bluuebunny/crossref_metadata_2025 huggingface dataset:
Arginine metabolism and urea synthesis in cultured rat skeletal muscle cells
Authors: Pardridge W. M. , Duducgian-Vartavarian L. , Casanello-Ertl D. , Jones M. R. , Kopple J. D.
Published: December 2017

Skeletal muscle is known to contain arginase, but, because this enzyme is also present in erythrocytes, the exact origin of arginine-derived ornithine in peripheral tissues is uncertain. In the present studies, skeletal muscle cells obtained from regenerating hindlimb muscle of adult rats were grown in primary tissue culture for approximately 3 wk and then studied in regard to changes in medium amino acid concentrations over a 48-h period. The consumption of arginine and serine was observed in parallel with the production of ornithine, proline, citrulline, glycine, and urea. Medium threonine and methionine concentrations were relatively constant over 48 h. Incubation of muscle cells with [U-14C]arginine resulted in the formation of [14C]ornithine and [14C]proline at rates at least 10-fold greater than could be accounted for by enzyme constituents of fetal calf serum. In addition, [guanido-14C]arginine was converted to [14C]urea and [U-14C]serine was converted to [14C]glycine. These studies indicate that cultured skeletal muscle cells contain a high arginase capacity and actively synthesize ornithine and urea from arginine.
Urinary excretion of arterial blood prostaglandins and thromboxanes in man
Authors: Zipser R. D. , Martin K.
Published: December 2017

To determine the fraction of the arterial prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and thromboxane B2 (TXB2) that is excreted unmetabolized into human urine, the 3H-labeled compounds were separately infused into the renal artery or brachial vein of 23 subjects. Urine extracts were subjected to sequential chromatography on thin-layer plates, Sephadex LH-20, and reverse-phase high-pressure liquid chromatography to isolate the unmetabolized fraction. Dual isotope ratio techniques were used to identify peak fractions, to assess purity, and to calculate recovery. Following renal artery infusions, 32.2% of 6-keto-PGF1 alpha, 13.5% of TXB2, and 3.9% of PGE2 were excreted unmetabolized. Calculated fractional excretion of these compounds on a single transit through the kidney are approximately 30, 13, and 3.9%, respectively. Following brachial vein infusion of [3H]prostaglandin I2, 2.7% of the infusate was excreted as 6-keto-PGF1 alpha, suggesting that circulating prostaglandin I2 may contribute to urinary 6-keto-PGF1 alpha. When combined with published measurements of urinary PGE2, 6-keto-PGF1 alpha, and TXB2, these data can be used to calculate the maximum arterial blood concentration of these substances. The results indicate that arterial blood concentration of PGE2, TXB2, and 6-keto-PGF1 alpha in man are only a few picograms per milliliter or less.
Calcitonin modulation of insulin and glucagon secretion in man
Authors: Giugliano D. , Passariello N. , Sgambato S. , Torella R. , D'Onofrio F.
Published: December 2017

These studies were undertaken to evaluate the effect of different doses of calcitonin on insulin and glucagon responses to intravenous glucase loads and to assess the mechanism/s by which calcitonin inhibits insulin secretion in man. In our studies, even the infusion of the 1-U dose of calcitonin was found to inhibit by 45% the acute insulin response to a glucose (20 g) pulse. This effect was associated with a significant decrease in glucose disappearance rates. These negative effects of calcitonin on both insulin secretion and glucose tolerance were dose-related. The inhibition of the acute insulin response to glucose was 65% and up to 90% with the infusion of the 4- and 8-U doses, respectively. The suppressive effect of glucose on glucagon secretion was significantly reduced by calcitonin. The inhibitory effect of calcitonin on insulin responses to glucose (5 g) and glucose tolerance was reversed by both theophylline and calcium. By contrast, infusion of lysine acetylsalicylate to block the synthesis of endogenous prostaglandins did not diminish the inhibitory effect of calcitonin on insulin secretion. These results demonstrate that a) calcitonin inhibits glucose-induced insulin responses and deteriorates glucose tolerance in normal humans in a dose-dependent manner; b) calcitonin reduces the suppressive effect of glucose on glucagon secretion in a dose-related fashion; and c) both theophylline and calcium reverse the inhibitory effect of calcitonin on insulin secretion. It is hypothesized that calcitonin effects on insulin and glucagon release are mediated via a change in calcium redistribution in the islet cells.
Free fatty acid mobilization in rats following intracerebroventricular norepinephrine
Authors: Barbosa M. C. , Migliorini R. H.
Published: December 2017

The possible involvement of central synaptic transmitters in lipomobilization was investigated by injecting norepinephrine or carbachol into the cerebrospinal fluid of conscious, unrestrained rats. Intracerebroventricular administration of minute amounts of norepinephrine (25-400 nmol in 5 microliters) induced a rapid increase in plasma free fatty acids (FFA) and glycerol. Small increases in blood sugar levels were induced only by the higher doses of norepinephrine. Plasma FFA response to the catecholamine was dose related in the range of 25-100 nmol of hormone. Previous intraventricular administration of propranolol, but not of phentolamine, completely blocked the lipomobilzing effect of intraventricular norepinephrine. In contrast to norepinephrine, carbachol (27 or 54 nmol) injected intraventricularly did not affect plasma FFA or glycerol levels, but markedly increased blood sugar levels. Increase of plasma FFA and glycerol by intraventricular norepinephrine and blockade of the response by propranolol suggest the involvement of a beta-adrenergic mechanism in the centrally mediated lipolysis activation. On the basis of these and previous results, it is hypothesized that central beta-adrenergic synapses relay impulses generated in receptors specifically involved in lipomobilization to the sympathetic fibers of adipose tissue.
Sham feeding-induced cephalic phase insulin release in the rat
Authors: Berthoud H. R. , Jeanrenaud B.
Published: December 2017

