bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered insulin and glucagon secretion in perfused ethionine-treated rat pancreases
Authors: Axen K. V. , Pi-Sunyer F. X.
Published: December 2017

The endocrine secretory function of rat pancreases in which pancreatitis had been induced by feeding rats a 0.5% ethionine diet was investigated. Despite loss of 50% of exocrine tissue and widespread destruction of acinar structure, pancreatic insulin and glucagon contents and 4-h fasting plasma insulin levels in vivo did not differ significantly from those of food-restricted, weight-matched controls. Plasma glucose concentrations (fasting and after oral glucose) were significantly lower than control. In isolated, perfused ethionine-treated pancreases secretin failed to stimulate insulin secretion, whereas basal insulin secretion and insulin responses to glucose, arginine, gastric inhibitory polypeptide, vasoactive intestinal peptide (VIP), and somatostatin were similar to those of controls. Basal glucagon secretion was elevated in ethionine-treated pancreases, and glucagon outputs in response to arginine, VIP, and somatostatin showed a consistent trend toward higher levels than those of controls. These findings demonstrate that ethionine-induced pancreatitis selectively impairs islet secretory function. These effects may be due to damage to islet cell membranes by exocrine enzymes and/or a direct pathogenic action of ethionine on the islets.
Endurance training affects lactate clearance, not lactate production
Authors: Donovan C. M. , Brooks G. A.
Published: December 2017

Primed-continuous infusion of [2-3H]- and [U-14C]lactate was used to study the effects of endurance training (running 2 h/day at 29.4 m/min up a 15% gradient) on lactate metabolism in rats. Measurements were made under three metabolic conditions: rest (Re), easy exercise (EE, 13.4 m/min, 1% gradient) and hard exercise (HE, 26.8 m/min, 1% gradient). Blood lactate levels in trained animals increased from 1.0 +/- 0.09 mM in Re to 1.64 +/- 0.21 in EE and 2.66 +/- 0.38 in HE. Control animals also demonstrated an increase in blood lactate with increasing work rate, but values were 1.93 +/- 0.21 and 4.62 +/- 0.57 mM at EE and HE, respectively. Lactate turnover rates (RtLA) measured with [U-14C]lactate increased from 214.0 +/- 17.0 mumol.kg-1.min-1 in Re to 390.3 +/- 31.6 in EE and 518.1 +/- 56.4 in HE. No significant differences in RtLA were observed between controls and trained animals under any condition. Identical relationships between RtLA and exercise or training were obtained with [2-3H]lactate; however, the values obtained were consistently 90% higher than those observed with [U-14C]lactate. Metabolic clearance rate (MCR) for 14C was not significantly different in Re between controls and trained animals (180.6 +/- 27.7 ml.kg-1.min-1). Metabolic clearance of lactate in trained animals was 37 and 107% greater than in controls during EE and HE, respectively. Results indicate that the effect of endurance training is not on production of lactate but on its clearance from the blood.
Glucose uptake and insulin sensitivity in rat muscle: changes during 3-96 weeks of age
Authors: Goodman M. N. , Dluz S. M. , McElaney M. A. , Belur E. , Ruderman N. B.
Published: December 2017

It has been demonstrated that aging diminishes the rate of glucose utilization by rat skeletal muscle. To determine the basis for this occurrence as well as its temporal sequence, glucose utilization was examined in isolated hindquarters of 3-, 5-, 8-, 16-, 24-, 48-, and 96-wk-old male Sprague-Dawley rats. Glucose utilization diminished progressively during early development (3-5 wk) and adolescence (5-16 wk) in hindquarters perfused in the absence of added insulin. At the same time there was a progressive shift of the insulin dose-response curve to the right, indicating diminished insulin sensitivity and a marked decrease in maximum insulin responsiveness. In contrast, between 24 and 96 wk of age, insulin sensitivity and the rate of glucose utilization in the absence of added insulin did not decrease, and there was only a small decrease in maximum responsiveness. The rate-limiting step in glucose utilization under all conditions was glucose transport. Even at high insulin concentrations, free glucose was not detected in the muscle cells of young or old rats, the uptake of 2-deoxyglucose diminished in parallel with that of glucose, and there was no evidence of a defect in glucose metabolism. These findings indicate that in the Sprague-Dawley rat glucose transport into skeletal muscle and in particular its sensitivity and responsiveness to insulin diminish progressively during early development and adolescence. No further marked changes occurred up to at least 96 wk of age. To what extent these early age-associated changes are due to insulin binding and to what extent to alterations in the glucose transport system per se remains to be determined.
Brown adipose tissue in genetically obese (fa/fa) rats: response to cold and diet
Authors: Triandafillou J. , Himms-Hagen J.
Published: December 2017

