the same experimental groups as the males. Accumulated longitudinal bone growth was determined using oxytetracycline as an intravital marker. Testosterone caused a dose-dependent increase in longitudinal bone growth in gonadectomized male rats. In contrast, testosterone exerted no significant increase in longitudinal bone growth in gonadohypophysectomized male rats with and without bGH replacement therapy. Treatment with estrogen inhibited longitudinal bone growth and body weight gain. The inhibitory effect of estradiol was approximately the same in gonadohypophysectomized female rats given bGH replacement therapy as in gonadectomized female rats. The results suggest that testosterone exerts its stimulatory effect on body growth mainly by modulating hypothalamopituitary functions, e.g., by altering the secretory pattern of GH. On the other hand, it seems that changes in the hypothalamopituitary functions are less significant for the inhibitory effect of estradiol on body growth. It is concluded from this study that the sites of action for estrogen and testosterone in modulating body growth in the rat are different.
Glucocorticoids and appearance of 1,25-dihydroxyvitamin D3 receptor in rat intestine
Authors: Massaro E. R. , Simpson R. U. , DeLuca H. F.
Published: December 2017

The ontogenesis of the 1,25-dihydroxyvitamin D3 specific binding activity in intestine was examined in vitamin D-deficient and replete rats. The absence of binding activity in intestines during the first two postnatal weeks was not influenced by vitamin D supplementation. The concentration of binding sites peaked on day 18 in vitamin D-replete rats and preceded that in the deficient group by approximately 1 wk. The influence of glucocorticoids on 1,25-dihydroxyvitamin D3-binding protein levels was examined by sequential hydrocortisone administration and adrenalectomy. Subcutaneous hydrocortisone administration before day 14 postpartum did not induce binding activity. The concentration of binding sites was significantly increased to 369 +/- 60 fmol/mg of protein by hydrocortisone injections from days 15 to 17 postpartum when compared with an average of 182 +/- 16 fmol/mg of protein in littermate controls. Hydrocortisone administration did not further increase receptor levels in rats injected from days 19 to 21. Bilateral adrenalectomy on day 17 postpartum significantly decreased the concentration of binding sites. It is concluded that adrenal glucocorticoids play an important role in the developmental appearance of 1,25-dihydroxyvitamin D3 specific binding activity in the postnatal rat intestine.
Nature of calcemic effect of 1,25-dihydroxyvitamin D3 in experimental hypoparathyroidism
Authors: Hefti E. , Trechsel U. , Fleisch H. , Bonjour J. P.
Published: December 2017

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] treatment on the daily fluctuation of plasma calcium concentration ( [Ca]P1) in relation to the feeding-fasting alternation has been studied in vitamin D-replete sham-operated (sham) and thyroparathyroidectomized (TPTX) rats fed a normal Ca diet. 1,25(OH)2D3 was given (26 or 39 pmol/day) intraperitoneally either by single injection or constant infusion using osmotic minipumps. After 7 days of treatment [Ca]P1 was measured at 4-h intervals for 24 h. Pair-fed, sham and TPTX animals received the solvent vehicle intraperitoneally. The results show that in sham rats the very moderate daily fluctuation of [Ca]P1 was not accentuated by 1,25(OH)2D3. A marked fluctuation of [Ca]P1 in relation to the food intake was observed in untreated TPTX as compared with sham rats. In TPTX rats 1,25(OH)2D3 increased the fasting [Ca]P1. In contrast the rise in [Ca]P1 during feeding was not significantly accentuated by 1,25(OH)2D3. The daily fluctuation of [Ca]P1 was the same whether the dose of 1,25(OH)2D3 was given in one single injection or by constant infusion, suggesting that this hormone is not involved in the hour-to-hour regulation of [Ca]P1. In conclusion, in the absence of parathyroid glands, 1,25(OH)2D3 given in doses that stimulate intestinal calcium absorption has a much more pronounced effect on the fasting calcemia than on the rise in calcemia observed during the feeding period. These results suggest that the mobilization of calcium from bone could play an important role in the calcemic effect of 1,25(OH)2D3 when given in the hypoparathyroid state.
Hyperinsulinemia of preobese and obese fa/fa rats is partly vagus nerve mediated
Authors: Rohner-Jeanrenaud F. , Hochstrasser A. C. , Jeanrenaud B.
Published: December 2017