The effect of the cephalic phase of food ingestion on plasma insulin and glucagon concentration was assessed in the sham-feeding rat, bearing chronically implanted gastric drainage fistulas. It was found that continuous sham feeding produced a significant and phasic peripheral insulin response in the absence of any significant changes of glycemia. The response was almost completely blocked by prior intravenous administration of 2 mg/kg of atropine methyl nitrate and potentiated by prior intravenous administration of 1.0 or 2.5 mg/kg of phentolamine. In spite of the larger insulin response after phentolamine, there was no hypoglycemia detected. Furthermore, continuous sham feeding did not produce a significant glucagon response, whereas real feeling did. The results demonstrate that cholinergic insulin release is triggered phasically by continuous ingestion of familiar food and that this insulin response is inhibited by an alpha-adrenergic sympathetic tone. It is further concluded that the increased glucose disposal produced by the neurally released insulin is not counteracted by a concomitant glucagon response or by direct adrenergic stimulation of hepatic glucose production.
Measurement of blood flow in pancreatic islets of the rat: effect of isoproterenol and norepinephrine
Authors: Meyer H. H. , Vetterlein F. , Schmidt G. , Hasselblatt A.
Published: December 2017

Blood flow to the pancreatic islets of the anesthetized rat has been measured by application of microspheres, intravital staining of the endocrine tissue by Dithizon, and induction of organ transparency by incubation in glycerol. Thus the microspheres could be counted separately in the islet tissue and in the remaining organ. The total pancreatic blood flow in the rat amounted to 0.48 +/- 0.04 ml.min-1.g-1 and the flow fraction of the islet tissue to 1.22 +/- 0.09%, corresponding to a flow rate through the pancreatic islets of 5.42 +/- 0.63 microliters/min. When isoproterenol was applied (0.1 and 1.0 micrograms.kg-1.min-1 iv for 15 min), total pancreatic blood flow rose to 0.60 +/- 0.08 and 0.98 +/- 0.10 (P less than 0.01) ml.min-1.g-1, whereas the flow fraction to the islets decreased to 0.82 +/- 0.08 (P less than 0.01) and 0.61 +/- 0.07% (P less than 0.01). The absolute islet perfusion remained nearly unchanged. Norepinephrine (2.0 and 5.0 micrograms.kg-1.min-1 for 15 min) similarly increased total blood flow to 0.78 +/- 0.08 (P less than 0.01) and 0.64 +/- 0.08 ml.min-1.g-1) while reducing the islet flow fraction to 1.15 +/- 0.13 and 0.83 +/- 0.05% (P less than 0.01). The absolute flow rate through the islet tissue did not change significantly. The conclusion may be drawn from these experiments that changes in total pancreatic blood flow are not necessarily accompanied by corresponding changes in the perfusion rate of the endocrine islet tissue.
Metabolic response of normal man and insulin-infused diabetics to postprandial exercise
Authors: Nelson J. D. , Poussier P. , Marliss E. B. , Albisser A. M. , Zinman B.
Published: December 2017

Physical exercise is often performed during absorption of meals. We have characterized the metabolic response to 45 min of moderate exercise (approximately 55% of estimated maximal oxygen uptake) beginning 30 min after breakfast in seven healthy controls. Nine insulin-dependent diabetes were studied in an identical manner, with glycemia controlled by a closed-loop "artificial endocrine pancreas" controlled by a closed-loop "artificial endocrine pancreas" (AEP). Responses were compared to those during breakfast without exercise. In the controls, onset of exercise rapidly reversed the rise in both glycemia and insulin (IRI) that occurred with breakfast alone, both returning to fasting levels (glycemia, 80 +/- 3 mg/dl; IRI, 0.38 +/- 0.10 ng/ml). After exercise, small and transient increments occurred (glycemia, 33 +/- 6 mg/dl; IRI, 0.81 +/- 0.15 ng/ml). In the diabetics, prior overnight intravenous insulin normalized fasting glycemia (98 +/- 4 mg/dl), and its postbreakfast excursion was identical to that of controls, as were those of most measured substrates. Similarly, with exercise, glycemia returned rapidly to fasting levels, accompanied by an appropriate decrease in insulin infusion rates. "Free" IRI levels mirrored changes in infusion rates by the AEP, with a decrease in insulin requirement of 30% during exercise as compared to breakfast alone (P less than 0.05). Thus, in both diabetics treated with the AEP and in normals, the responses to postprandial exercise required rapid modulation of insulin delivery. To demonstrate the effect of postprandial exercise on preprogrammed open-loop insulin replacement, four diabetic subjects were studied during breakfast with and without exercise while receiving a fixed open-loop insulin infusion pattern (6.1 +/- 0.7 U over 140 +/- 8 min). The glycemic response to breakfast alone was entirely normalized. However, symptomatic hypoglycemia occurred in all subjects when exercise was initiated 30 min after breakfast. The diabetic responses to closed-loop insulin infusion provide important data in defining the appropriate preprogrammed open-loop insulin infusion pattern for postprandial exercise.
Modulation by adrenalectomy and fasting of insulin effects in perfused hindlimb muscle
Authors: Shikama H. , Chu D. T. , Exton J. H.
Published: December 2017