Young genetically obese (fatty, fa/fa) rats (7-8 wk old) maintained on a chow diet at 28 degrees C have a relatively normal amount of brown adipose tissue (BAT) (normal protein content, normal noradrenaline content, normal or slightly reduced cytochrome oxidase content, 30% reduction in DNA content) with cells grossly hypertrophied by accumulation of lipid. The binding of purine nucleotides by BAT mitochondria is lower in fa/fa rats than in lean rats, suggesting a lesser thermogenic activation of this tissue. Acute exposure to cold (24 h at 4 degrees C) activates BAT thermogenesis (visible hyperemia, marked increase in mitochondrial binding of purine nucleotides, depletion of noradrenaline content) in fa/fa rats as in lean rats. In contrast, feeding a cafeteria diet to young fa/fa rats fails to activate BAT (no increase in mitochondrial binding of purine nucleotides) as it does in lean rats, and these rats accumulate more extra fat (increase in weight of gonadal white adipose tissue) than do cafeteria diet-fed lean rats. It is concluded that the young fa/fa rat has normal cold-induced nonshivering thermogenesis in BAT but defective diet-induced thermogenesis in BAT and that the consequent reduction in energy expenditure, coupled with hyperphagia, contributes to the development of its obesity. The most probable location for the defect is suggested to be associated with the hypothalamus.
Cerebral metabolism of amino acids and glucose in fed and fasted sheep
Authors: Pell J. M. , Bergman E. N.
Published: December 2017

Net cerebral uptake from or release into whole blood of oxygen, carbon dioxide, glucose, amino acids, lactate, pyruvate, ketone bodies, and acetate was estimated in fed, 3-day-fasted, and 6-day-fasted sheep. The respiratory quotient was similar in all three groups of sheep (approximately 0.95). Glucose uptake (35 mumol X min-1 X 100 g-1) was maintained during fasting, and about 94% of the cerebral oxygen consumption could have been accounted for by glucose oxidation in all sheep. A cerebral uptake of the branched-chain amino acids (leucine, isoleucine, and valine) and proline also was observed with a concomitant production of glutamine and asparagine. The brains of fed and 3-day-fasted sheep were in nitrogen balance, but a small net release of nitrogen occurred in 6-day-fasted sheep (2 mumol N. min-1 X 100 g-1). A small amount of pyruvate was always released (1.4 mumol X min-1 X 100 g-1) into the blood, whereas lactate was released (6 mumol X min-1 X 100 g-1) only in 6-day-fasted sheep. Ketone body and acetate utilization always was negligible when compared with that for glucose. The total cerebral nonglucose carbon release found for 6-day-fasted sheep was equivalent to 23% of the glucose carbon taken up, although only 8% could have been derived directly from glucose. Thus, metabolism by the ovine brain seems resistant to prolonged periods of hypoglycemia with only small adaptations occurring after a 6-day fast.
Optimal segments: a method for smoothing tracer data to calculate metabolic fluxes
Authors: Finegood D. T. , Bergman R. N.
Published: December 2017