In vivo glucose-induced insulin secretion was greater in preweaned preobese 17-day-old Zucker rats than in the corresponding controls. This hypersecretion of insulin was reversed to normal by acute pretreatment with atropine. A short-lived (30 s) electrical stimulation of the vagus nerve preceding a glucose load potentiated the in vivo glucose-induced insulin release in adult animals (6-9 wk) and more so in obese Zucker (fa/fa) than in lean rats. This suggested the existence of enhanced sensitivity and/or responsiveness of the B cells of obese animals to the parasympathetic system. That the parasympathetic tone was increased in adult obese Zucker (fa/fa) rats was corroborated by the observation that acute vagotomy of these animals resulted in a significant decrease in glucose-induced insulin secretion, whereas no such effect was seen in lean rats. Also, perfused pancreases from adult obese (fa/fa) rats oversecreted insulin during a stimulation by arginine when compared with controls, an oversecretion that was restored toward normal by superimposed infusion of atropine. It is concluded that a) the increased insulin secretion of preobese Zucker fa/fa rats is an early abnormality that is mediated by the vagus nerve, and b) increased secretion of insulin in adult obese fa/fa rats continues to be partly vagus-nerve mediated, although a decreased sympathetic tone and other unknown defects could conceivably play a role as well.
Enhanced responsiveness to insulin in sheep exposed to cold
Authors: Weekes T. E. , Sasaki Y. , Tsuda T.
Published: December 2017

The effects of cold exposure on tissue sensitivity and responsiveness to insulin were determined by the euglycemic insulin clamp technique. Insulin was infused at rates of 0.2, 0.5, 1.0, 6.0, and 30.0 mU x kg-1 x min-1 into five adult sheep in a warm environment and after cold exposure (0 degree C) from 7 to 23 days. Cold exposure increased basal plasma glucose concentration and basal glucose irreversible loss. Glucose metabolic clearance rate (MCR) was significantly increased by cold exposure at all rates of insulin infusion, with increases ranging from 44 to 72%. The insulin concentration causing half-maximal stimulation of glucose MCR was unchanged by environment (warm, 42 microU/ml; cold, 36 microU/ml). Combined alpha + beta-adrenergic blockade did not affect the increased response to insulin during cold exposure. Endogenous (hepatic) glucose production was inhibited by insulin to a similar extent in the two environments and was less sensitive to insulin than was glucose utilization or MCR. The results suggest that cold exposure increases the responsiveness to insulin of a postreceptor event in peripheral tissues.
Insulin binding to microvascular endothelium of intact heart: a kinetic and morphometric analysis
Authors: Bar R. S. , DeRose A. , Sandra A. , Peacock M. L. , Owen W. G.
Published: December 2017

We have studied insulin binding to blood vessels of the intact, beating heart. The beating hearts were perfused with [125I]iodoinsulin (3 X 10(-10) M) followed by perfusion with unlabeled insulin. The unlabeled insulin displaced the bound [125I]iodoinsulin in direct proportion to the concentration of the unlabeled hormone. Perfusion with unlabeled insulin at 10(-11) M elicited a significant displacement of [125I]iodoinsulin, with a maximal effect at 10(-6) M. Unlabeled proinsulin also displaced [125I]iodoinsulin in a dose-dependent manner, being 1% as potent as insulin. Perfusion with unrelated peptides had no effect. Radioautographic counting of 125I grains indicated that greater than 95% of the grain counts over blood vessels were within the microvessels. When [125I]iodoinsulin perfusion was followed by perfusion with unlabeled insulin at 10(-6) M, there was a 50% decrease in grain counts over the microvessels (versus perfusion with [125I]iodoinsulin alone); with coperfusion of [125I]iodoinsulin and 10(-6) M unlabeled insulin, an 80% decrease in grain counts occurred. Electron microscopic radioautography indicated that the 125I grains were associated with the vascular endothelial cells. We conclude that specific insulin receptors are present on endothelial cells of microvessels in the intact heart.
Brown adipose tissue of mice with gold thioglucose-induced obesity: effect of cold and diet
Authors: Hogan S. , Himms-Hagen J.
Published: December 2017