Perfused hindlimb muscle from fed adrenalectomized rats accumulated more 2-deoxyglucose at submaximal concentrations of insulin in comparison to muscle from fed normal rats. However, in the fasted state, insulin-stimulated 2-deoxyglucose uptake was largely inhibited by adrenalectomy. Basal 2-deoxyglucose uptake did not differ between fed and fasted normal or adrenalectomized rats. The changes in insulin effects caused by adrenalectomy were due to altered hexose transport as shown by measurements of 3-O-methylglucose uptake and of intracellular free and phosphorylated 2-deoxyglucose. Muscles of fasted normal and fed or fasted adrenalectomized rats showed higher basal glycogen synthase --glucose-6-P/+glucose-6-P activity ratios than those of fed normal rats probably because of decreased glycogen content. However, muscles from fed or fasted adrenalectomized rats did not show any alterations in insulin effects on the activity ratio and half-maximal activation constant (A0.5) for glucose-6-P of glycogen synthase. Because of the dissociation of the effects of insulin on hexose transport and glycogen synthase in muscle of fasted adrenalectomized rats, it is concluded that the impairment in insulin-stimulated hexose transport in these animals is due to a defect lying beyond the interaction of insulin with its receptor.
Brown adipose tissue hyperplasia: a fundamental mechanism of adaptation to cold and hyperphagia
Authors: Bukowiecki L. , Collet A. J. , Follea N. , Guay G. , Jahjah L.
Published: December 2017

Cold acclimation (4 degrees C) and "cafeteria diets" increased the thermic response of rats to catecholamines. This phenomenon was accompanied by six- to eightfold increases of interscapular brown adipose tissue (IBAT) weight, total tissue cytochrome oxidase activity, and total number of brown adipocytes. Quantitative radioautographic experiments using [3H]thymidine disclosed that cold exposure markedly enhanced the mitotic activity in blood capillaries and small-venule endothelial cells, adipose tissue interstitial cells, and preadipocytes rather than in fully differentiated brown adipocytes. IBAT mitotic index increased 70 times over control values after only 2 days of cold exposure. Thereafter, the proliferative activity progressively decreased. IBAT cell composition was modified during cold acclimation as the percentage of interstitial cells and preadipocytes increased over the other cellular types. Because brown adipose tissue is the principal site of norepinephrine-induced thermogenesis in homeothermal animals, it is suggested that brown adipocyte proliferation from precursor cells represents the fundamental phenomenon explaining the increased capacity of cold-acclimated animals to respond calorigenically to catecholamines.
Estradiol stimulation of LH response to LHRH and LHRH binding in pituitary cultures
Authors: Tang L. K. , Martellock A. C. , Horiuchi J. K.
Published: December 2017

The relationship between 17 beta-estradiol (E2) stimulation of luteinizing hormone (LH) response to LH-releasing hormone (LHRH) and E2 effect on LHRH binding was examined in pituitary monolayer cultures prepared from female rats. E2 pretreatment significantly (P less than 0.05) augmented the LHRH-induced LH release to 158-180% of the non-E2-treated controls. The maximal E2-priming effect could be observed after 1 day of treatment. E2 treatment for 3 days stimulated [D-Ala6]luteinizing hormone-releasing hormone (LHRHa) binding to about 1.5-fold that of the non-E2-treated controls without affecting the dissociation constant of LHRH receptor (Kd = 4 X 10(-10) M). The stimulatory effect of E2 on cell proliferation as determined by [3H]thymidine incorporation was also observed 3 days after treatment. However, E2 stimulation of LH accumulation in the cultured cells could be detected as early as 4 h after treatment. These results indicate that E2-priming effect on pituitary LH response to LHRH is initially associated with an increase in cellular LH content and later associated with increases in LHRH binding and in an index of cell proliferation that may include the LH-producing cells.
Acetylcholine receptor turnover in myasthenia gravis
Authors: Appel S. H. , Blosser J. C. , McManaman J. L. , Ashizawa T.
Published: December 2017

Humoral antibodies directed against the acetylcholine receptor are present in most patients with myasthenia gravis. These antibodies accelerate receptor degradation and thus cause a decrease in receptor level and impaired neuromuscular transmission. The stimulus that triggers and sustains the formation of the antibodies has not been identified, but it is possible that the primary antigen may be located on the cell surface of thymic lymphocytes. In some situations the clinical state in myasthenia gravis does not correlate with the antibody titer, suggesting that other factors also influence receptor amount and/or function of other potential regulators that have been investigated. Calcium and agents that increase cyclic AMP appear to increase the formation of the receptor and thus might serve to mitigate the effects of the circulating antibodies. In contrast, cholinergic agonists may cause a further decrease in receptor number, providing an explanation of why myasthenic patients may become resistant to therapy.
Deficiency of hormone receptor-adenylate cyclase coupling protein: basis for hormone resistance in pseudohypoparathyroidism
Authors: Spiegel A. M. , Levine M. A. , Aurbach G. D. , Downs R. W. , Marx S. J. , Lasker R. D. , Moses A. M. , Breslau N. A.
Published: December 2017

Pseudohypoparathyroidism is an inherited disorder associated with resistance to the action of several hormones, including parathyroid hormone, thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone. The disorders described under this designation are heterogeneous in regard to the underlying genetic defects, the phenotypic manifestation, and the severity of the defects in hormone action. The majority of affected individuals who also have the characteristic skeletal changes (heredity osteodystrophy) have a defect in the guanine nucleotide regulatory protein (G protein) that is essential for coupling certain cell-surface hormone receptors to the adenylate cyclase system. This defect is probably the cause for resistance to the action of multiple hormones. In the remaining patients the cause for hormone resistance has not been identified.
Clinical physiology of adrenergic receptor regulation
Authors: Lefkowitz R. J.
Published: December 2017