Metabolic fluxes (Ra and Rd) are calculated in the nonsteady state using Steele's equations. These calculations require estimates of the values and rates of change of glucose and specific activity at discrete sampling times. Data smoothing minimizes the effect of measurement error that confounds the Ra and Rd calculations. We compared three smoothing methods: a) moving average, b) polynomial fitting, and c) optimal segments, a new technique that utilizes optimization methods. Experimental designs were simulated: 1) constant infusion of glucagon in depancreatized dogs, and 2) glucose oscillations generated by constant high-level glucose infusion. Measurement error was added to raw data. After smoothing, fluxes were calculated and compared to the "actual" Ra and Rd. Ra calculated from unsmoothed noisy data were in error by an average 39%. Error was reduced by smoothing to: 23%, moving average; 18%, polynomial fitting; 15%, optimal segments. Optimal segments was best for calculating Ra (P less than 0.01) and was better than or equal to other methods for Rd. Distortion in flux patterns was greatest for polynomial fitting (P less than 0.01) and least for optimal segments (P less than 0.001). Optimal segments is the method of choice for smoothing tracer data; it improves calculations of Ra and Rd with minimal distortion.
Reciprocal changes in gluconeogenic enzyme activity in liver and kidney by VMH lesion
Authors: Nagai K. , Inoue S. , Nakagawa H.
Published: December 2017

The effects of bilateral lesions of the ventromedial hypothalamus (VMH) on daily rhythms of the activity of a gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), in the liver and kidney of rats were examined. PEPCK activity in the liver was considerably lowered by VMH lesions, but its rhythm remained similar to that of control liver. In contrast, PEPCK activity in the kidney was markedly elevated by the lesions. From these findings, it is suggested that the VMH is not the site of the master biological clock of the rhythm of PEPCK activity. Although these results do not exclude the possibility that hyperphagia and hyperinsulinemia associated with VMH lesions induce changes in the levels of PEPCK activities, they support the hypothesis that suppression of the sympathetic nervous system causes the changes in PEPCK activity through direct or indirect mechanisms. These findings also suggest that the reciprocal change in PEPCK activities in the liver and kidney after VMH lesions is related to complementary functions of the two organs in maintenance of homeostasis of blood glucose.
Evidence of a defect in energy expenditure in 7-day-old Zucker rat (fa/fa)
Authors: Planche E. , Joliff M. , de Gasquet P. , Leliepvre X.
Published: December 2017

The aim of the investigation was to see whether a defect in energy expenditure could be found in the Zucker rat at the onset of obesity. Obese (fa/fa) and lean (Fa/fa) 7-day-old pups were studied at three ambient temperatures. At 33 degrees C fa/fa pups showed a reduction in oxygen consumption, respiratory CO2 production, in vivo oxidation of injected [1-14C]palmitic acid, as well as in core temperature. When the pups were kept at 28 degrees C, the difference between genotypes was considerably accentuated, thus indicating a subnormal thermogenic response of the fa/fa pups to a mildly cold environment. At 20 degrees C, however, the metabolic rates dropped to the same low level, and the core temperature equilibrated with ambient temperature in both genotypes. The results demonstrate that the 1-wk-old fa/fa pup has a defect in thermoregulatory thermogenesis. The magnitude of the deficit in energy expenditure was more than adequate to account for the 50% greater fat content of 7-day-old fa/fa pups.
Cellular basis of insulin resistance in chronic uremia
Authors: Maloff B. L. , McCaleb M. L. , Lockwood D. H.
Published: December 2017

To define the cellular alterations responsible for insulin resistance during uremia, we studied insulin action in adipocytes isolated from rats 2 wk after 75% partial nephrectomy. Insulin binding to fat cells and purified liver plasma membranes prepared from uremic rats was unaltered. In contrast, hexose transport was significantly decreased, with and without insulin, in the fat cells from the uremic animals. The concentration of insulin that elicited half-maximal response was not altered. Glucose utilization was reduced in the absence or presence of insulin by partial nephrectomy. The stimulation of hexose transport and glucose metabolism by the insulin mimickers, hydrogen peroxide and vitamin K5, were also inhibited. Hexose transport activity in adipocytes obtained from uremic rats was no longer decreased when pieces of fat tissue were cultured for 20 h. Finally, hexose transport was reduced in the cells isolated from normal adipose tissue that was preincubated for 3 h with uremic serum, but insulin binding was not different than control. Thus, insulin resistance associated with uremia may be primarily accounted for by altered postreceptor events that appear to result from a circulating factor(s).
Hypothalamic hyperinsulinemia and obesity: role of adrenal glucocorticoids
Authors: King B. M. , Banta A. R. , Tharel G. N. , Bruce B. K. , Frohman L. A.
Published: December 2017