Gold thioglucose (GTG)-obese mice have a larger than normal amount of brown adipose tissue (BAT) with ultrastructurally normal mitochondria. The tissue grows normally when the mice adapt to cafeteria feeding or to cold (8 degrees C). Acute exposure to cold causes a fairly normal thermogenic activation of BAT mitochondria of GTG-obese mice, both in dynamic and static phases of their obesity. However, chow-fed GTG-obese mice have BAT mitochondria that are in a low state of thermogenic activation, and these mice fail to respond to eating a cafeteria diet for 3 wk by a normal thermogenic activation of their BAT mitochondria. More prolonged cafeteria feeding for 11-13 wk, into the static phase of obesity, is associated with thermogenic activation of BAT mitochondria of GTG-obese mice. The capacity of GTG-obese mice to respond to noradrenaline (norepinephrine) by an increase in metabolic rate is greater than that of lean mice and is further enhanced by cold acclimation. It is concluded that BAT of the GTG-obese mouse is inherently functional, as is control of its thermogenic function and growth during cold exposure and cold acclimation. Dietary influences on BAT thermogenic function are, however, defective in the GTG-obese mouse at least during the dynamic phase of its obesity. The resulting failure of diet-induced thermogenesis would be expected to contribute to the known high metabolic efficiency of the GTG-obese mouse and, together with the hyperphagia, to the obesity induced by GTG.
Failure of somatostatin to modify effect of glucagon on carbohydrate metabolism in the dog
Authors: Cherrington A. D. , Lacy W. W. , Williams P. E. , Steiner K. E.
Published: December 2017

Somatostatin is widely used to inhibit insulin and glucagon release by the pancreas in studies of metabolic regulation in vivo. To determine whether the peptide can directly modify the metabolic effects of an increment in glucagon in overnight-fasted conscious dogs, glucagon was increased in the presence (+S) or absence (-S) of somatostatin. Either somatostatin (+S; 0.8 microgram . kg-1 . min-1) or a two-stage pancreatectomy (-S) was used to inhibit the endocrine pancreas, and at the same time replacement infusions of insulin (285-300 microU . kg-1 .min-1) and glucagon (0.65 ng . kg-1 . min-1) were given. After a 40-min control period the plasma glucagon level was raised fourfold in the presence of fixed basal insulin. Plasma insulin in both groups were similar [11 +/- 2 (+S) and 9 +/- 1 (-S) microU/ml]. Glucagon rose from 64 +/- 11 to 225 +/- 19 and 92 +/- 11 to 219 +/- 20 pg/ml in the +S and -S groups, respectively. Tracer-determined ([3-3H]glucose) glucose production rose by 5.28 +/- 1.02 (+S) and 4.25 +/- 1.12 (-S) mg . kg-1 . min-1 at 15 min and fell similarly over 3 h in both groups. Plasma glucose rose similarly in both groups peaking at 195 +/- 15 (+S) and 174 +/- 8 (-S) mg/dl. Plasma alanine fell similarly over 3 h [133 +/- 35 (+S) and 138 +/- 42 (-S) mumol/liter]. Conversion of [14C]alanine and [14C]-lactate to [14C]glucose rose progressively over 3 h in both groups, eventually being elevated by 210 +/- 58 (+S) and 148 +/- 48% (-S). We conclude that in the dog somatostatin at the dose used does not alter the effect of an increment in glucagon on carbohydrate metabolism.
Three types of alpha-melanocyte-stimulating hormone: bioactivities and half-lives
Authors: Rudman D. , Hollins B. M. , Kutner M. H. , Moffitt S. D. , Lynn M. J.
Published: December 2017

Three types of alpha-melanocyte-stimulating hormone (alpha MSH) that differ in the acetyl status of the N-terminal serine have been found in the neurointermediate lobe of the pituitary gland and in the brain: desacetyl alpha MSH, which lacks an acetyl group; monoacetyl alpha MSH, in which the amino group of the serine is acetylated; and diacetyl alpha MSH, in which both amino and hydroxy groups of the serine are acetylated. We compared the lipolytic and melanotropic actions of these three peptides, and their rates of disappearance from plasma, both in vitro and in vivo. The following differences were found. a) For in vitro lipolytic actions on rabbit adipose tissue slices, the potencies differed according to the order diacetyl = monoacetyl greater than desacetyl. On rabbit isolated adipocytes, however, the three peptides were equipotent. b) For in vivo lipolytic action in the rabbit, not only potency but also kinetics differed. Diacetyl alpha MSH had the slowest onset, longest duration, and greatest potency. The desacetyl variant had the quickest onset, shortest duration, and least potency. c) The half-life for elimination from rabbit plasma both in vitro and in vivo was shortest for the desacetyl form and longest for the diacetyl peptide. d) For in vitro melanotropic effect on frog skin, kinetics of action were the same for all three peptides, but potency differed according to the order diacetyl = monoacetyl greater than desacetyl. Thus acetylation of alpha MSH alters lipolytic and melanotropic potencies in vitro and lipolytic potency and kinetics in vivo. These differences result in part from the fact that acetylation slows the degradation of the tridecapeptide both inside and outside the circulation.
Metabolic effects of dichloroacetate in diabetic dogs
Authors: Park R. , Radosevich P. R. , Leach W. J. , Seto P. , Arieff A. I.
Published: December 2017