Radioligand binding studies now permit the direct investigation of the alpha- and beta-adrenergic receptors. The concentration of the receptors in cell membranes is modulated by a wide variety of physiological and pathophysiological variables and may be either increased or decreased in different conditions. Ligand binding techniques have also shed light on the ways in which the adrenergic receptors are coupled to other components of the hormone-sensitive adenylate cyclase system. This “coupling” is also a highly regulated step, control of which importantly influences catecholamine and sensitivity of tissues.
Effects of adrenalectomy and corticosterone administration on hypothalamic obesity in rats
Authors: Bruce B. K. , King B. M. , Phelps G. R. , Veitia M. C.
Published: December 2017

The present experiment was designed to assess the role of adrenal hormones in hypothalamic hyperphagia and obesity. Ventromedial hypothalamic (VMH) or sham lesions were produced either 15 days before or after adrenalectomy (ADX) or sham adrenalectomy in rats in a completely counterbalanced design (experiment 1). Body weight and food intake were recorded for 30 days after the second surgery. Adrenalectomy in obese VMH animals eliminated all excess weight gain and decreased food intake to below the level of all control groups. VMH lesions in ADX animals did not produce the characteristic weight gain associated with ventromedial hypothalamic damage, and this group was not significantly different from animals with sham lesions in body weight or food intake. In experiment 2, the administration of corticosterone resulted in a marked increase in the rate of weight gain in ADX-VMH animals, and the withdrawal of the hormones was followed by weight loss. It is concluded that adrenal glucocorticoid hormones are necessary for the development and maintenance of VMH hyperphagia and obesity.
Urinary excretion of acetylcarnitine during human diabetic and fasting ketosis
Authors: Hoppel C. L. , Genuth S. M.
Published: December 2017

The urinary excretion of acetylcarnitine was studied in patients with diabetic ketosis before and during insulin therapy and in normal-weight and obese subjects during fasting. In the diabetic ketotic patients, acetylcarnitine represented 61% of the total acylcarnitine excretion. During the first 24 h of insulin treatment, acetylcarnitine excretion decreased and on the 5th day of treatment was 18% of the acylcarnitines excreted. The urinary excretion of the other acylcarnitines fell slowly. In normal-weight subjects fasted for 3 days, the urinary excretion of acetylcarnitine increased on the 2nd day of fasting, and on the 3rd day acetylcarnitine accounted for 78% of the excreted acylcarnitine. In obese subjects there was a progressive increase in urinary acetylcarnitine excretion, but on day 6 it represented only 55% of the total acylcarnitine excreted. The urinary excretion of acetylcarnitine correlated with blood beta-hydroxybutyrate concentration in the normal-weight subjects during fasting and in the diabetic ketotic patients. Acetylcarnitine accounts for a major fraction of the acylcarnitines excreted in the three ketotic conditions studied. The contribution of acetylcarnitine to the change in acylcarnitines as ketosis appears or disappears is significantly less in the obese subjects than in the normal-weight subjects or in the diabetic patients. This difference may reflect an alteration in the production or disposition of acetyl-CoA and acetylcarnitine in obesity.
Effects of apoproteins C on lipoprotein lipase activity bound to rat fat cells
Authors: Verine A. , Salers P. , Boyer J.
Published: December 2017

During short-term incubation, a suspension of fat cells isolated from female rats hydrolyzed tri[3H]oleyl[14C]glycerol added as substrate and incorporated an average of 42% of the amounts of [3H]oleic acid released. Lipolysis was catalyzed by cell-bound lipoprotein lipase (LPL), whose activity was influenced by apoproteins (apo) C purified from human plasma. ApoC-II enhanced 12-fold the hydrolysis rates with cells from fed rats versus 3,4-fold with cells from fasted rats. In both cases, the stimulation by apoC-II was greater than that by whole serums from led or fasted rats. Maximal LPL activity at the cell surface depended more on the preexisting nutritional state of the cell than on apoC-II or serums added extracellular. ApoC-I, apoC-III1 and apoC-III2 had no or moderate direct effects on LPL activity, whereas apoC-III1 and apoC-III2 reduced markedly the stimulating effect of apoC-II. At all levels of LPL activity, the amounts of [3H]oleic acid liberated by hydrolysis and incorporated as [3H]acylglycerol in cell lipids were highly correlated with LPL activity, suggesting that the uptake process was directly related to enzyme action.
Catecholamine-thyroid hormone interaction on myocardial ornithine decarboxylase
Authors: Chideckel E. W. , Rosovski S. J. , Belur E. B.
Published: December 2017

Myocardial phosphorylase alpha activity responds to stimulation by catecholamines and thyroid hormone. In hyperthyroidism this enzyme is supersensitive to beta-adrenergic stimulation and blockade, indicating that its increased activity is an indirect effect of thyroid hormone. Myocardial ornithine decarboxylase (ODC) activity also responds to catecholamine and thyroid hormone stimulation. In the present studies, we sought to determine whether ODC shares the responses of phosphorylase alpha in hyperthyroidism. As opposed to euthyroid rats, isoproterenol acutely inhibited myocardial OCD activity in hyperthyroid rats. Timolol (60 mg/kg) injected immediately before the isoproterenol blocked this paradoxical inhibitory effect, defining it as beta-adrenergic. When timolol (100 mg/kg), distributed over a 24-h period, was administered during the 3 days of triiodothyronine (T3) administration, it blocked the T3 stimulation of myocardial OCD activity by 35%. However, timolol affected weight gain of the hyperthyroid rats. When fasted rats were used, timolol was without effect on T3-induced myocardial ODC stimulation. Timolol was also without effect on T3-induced stimulation of hepatic ODC or on T3-induced cardiomegaly. Timolol did decrease the T3-induced tachycardia. In summary, in the hyperthyroid heart, 1) isoproterenol paradoxically inhibits myocardial ODC activity and 2) timolol, when food intake is not a variable, is without effect. We conclude that the effect of thyroid hormone on myocardial ODC is not mediated by change in catecholamine sensitivity. Thus the behavior of phosphorylase alpha does not represent a general enzymatic phenomenon.
Effect of phenoxybenzamine on development of adipose tissue in lean and obese Zucker rats
Authors: Comai K. , Sullivan A. C.
Published: December 2017