In fasted, diabetic dogs treated with dichloroacetate (DCA) (300 mg X kg-1 X h-1 iv), we determined the relative contributions by skeletal muscle and gut to the supply of precursors used for hepatic gluconeogenesis. The total production of lactate and alanine by skeletal muscle and gut decreased from 2,370 to 1,160 mumol X kg-1 X h-1 during treatment with DCA. Hepatic uptake of these substrates decreased from 1,040 to 435 mumol X kg-1 X h-1, and blood glucose decreased from 370 +/- 18 to 279 +/- 22 mg/dl (P less than 0.001). DCA treatment decreased the skeletal muscle production of both lactate and alanine to 40% of control, whereas gut production was decreased to only 72% of control levels. Hepatic uptake of the two substrates decreased in proportion to the change in blood levels because fractional hepatic extraction was unaltered. The effects of DCA on the interorgan metabolism of plasma amino acids showed that diminished availability of alanine for hepatic gluconeogenesis was compensated in part by increased release of other gluconeogenic amino acids from muscle and gut. Gut uptake of glutamine appeared unchanged, but most of its metabolic end products were released in greater amounts by DCA treatment, suggesting enhanced glutamine degradation. These results in fasted, diabetic dogs indicate that 1) DCA treatment lowers blood glucose in part by limitation of gluconeogenic substrate supply from skeletal muscle and gut, and 2) DCA has complex and diverse effects on the interorgan metabolism of plasma amino acids.
Iodothyronine homeostasis in rat brain during hypo- and hyperthyroidism
Authors: Dratman M. B. , Crutchfield F. L. , Gordon J. T. , Jennings A. S.
Published: December 2017

Thyroid hormones are concentrated, retained, and metabolized in discrete neural systems in rat brain. To determine how iodothyronine requirements of brain compare with those of other thyroid hormone-dependent tissues, we measured effects of chronic thyroid hormone deficiency or excess on brain iodothyronine economy and particularly on the intracerebral rate of triiodothyronine formation from thyroxine. The results demonstrate that despite extremes of thyroxine availability, brain thyroxine and triiodothyronine concentrations and brain triiodothyronine production and turnover rates are kept within narrow limits. Adjustments in the activity of both brain and liver help to maintain these relatively stable conditions. Following thyroidectomy, fractional rates of triiodothyronine formation from thyroxine decrease to low levels in liver, whereas they increase markedly in brain; exactly the opposite direction of change occurs in brain and liver during hyperthyroidism. These responses suggest that brain iodothyronine homeostasis is important for the function of the whole organism. Because signs of nervous system dysfunction develop in hypothyroid and hyperthyroid individuals, it is possible that even relatively small deviations of brain iodocompound economy can produce significant changes in behavior and autonomic nervous system function.
Regulation of conversion of thyroxine to triiodothyronine in perfused rat kidney
Authors: Ferguson D. C. , Jennings A. S.
Published: December 2017

The factors regulating the renal uptake of thyroxine (T4), its conversion to 3,5,3'-triiodothyronine (T3), and the urinary iodothyronine excretion were studied in the perfused rat kidney. Increasing the perfusate free T4 (FT4) concentration from 1 to 11.5 times that of euthyroid rat serum resulted in a linear increase in T4 uptake and T3 production that was not saturated at the highest dose. When FT4 concentrations were increased by decreasing the perfusate albumin concentration from 7.5 to 2.5 g/dl, T4 uptake and T3 production increased in proportion to the FT4 concentration. Propylthiouracil (PTU), a 5'-deiodinase inhibitor, decreased renal T3 production by 60.5% without affecting tissue T4 uptake. In the absence of glomerular filtration, T4 uptake and T3 production were unchanged, indicating that T4 is extracted by the contraluminal surface of the renal tubule. However, probenecid, an inhibitor of contraluminal organic acid uptake, did not decrease but increased T4 uptake and T3 production by increasing the perfusate FT4 fraction in the perfusate. There was no net renal 3,3',5'-triiodothyronine (rT3) production from T4, and degradation and urinary excretion of T3 were negligible. The urinary excretion of T4 and T3 correlated closely with the degree of proteinuria.
Hepatic mitochondrial function in lean and obese Zucker rats
Authors: Brady L. J. , Hoppel C. L.
Published: December 2017