Young male Zucker lean (Fa/-) and obese (fa/fa) rats were fed the alpha-adrenergic blocking agent phenoxybenzamine as a dietary admixture for 35 days. In lean and obese rats, phenoxybenzamine treatment decreased significantly body weight gain, food consumption, grams of carcass fat, and grams of carcass protein. Lean rats exhibited reduced fat cell size and number in retroperitoneal, epididymal, and inguinal fat depots. Obese rats treated with phenoxybenzamine exhibited significantly decreased numbers of fat cells in the retroperitoneal, epididymal, and inguinal fat depots and a small decreased cell size in the inguinal fat depot only. The levels of carcass fat and protein and fat cell number in obese and lean rats treated with phenoxybenzamine for 35 days were similar to pretreatment values in agreement with the lack of body weight gain. Although values in agreement with the lack of body weight gain. Although rats exhibited marked decreases in fat accumulation during phenoxybenzamine treatment, fat cell size and number returned to control values during the posttreatment period with a marked hyperplasia occurring particularly in the retroperitoneal fat depot of obese rats. Serum levels of insulin were suppressed and free fatty acid levels increased in obese rats during phenoxybenzamine treatment, suggesting a stimulation of the sympathoadrenal system. This study shows that despite severe restrictions in fat cell proliferation during the rapid-growth phase of the obese Zucker rat, the mechanisms for cellular proliferation and fat deposition remain intact.
Time course of effects of ovarian hormones on food intake and metabolism
Authors: Gray J. M. , Greenwood M. R.
Published: December 2017

The effects of administration of estradiol benzoate (EB) or EB plus progesterone (EB + Prog) on feeding behavior and lipid metabolism were examined in ovariectomized rats killed 1, 2, 3, 7, or 14 days after the onset of hormone treatment. EB caused a transient decrease in food intake and body weight gain and a sustained decrease in adipose tissue lipoprotein lipase activity, and progesterone attenuated this EB effect. Hepatic acetyl CoA carboxylase (ACC) and fatty acid synthetase (FAS) activities decreased in the first days of hormone treatment (both EB and EB + Prog treatments) and returned to normal at 1 wk in both treatment groups. At 2 wk, hepatic ACC and FAS activities were greatly elevated in the EB, but not the EB + Prog group. These data demonstrate the complexity of the patterns of behavioral and metabolic responses after ovarian hormone manipulation in adult female rats.
Foster mother rat entrains circadian adrenocortical rhythm in blinded pups
Authors: Takahashi K. , Hayafuji C. , Murakami N.
Published: December 2017

Free-running patterns of blood corticosterone rhythm were examined between the fourth and eighth postnatal week in blinded pups optically enucleated on day 1. When blinded pups were raised by intact natural mothers, the peak time of corticosterone rhythm appeared near the time of light-dark (LD) transition, which was close to that of mothers, and then free-ran. This phase relation between mothers and pups showed that mothers entrained pups' corticosterone rhythm. When blinded pups born of LD (or DL) mothers were raised by DL (or LD) foster mothers, the corticosterone rhythm in blinded pups was close to that of foster mothers at 4 wk of age, indicating that a foster mother plays a predominant role in entraining the pups' rhythm. When blinded pups were raised by blinded mothers whose rhythm was out of phase of the lighting cycle, pups' rhythm was in phase with that of mothers, showing that lighting cycle did not affect the pups' rhythm. These facts indicate that the mother nursing pups acts as the most predominant entrainer of corticosterone rhythm of the blinded pups.
Hepatic and renal metabolism of copper and zinc in the diabetic rat
Authors: Failla M. L. , Kiser R. A.
Published: December 2017

The influences of acute and chronic insulin-dependent diabetes on copper and zinc status of liver, kidney, and intestine were investigated in rats at 0-4 wk after streptozotocin (STZ) treatment. The concentration and the tissue contents of copper in liver and kidney were significantly elevated by 1 wk after STZ injection and increased thereafter, attaining levels two- and fivefold higher, respectively, than controls by 4 wk. Increased concentrations of zinc were also present in liver and kidney at 7 and 2 days after treatment, respectively, but zinc accumulated to a lesser degree than copper. In contrast, the concentration of copper and zinc in duodenum from control and all STZ-diabetic groups were similar. Increased and decreased quantities of copper and zinc were bound to metallothionein (MT) in liver and kidney, respectively, within 2 days after STZ injection. Thereafter, the quantities of both metals associated with MT increased with time in both tissues. Additional changes in zinc distribution in hepatic cytosol occurred prior to significant increases in the concentration of this metal in the tissue. The potential significance of altered trace metal metabolism during short-term changes in endocrine status and adverse effects of heavy metal accumulation during chronic hormonal imbalance are discussed.
Biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3
Authors: Okamoto S. , Tanaka Y. , DeLuca H. F. , Kobayashi Y. , Ikekawa N.
Published: December 2017

The biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3 was compared with 1,25-dihydroxyvitamin D3 in the rat. The 24,24-difluoro-1,25-dihydroxyvitamin D3 has a potency of approximately 5-10 times that of 1,25-dihydroxyvitamin D3 in the known in vivo vitamin D responsive systems. These systems include intestinal calcium transport, bone calcium mobilization, calcification of epiphyseal plate cartilage, and elevation of plasma calcium and phosphorus concentrations. Thus, 24,24-difluoro-1,25-dihydroxyvitamin D3 is the first known analogue with higher potency than 1,25-dihydroxyvitamin D3 in vivo.
Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs
Authors: Stevenson R. W. , Parsons J. A. , Alberti K. G.
Published: December 2017

The effects of peripheral and portal intravenous infusions of insulin on hepatic glucose production and glucose recycling have been compared in conscious diabetic dogs. Glucose turnover (Ra) was estimated using a priming dose of [3-3H]glucose and [1-14C]-glucose followed by constant intravenous infusion. Glucose recycling was calculated from 3H-Ra - 14C-Ra. In eight normal dogs, mean 3H-Ra was 3.0 mg X kg-1 X min-1 and recycling 19%. When these dogs were made diabetic with alloxan and streptozotocin the 3H-Ra rose to 6.2 mg X kg-1 X min-1 (P less than 0.001) and recycling to 24% (P less than 0.05). Insulin infusion for 2.5 h at 0.006 U X kg-1 X h-1 intraportally decreased 3H-Ra to 4.0 mg X kg-1 X min-1 (P less than 0.01 compared with untreated diabetic), whereas peripheral infusion at this rate had no significant effect. Insulin infusion at 0.05 U X kg-1 X h-1 by the peripheral and portal circulations reduced 3H-Ra to the normal range: 3.1 and 2.8 mg X kg-1 X min-1, respectively. Glucose recycling was also normalized by portal insulin infusion (20%) but was significantly decreased by peripheral infusion (11%, P less than 0.01). Thus the liver responds to lower infusion rates of insulin by the intraportal route, and only this mode of administration normalizes both hepatic glucose output and glucose recycling.
Energy cost of glucose storage in human subjects during glucose-insulin infusions
Authors: Thiebaud D. , Schutz Y. , Acheson K. , Jacot E. , DeFronzo R. A. , Felber J. P. , Jequier E.
Published: December 2017

The effect of graded levels of hyperinsulinemia on energy expenditure, while euglycemia was maintained by glucose infusion, was examined in 22 healthy young male volunteers by using the euglycemic insulin clamp technique in combination with indirect calorimetry. Insulin was infused at five rates to achieve steady-state hyperinsulinemic plateaus of 62 +/- 4, 103 +/- 5, 170 +/- 10, 423 +/- 16, and 1,132 +/- 47 microU/ml. Total body glucose uptake during each of the five insulin clamp studies was 0.41, 0.50, 0.66, 0.74, and 0.77 g/min, respectively. Glucose storage (calculated from the difference between total body glucose uptake minus total glucose oxidation) was 0.25, 0.29, 0.43, 0.49, and 0.52 g/min for each group, respectively, and represented over 60-70% of total glucose uptake. The net increment in energy expenditure after intravenous glucose was 0.08, 0.10, 0.14, 0.17, and 0.23 kcal/min, respectively. Throughout the physiological and supraphysiological range of insulinemia, there was a significant relationship (r = 0.95, P less than 0.001) between the increment in energy expenditure and glucose storage, indicating an energy cost of 0.45 kcal/g glucose stored. However, at each level of hyperinsulinemia, the theoretical value for the energy cost of glucose storage (assuming that all of the glucose is stored in the form of glycogen) could account for only 45-63% of the actual increase in energy expenditure that was measured by indirect calorimetry. These results indicate that factors in addition to glucose storage as glycogen must be responsible for the increase in energy expenditure that accompanies glucose infusion.
Cortisol and its possible role in regulation of sodium and potassium in human milk
Authors: Keenan B. S. , Buzek S. W. , Garza C.
Published: December 2017

Cortisol (F), Na, and K were measured in human milk samples taken every 4 h during 28 24-h cycles in 19 subjects. F in milk, measured by radioimmunoassay of unchromatographed extracts, demonstrated a circadian variation similar to that of plasma F and was dexamethasone-suppressible. Values ranged from 220 +/- 41 (SE) ng/dl at 2300 h to 1,214 +/- 210 at 0700 h. When milk extracts were chromatographed, a similar circadian variation was seen, and F ranged from 87 +/- 27 (SE) ng/dl at 2300 h to 784 +/- 164 at 700 h. The morning values of F exceeded previous estimates of corticosteroid binding capacity in milk, indicating the possibility of significant levels of unbound F. The subjects were divided into three groups according to time postpartum: I, 3.5-6 wk; II, 8-18 wk, and III, 20-32 wk. In milk, normalized values of F (unchromatographed) and electrolytes (x/means) were compared, with x the value at time t and means the mean value for a 24-h cycle. A significant circadian variation was seen in milk for (x/means)Na, (x/means)K, (x/means)Na/K, and x/means)F. Correlation of (x/means)F with (x/means)Na 4 h later was negative in all three groups (r = -0.36 to -0.56, P less than 0.10-0.001) as was (x/means)F vs. (x/means)Na/K (r = -0.33 to -0.61, P less than 0.10-0.001); (x/means)F vs. (x/means)K 4 h later was positive (r = 0.38 to 0.52, P less than 0.05-0.001). Dexamethasone administration caused a significant decrease in milk means Na and an increase in meansK in all five subjects (P less than 0.01). Thus, milk Na and K concentrations appeared regulated by adrenal corticosteroids.
Indexes of body cell mass: nitrogen versus potassium
Authors: Cohn S. H. , Vartsky D. , Yasumura S. , Vaswani A. N. , Ellis K. J.
Published: December 2017