Hepatic mitochondrial function was studied in lean and obese Zucker rats in the fed state and at 3 and 6 days of starvation. No significant differences in state 3 mitochondrial oxidative rates were found due to obesity or starvation. Palmitoylcarnitine utilization rates in mitochondria were unaffected by obesity or starvation; however, when expressed per gram liver weight, they were lower in the obese rats due to the decreased amount of mitochondrial protein per gram liver. For palmitoylcarnitine oxidation and acetoacetate and citrate production, the patterns were the same: per milligram mitochondrial protein, both lean and obese rates were equivalent; per total liver, the obese rates were higher; per gram liver, the obese rates were lower. Mitochondrial carnitine palmitoyltransferase specific activity was higher in fed obese than in lean rats and remained higher during starvation. The results indicate that mitochondrial capacity to oxidize fatty acids and to produce keto acids is not affected by genetic obesity or starvation. The differences in fatty acid oxidation and keto acid production that have been observed in hepatocytes and perfused liver might be explained by decreased mitochondrial protein per unit weight of liver or hepatocytes in obese rats.
Angiotensin-mediated calcium efflux from adrenal glomerulosa cells
Authors: Foster R. , Rasmussen H.
Published: December 2017

The effects of angiotensin II on efflux of radiocalcium and production of aldosterone from dispersed bovine adrenal glomerulosa cells were studied using a flow-through system. Concentrations of angiotensin II between 1.25 X 10(-10) and 1.25 X 10(-8) M were found to stimulate both radiocalcium efflux and the rate of aldosterone production. The increase in radiocalcium efflux occurred within 1.5-2.5 min after angiotensin addition, reached a peak in 3.0-4.5 min, and then declined to a value slightly greater than control. The initial increase in aldosterone production occurred 3-5 min after the peak of calcium efflux. In cells preloaded with [45Ca] and then perfused for 1 h with a medium containing no calcium, the basal rate of aldosterone production fell to zero. Angiotensin II (1.25 X 10(-8) M) caused no increase in aldosterone secretion rate but still caused an efflux of radiocalcium. Exposure of cells to 5 X 10(-5) M verapamil blocked the effect of 1.25 X 10(-10) M angiotensin on both radiocalcium efflux and aldosterone production, but only partially blocked the effects of 1.25 X 10(-8) M angiotensin. In addition to stimulating calcium uptake into adrenal glomerulosa cells, angiotensin II stimulates the mobilization of calcium from an intracellular pool. The precise location of this pool is not known.
Organ and plasma metabolism of neurotensin in sheep
Authors: Shulkes A. , Fletcher D. R. , Hardy K. J.
Published: December 2017

The metabolism of neurotensin (NT) across specific vascular beds of conscious sheep and the stability of NT in plasma have been quantitated. The nature of the metabolites has been characterized with region-specific antiserums and chromatography. NT-(1-13) was infused at 200 pmol X kg-1 X h-1 for 60 min into nine ewes, and blood samples were taken via cannulas in the aorta, pulmonary artery, portal vein, hepatic vein, renal vein, and jugular vein. Two antiserums, one directed towards the N-terminal end of NT (7852) and the other directed to the C-terminal end (C28) were used for radioimmunoassay. Pancreatic polypeptide (PP) was measured also. Using the steady-state concentrations in the aorta, the metabolic clearance rate of NT measured with C28 was 25.8 +/- 3.2 ml X kg-1 X min-1, twice that with 7852. The kidney, brain, and gut were the major organs clearing NT with a greater disappearance of C-terminal than N-terminal immunoreactivity. Gel chromatography of plasma at steady state showed that the NT immunoreactivity consisted of intact NT and N-terminal fragments; no C-terminal fragments were detected. Similarly, incubation of NT in plasma in vitro resulted in the generation of stable N-terminal fragments. The kidney was also the major organ involved in the clearance of PP both in the basal state and after stimulation by NT. Because the C-terminal end of NT is biologically active, these studies suggest that either N-terminal fragments have some unknown biological role or that NT is acting as a local hormone.
Evidence of a paracrine role for pancreatic somatostatin in vivo
Authors: Taborsky G. J.
Published: December 2017

Somatostatin (SS) in the D cells of the pancreatic islets has been hypothesized to tonically inhibit the secretion of glucagon and insulin from the neighboring A and B cells. To test this hypothesis directly, a nonimmunoreactive analogue of somatostatin [( D-Ala5-D-Trp8]SS) was infused intravenously at 0.55–17 micrograms/min into anesthetized dogs to suppress the secretion of pancreatic somatostatin and observe the effects of that suppression on glucagon and insulin release. Infusions of this analogue into anesthetized dogs at both a low dose (1.7 micrograms X min-1 X 30 min iv, n = 7) and at a medium dose (5.5 micrograms X min-1 X 30 min iv, n = 7) suppressed the release of somatostatin-like immunoreactivity (SLI) from the in situ canine pancreas by 31 +/- 10% of base line (P less than 0.025) and 45 +/- 6% of base line (P less than 0.0005), respectively. These doses increased glucagon secretion markedly (by 179 +/- 39 and 250 +/- 60% of base line, both P less than 0.005) and increased insulin secretion moderately (by 35 +/- 17 and 62 +/- 27% of base line, respectively, both P less than 0.05). The highest dose of analogue (17 micrograms/min, n = 9) produced less stimulation of glucagon release (delta = +95 +/- 35% of basal, P less than 0.025) and marked inhibition of insulin release (delta = -61 +/- 9% of basal, P less than 0.0005) despite a larger inhibition of pancreatic SLI release (delta = -84 +/- 3% of basal, P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
Pregnancy-induced insulin resistance in the rat: assessment by glucose clamp technique
Authors: Leturque A. , Burnol A. F. , Ferre P. , Girard J.
Published: December 2017

To quantify and characterize the insulin resistance during pregnancy in the rat, a euglycemic hyperinsulinemic clamp was set up. Dose-response curves for the effects of five concentrations of insulin on glucose production, glucose utilization, and glucose clearance were performed in age-matched virgin and 19-day-pregnant rats. Glucose production and glucose utilization were measured by using [3-3H]-glucose. Glucose production was totally suppressed at plasma insulin concentrations higher than 1,000 microU/ml in the two groups. Insulin concentration causing half-maximal suppression of glucose production was about 70 microU/ml in virgin rats and 250 microU/ml in pregnant rats. Maximal glucose utilization was obtained at plasma insulin concentrations of 2,000 microU/ml. In pregnant rats maximal increment in glucose utilization was significantly lower (P less than 0.01) than in virgin rats. Insulin concentrations causing half-maximal stimulation of glucose utilization were 200 microU/ml in virgin rats and 500 in pregnant rats. As blood glucose concentration in virgin and pregnant rats was clamped at, respectively, 0.97 +/- 0.03 and 0.73 +/- 0.03 mg/ml, glucose clearance rates were calculated because this parameter is minimally affected by the changes in blood glucose concentrations. A normal maximal increment in glucose clearance in response to insulin was restored in pregnant rats but the rightward shift of the dose-response curve was maintained. Plasma insulin concentrations necessary for half-maximal increment of glucose clearance in the two groups were similar to that observed when the results were expressed as glucose utilization. Thus, insulin resistance during late pregnancy in the rat is characterized by a decreased sensitivity of liver and peripheral tissues to insulin.
LH release is facilitated by agents that alter cyclic AMP-generating system
Authors: Cronin M. J. , Evans W. S. , Hewlett E. L. , Thorner M. O.
Published: December 2017