In vivo neutron activation has provided investigators with a powerful tool for research on body composition. Total-body nitrogen (TBN), total-body potassium (TBK), and total-body water (TBW) were measured in 133 normal subjects. TBN, measured by neutron activation, is a measure of total-body protein, an index of body cell mass. TBK, also measured by a nuclear reaction, is an index of body cell mass as well as lean body mass. The mass and protein content of two compartments, muscle and nonmuscle lean tissue, were determined from the combined TBN-TBK data by compartmental analysis. In this study, nitrogen was separated into the actively metabolizing body cell mass component and the slowly metabolizing structural component. The TBK, which is 95% intracellular, was found to be more closely related to the actively metabolizing nitrogen than to TBN. The relationship of body cell mass, a concept originally proposed by Moore, to lean body mass, is shown through the relationship of TBN and TBK. The clinical significance of this study, is that TBK is the more sensitive and reliable indicator of changes in body cell mass. Maximum information on body composition, however, is obtained by the measurement of both TBK and TBN.
Effects of medium-chain triglyceride feeding on glucose homeostasis in the newborn rat
Authors: Pegorier J. P. , Leturque A. , Ferre P. , Turlan P. , Girard J.
Published: December 2017

The mechanism of the profound hypoglycemia that develops in newborn rats during a fast of 16-h beginning at birth has been investigated. This fasting hypoglycemia was completely reversed by giving oral medium-chain fatty acids (MCT). The rise in blood glucose induced by MCT feeding was not secondary to a decreased uptake of glucose by peripheral tissues because [6-3H]glucose turnover rate was increased in MCT-fed neonates. Several lines of evidence strongly suggest that MCT feeding was associated with a stimulation of hepatic gluconeogenesis. 1) The rate of [6-3H]glucose turnover was enhanced after MCT feeding. 2) A fivefold increase in the conversion of labeled lactate into glucose was observed in vivo after MCT feeding. 3) The rise in blood glucose induced by MCT feeding was totally suppressed by an inhibitor of gluconeogenesis (3-mercaptopicolinate). Despite their utilization for glucose synthesis, blood levels of lactate, alanine, and pyruvate were increased two- to threefold after MCT feeding. When MCT feeding was given in association with dichloroacetate, an activator of pyruvate dehydrogenase (PDH), no increase in blood lactate, alanine, and pyruvate was observed and the rise in glycemia was prevented. This suggested that hyperketonemia due to MCT feeding could decrease the oxidation of 3-carbon glucose precursors in peripheral tissues, secondary to an inhibition of PDH, and thus enhanced their release in blood. These data indicate that MCT feeding stimulates glucose production in the newborn rat, both by increasing the availability of gluconeogenic precursors and by a direct effect on hepatic gluconeogenesis.
Adrenergic regulation of avian pancreatic polypeptide secretion in vitro
Authors: Meglasson M. D. , Hazelwood R. L.
Published: December 2017

Adrenergic regulation of avian pancreatic polypeptide (APP) secretion from perifused microfragments of chicken pancreas was investigated with catecholamines and adrenoreceptor-specific analogues added to avian Krebs-Ringer perifusion medium containing 11.1 mM glucose. APP release was stimulated by the alpha-adrenoreceptor agonist phenylephrine (threshold 5 microM; maximum effective concn, 50 microM) and the beta-adrenoreceptor agonist isoproterenol (threshold 5 microM; maximum effective concn, 50 microM). Epinephrine (0.164 microM) and 50 microM norepinephrine also stimulated APP release. The results obtained suggest that APP secretion from chicken pancreas is regulated by dual, complementary alpha- and beta-adrenoreceptor mechanisms.
Vagotomy or atropine blocks hypoglycemic effect of insulin injected into ventromedial hypothalamic nucleus
Authors: Szabo A. J. , Iguchi A. , Burleson P. D. , Szabo O.
Published: December 2017

Stereotaxic microinjections of insulin (100 microU) into the ventromedial hypothalamic nucleus (VMN) resulted in rapid decrease, whereas injection of control saline into the same region caused a slight increase of hepatic venous plasma glucose concentration in rats. The hypoglycemic effect of insulin injected into the VMN was eliminated by pretreatment of the animals with atropine but not with propranolol or with phentolamine. Subdiaphragmatic vagotomy also prevented the decrease of hepatic venous plasma glucose concentration seen after microinjection of insulin into the VMN. These results support the hypothesis that the VMN is an insulin-sensitive glucoregulator center or that it is part of one and that the glucoregulatory impulse that originates in the VMN reaches the effector organ, the liver, through the cholinergic fibers of the vagus nerves.
Monoclonal antibody recognition of estrogen receptor in rabbit corpus luteum
Authors: Holt J. A. , Lorincz M. A. , King W. J.
Published: December 2017