The issue of whether the adenosine 3',5'-monophosphate (cAMP)-generating system contributes to luteinizing hormone (LH) release was addressed by using several complementary probes in vitro. Pertussis toxin is considered to modify covalently an inhibitory adenylate cyclase regulatory protein. Treatment of gonadotrophs with this toxin increased both basal LH release and the efficacy of gonadotropin-releasing hormone (GnRH)-stimulated LH release with no apparent effect on GnRH potency. Cholera toxin, which probably activates adenylate cyclase by covalently altering another regulatory protein, forskolin, which directly stimulates the catalytic subunit of adenylate cyclase, and the cAMP analogue 8-Br-cAMP amplified both basal LH release (in a dose-dependent manner) and GnRH-stimulated LH release after a lag of 1 (cholera toxin and 8-Br-cAmP) and 4 (forskolin) h. It is noteworthy that these belated effects occurred in spite of the fact that cellular cAMP accumulation was markedly increased within 30 min after cholera toxin and at 1 min after forskolin addition. There was no change in total radioimmunoassayable LH (cellular + released) in either the basal or GnRH-treated cells after cholera toxin and forskolin for up to 24 h. Finally, the forskolin-amplified LH release was reversible and calcium dependent because D-600, EDTA, and calcium-free medium inhibited this effect. These results, generated with three complementary probes that affect integral proteins of the adenylate cyclase complex, suggest a function for cAMP in modulating LH release.
Hyperinsulinemia and in vivo very-low-density lipoprotein-triglyceride kinetics
Authors: Steiner G. , Haynes F. J. , Yoshino G. , Vranic M.
Published: December 2017

The effect of hyperinsulinemia (2 wk of twice daily NPH insulin) on the kinetics of very-low-density lipoprotein (VLDL)-triglyceride (TG) was studied in rats. To avoid profound hypoglycemia the rats were allowed sucrose ad libitum. Two control groups were needed: chow only and ad libitum sucrose-supplemented (high-CHO). The insulin-treated rats had 15 times higher IRI and 50% lower plasma glucose levels than either control group. Their TG production exceeded and their TG concentrations were less than those of either control group. This indicated that their TG removal was increased even more than their TG production. This increase in TG production occurred despite lower plasma free fatty acid (FFA) levels, suggesting that a greater proportion of TG fatty acids came from a source other than FFA. Compared with chow controls, high-CHO controls had the same peripheral IRI, a slight increase in TG production, and an increase in TG concentration. The differences between the effects of CHO supplementation alone or together with injected insulin may relate to the IRI and/or the route of access of insulin (peripheral vs. portal). The present studies indicate that hyperinsulinemia, either directly or indirectly, accelerates triglyceride turnover.
A maternal defect is responsible for growth failure in vitamin D-deficient rat pups
Authors: Brommage R. , DeLuca H. F.
Published: December 2017

Vitamin D deficiency was induced in lactating rats and their pups by placing female rats on a vitamin D-deficient diet immediately after mating. Evidence of vitamin D deficiency included undetectable plasma levels of 25-hydroxyvitamin D3 in the dams, maternal hypocalcemia, the lack of pup growth, and pup hypocalcemia following starvation. This method of producing vitamin D-deficient pups was then used to determine whether the failure of vitamin D-deficient pups to grow properly results from a maternal or neonatal defect. Vitamin D-deficient dams and pups were injected with either vitamin D3 or the ethanol vehicle, and pup growth was monitored over the subsequent 6 days. Providing vitamin D3 to the pups directly had no effect on their growth, but administering vitamin D3 to the dams resulted in a tripling of the pup growth rate. The failure of vitamin D3 to promote pup growth when given directly to the pups was not the result of their inability to metabolize the vitamin because these pups converted [3H]-vitamin D3 to 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3 as determined by comigration with standards on both straight and reverse phase high-performance liquid chromatography systems. These results demonstrate that a maternal defect is responsible for the growth failure observed in vitamin D-deficient rat pups.
Energy metabolism in rats with ventromedial hypothalamic lesions
Authors: Hustvedt B. E. , Jeszka J. , Christophersen A. , Lovo A.
Published: December 2017

Rats with ventromedial hypothalamic lesions (VMH) have increased ability to accumulate energy. The aim of this investigation was to characterize the main processes responsible for the reduced energy expenditure, using indirect calorimetry, nitrogen, and energy balance techniques. Metabolism was studied during different metabolic conditions created by a strict feeding regimen with concentrated feeding periods. A computerized system for indirect calorimetry enabled continuous study of individual animals for prolonged time periods. We found a mean decrease of 15.5% in total energy expenditure and decreased nitrogen retention in VMH rats. Calculation of respiratory quotient (RQ), energy expenditure, and the metabolic mixture demonstrated fluctuations in metabolism in accordance with the feeding regimen. The same percent reduction in resting postabsorptive energy expenditure was found as in total expenditure. Quantitatively, this main finding means that metabolic processes that occurred both in the resting and postabsorptive state were responsible for two-thirds of the total reduction in energy expenditure, whereas only one-third could be attributed to differences in dietary-induced thermogenesis and/or physical activity. It is concluded that VMH-animals spent as much as 10.3% of their total energy expenditure on liponeogenesis compared with 2.5% in controls.
Effect of sucrose feeding on alpha 1-adrenergic responses in rat liver
Authors: Lynch C. J. , Guarino J. J. , Deth R. C. , Steer M. L.
Published: December 2017