We demonstrated previously by administering [3H]estradiol and using autoradiography that, in vivo, the exogenous estradiol that will sustain progesterone production is sequestered to nuclei of the luteal cells in corpora lutea of pseudopregnant rabbits. Our objective in the present experiments was to use an immunological method to demonstrate that estrogen receptor of the rabbit corpus luteum is associated with this uptake. For this purpose, we prepared nuclear extracts from corpora lutea removed from anesthetized pseudopregnant rabbits 10 min after arterial infusion of 125I-estradiol. These extracts were then analyzed by sucrose density gradient centrifugation in the presence and absence of monoclonal antibody against human breast cancer estrogen receptor. We found that the 125I-estradiol-binding component extracted with 0.5 M KCl from the nuclear pellet sediments in the 3-4S region in high-salt gradients; in the presence of monoclonal antibody (D-547 Sp2 gamma), the entire estradiol-binding component is shifted to the 8-9S region, indicating the formation of immunocomplex with the 125I-estradiol-receptor moiety. The principal estradiol-binding component that can be observed in the 3-4S region of high-salt gradients of cytosol of rabbit corpora lutea reacts with this antibody regardless of whether 125I- or [3H]estradiol is given in vivo or in vitro. In both cytosol and nuclear extracts of luteal tissue, unlabeled diethylstibestrol totally inhibits the binding of radiolabeled estrogen to this antibody-shifted 125I- or [3H]estradiol-binding moiety; neither progesterone nor testosterone inhibit binding of radiolabeled estrogen to the antibody-shifted moiety. From these findings we conclude that sequestering of estradiol by the rabbit corpus luteum in vivo is accomplished by the steroid-specific estrogen receptor that shares characteristics of the estrogen receptor found in human breast cancers, including a) antigenic features and b) the capacity to translocate estrogens from the cytosol to the nuclear fraction.
Pertussis toxin uncouples dopamine agonist inhibition of prolactin release
Authors: Cronin M. J. , Myers G. A. , MacLeod R. M. , Hewlett E. L.
Published: December 2017

Pertussis toxin, a protein exotoxin produced by Bordetella pertussis, markedly reduced or eliminated the ability of dopamine or the dopamine agonist bromocriptine to inhibit prolactin release from anterior pituitary cells in vitro. Toxin-mediated reversal of the effect on dopamine agonist inhibition of prolactin release occurred with a lag of greater than 6 h, was maximal by 24 h, and persisted for at least 6 days after removal of the toxin from the medium. The toxin reduced dopamine agonist efficacy without altering potency or directly modifying the dopamine receptor (as measured by [3H]spiperone binding). The ability of dopamine to reduce cellular cyclic AMP content was also antagonized by pertussis toxin, supporting the hypothesis that reduction of cellular cyclic AMP content and inhibition of prolactin secretion may be causally related. These data demonstrated that pertussis toxin can prevent the typical inhibitory action of dopamine agonists on anterior pituitary prolactin release and suggest that this receptor-mediated inhibitory hormone system is analogous to other inhibitory receptors coupled to adenylate cyclase.
Effect of endurance training on glucose kinetics during exercise
Authors: Brooks G. A. , Donovan C. M.
Published: December 2017

Control and endurance-trained rats received continuous infusions via jugular catheters of [U-14C]- and [6-3H]glucose under one of three conditions: rest (Re), running at 13.4 m/min (easy exercise, EE), or running at 26.8 m/min (hard exercise, HE). Arterial blood was sampled from carotid catheters. Blood glucose levels were not different between groups at rest (3.88 +/- 0.19 mM) or EE (4.32 +/- 0.35 mM). During HE, trained animals maintained blood glucose better (3.41 +/- 0.34 mM) than did untrained animals (3.03 +/- 0.42 mM). Respiratory exchange ratio (R) increased from rest (0.79 +/- 0.05) to exercise and was significantly lower in trained than in untrained animals during HE (0.87 +/- 0.02 vs. 0.93 +/- 0.03). Glucose turnover (Rt) calculated from [3H]glucose was not different between groups at rest (46.2 +/- 2.7 mumol x kg-1 x min-1). Turnover increased during EE to 91.5 +/- 7.5 vs. 72 +/- 8.5 mumol x kg-1 x min-1 in untrained and trained animals, respectively. During HE, Rt rose to 95.0 +/- 12.6 in trained animals but fell to 78.7 +/- 9.9 mumol x kg-1 x min-1 in untrained animals. The percentage of glucose flux oxidized increased from rest (44.0 +/- 6.8%) to exercise and was significantly lower in trained (73.7 +/- 4.3%) than in untrained animals (95.1 +/- 3.8%) during HE. Metabolic clearance rate increased from 12.5 +/- 0.8 in Re to 29.4 +/- 6.0 ml x min-1 x kg-1 in HE but did not differ between groups. Training improved glucose homeostasis during HE by increasing the glucose flux and by reducing the fraction of the flux lost to oxidation.
Carotid vascular control of ACTH secretion in lambs
Authors: Wood C. E. , Rudolph A. M.
Published: December 2017

To test the hypothesis that changes in carotid vascular pressure influence ovine ACTH and corticosteroid secretion, we subjected 6- to 7-wk-old conscious lambs to bilateral carotid occlusion with or without prior vagosympathetic blockade. Reversible vagosympathetic blockade, produced by injection of 2% lidocaine onto the vagosympathetic trunks, inhibited the reflex changes in heart rate after intravenous injection of phenylephrine or during carotid occlusion. Vagosympathetic blockade by itself did not alter arterial pressure or heart rate but did increase circulating levels of ACTH and corticosteroids. This suggests that afferent fibers in the vagosympathetic trunks tonically inhibit the secretion of ACTH. Bilateral carotid occlusion did not change plasma ACTH or corticosteroid concentrations. Bilateral carotid occlusion plus prior vagosympathetic blockade stimulated increases in plasma ACTH and corticosteroid concentrations that were larger than responses to vagosympathetic blockade alone. The results demonstrate that changes in carotid vascular pressure influence ovine ACTH and corticosteroid secretion only during vagosympathetic blockade and therefore suggest that carotid vascular mechanoreceptors interact with other mechanoreceptors having vagosympathetic afferent fibers.