A sustained increase in sympathetic nervous system (SNS) activity was induced by substituting a 10% sucrose solution for the drinking water of rats fed laboratory chow ad libitum. The effects of increased SNS activity on alpha 1-adrenergic processes in liver were examined by evaluating three alpha 1-responses, namely, phenylephrine-stimulated ouabain-sensitive 86Rb+ uptake, 45Ca2+ efflux, and glucose release. Sucrose feeding abolished phenylephrine stimulation of ouabain-sensitive 86Rb+ uptake and 45Ca2+ efflux and induced a three- to fourfold reduction in the ability of phenylephrine to stimulate glucose release from liver slices. Pretreatment with 6-hydroxydopamine markedly reduced liver norepinephrine content. When 6-hydroxydopamine was used to prevent the sucrose-induced increase in SNS activity, the changes in 86Rb+ uptake, 45Ca2+ efflux, and glucose release that otherwise followed sucrose feeding were not observed. Sucrose feeding did not alter binding of the alpha 1-antagonist [3H]prazosin to liver cell membrane alpha 1-receptors or displacement of [3H]prazosin by the alpha-agonist epinephrine. These observations suggest that sustained increases in SNS activity may have profound effects on liver alpha 1-adrenergic events that occur subsequent to hormone-receptor interaction.
Sites of protein conservation and loss during starvation: influence of adiposity
Authors: Goodman M. N. , Lowell B. , Belur E. , Ruderman N. B.
Published: December 2017

Previous studies have established that older (16 wk) and more obese rats conserve body protein during prolonged starvation. This adaptation is due in part to a curtailment of muscle proteolysis. To determine whether this response occurs also in younger rats and whether protein is conserved at sites other than muscle, studies were conducted in young 6-wk-old rats previously fed either a chow or a high-fat diet before starvation. Fat feeding caused a marked increase in adipose mass and prolonged survival. Whereas chow-fed rats survived the fast for approximately 5 days, fat-fed rats lived for 10 days and diminished their excretion of nitrogen for at least 6 days, indicative of protein conservation. Despite the ability of fat-fed rats to survive the fast longer, protein was conserved in only a few organs. The timing and magnitude of protein loss from liver, kidney, intestine, and lung was similar to that in chow-fed rats, and little protein was lost during the fast from brain, stomach, skin, and soleus muscle in either group. In fat-fed rats, cardiac and skeletal muscle were the principle tissues in which protein was conserved, and this adaptation was lost when body fat stores were nearing exhaustion. In both groups nitrogen excreted in the urine early in the fast was derived mainly from protein lost from muscle, liver, and to a lesser extent intestine. Later in the fast, the principal source was muscle. These findings indicate that during starvation in the rat the conservation of protein occurs principally in skeletal and cardiac muscle. They also suggest that the ability of the rat to conserve protein is dependent on the size of its lipid stores.
Lactate and regulation of lung glycolytic rate
Authors: Fisher A. B. , Dodia C.
Published: December 2017

The effect of exogenous lactate on glycolytic rate was studied with the isolated perfused rat lung. Glucose utilization was estimated from the rate of 3H2O production from [5-3H]glucose, and lactate and pyruvate production was measured by perfusate assay. Glucose utilization was unaffected by addition of 0.5 mM lactate to the perfusate but decreased by 27% with 1 mM lactate. With 2 mM lactate, glucose utilization was decreased by 46% and lactate production decreased 95%. With addition of 0.2 mM pyruvate plus 2 mM lactate, glucose utilization was decreased 63% compared with control. These data indicate that the effect of lactate on glucose utilization was not through change in the cellular redox state. During lung anoxia produced by ventilation with CO, glucose utilization and lactate production were again markedly decreased by addition of lactate (2 mM) to the perfusate. However, addition of pyruvate plus lactate resulted in a markedly stimulated rate of glucose utilization. This result indicates that during anoxia the effect of lactate on glycolysis resulted from alteration of the redox ratio. This study indicates that lactate influences the rate of glycolysis in the normal lung through its utilization as a substrate for mitochondrial metabolism. During anoxia, changes in the lung redox state with lactate are a major determinant of the glycolytic rate.