The effects of adrenalectomy on the obesity and hyperinsulinemia induced by ventromedial hypothalamic (VMH) lesions were studied in female rats. Plasma insulin and glucose levels were assayed after a 4-h fast and 17 min after the initiation of a meal (6 ml sweetened milk in 7 min). The development of hypothalamic obesity was prevented by prior adrenalectomy and restored by administration of corticosterone. Adrenalectomy abolished both the basal and postabsorptive hyperinsulinemia observed in sham-adrenalectomized rats with VMH lesions. Corticosterone treatment of adrenalectomized animals enhanced both basal and postabsorptive insulin levels, but adrenalectomized rats with VMH lesions were hyperinsulinemic compared with animals with sham lesions only under the postabsorptive condition. Postabsorptive glucose levels were unaffected by either the lesion or adrenal ablation. The results support our previous conclusion that postabsorptive hyperinsulinemia is of greater importance than is basal hyperinsulinemia in the pathogenesis of hypothalamic obesity. Although the results are consistent with a stimulatory role of corticosterone on food intake mediating the postabsorptive hyperinsulinemia, a primary effect on CNS loci involved with the regulation of insulin secretion is also possible.
Characterization of alpha-keto acid transport across blood-brain barrier in rats
Authors: Conn A. R. , Fell D. I. , Steele R. D.
Published: December 2017

The transport of keto acids, monocarboxylic acids, and ketone bodies was studied in barbiturate-anesthetized, adult male Sprague-Dawley rats. [1-14C]propionate and D-3-[3-14C]hydroxybutyrate were found to cross the blood-brain barrier with brain uptake indexes of 43.53 and 7.10%, respectively. Transport of both of these substrates was saturable, with the values of transport Km being 2.03 and 6.54 mM, respectively. A Ki of 0.68 mM was derived from competition data measuring the uptake of [1-14C]alpha-ketoisocaproate in the presence of unlabeled alpha-ketobutyrate. This finding and results from classical inhibition studies support competition for transport of keto acids for a common carrier. The brain uptake of [1-14C]propionate was significantly reduced by keto acids and ketone bodies and the transport of D-3-[3-14C]hydroxybutyrate was significantly inhibited by unlabeled monocarboxylic acids, keto acids, and acetoacetate. Evidence for competitive transport of alpha-keto acids, monocarboxylic acids, and ketone bodies is presented in the form of classical double-reciprocal inhibition plots and of labeled monocarboxylic acids and ketone bodies by an increasing concentration of unlabeled alpha-ketoisocaproate, the latter method yielding Ki values of 0.29 and 0.63 mM, respectively. The brain uptake of labeled propionate was inhibited by unlabeled D-3-hydroxybutyrate. A Ki of 6.43 mM, derived from this data, approximated the Km of transport of D-3-hydroxybutyrate, suggesting that ketone bodies and monocarboxylic acids compete for transport via the same carrier that is operative for keto acids.
Hormones modulate adipocyte membrane potential ATP and lipolysis via free fatty acids
Authors: Vallano M. L. , Lee M. Y. , Sonenberg M.
Published: December 2017

The hypothesis that lipolytic hormones reduce the mitochondrial electrical potential in rat white adipocytes via free fatty acids (FFA) was examined. Hormonal effects on plasma and mitochondrial membrane potentials were evaluated with [3H]triphenylmethylphosphonium (TPMP+) and 86Rb+. FFA generation was controlled by varying medium albumin concentrations. In 4.0% albumin buffer, adrenocorticotropin or l-epinephrine increased intracellular FFAs, produced cellular TPMP+ efflux, ATP depletion, release of FFAs and glycerol, and no change in 86Rb+ distribution. In 0.5% albumin buffer, greater intracellular FFA accumulation accompanied greater TPMP+ and ATP depletion, significant loss of cell-associated 86Rb+, and a concomitant inhibition of FFA and glycerol release. Exogenous addition of FFAs mimicked the effect of hormones on adipocyte TPMP+ distribution. TPMP+ and 86Rb+ uptake into adipocyte "ghosts" were unaffected by hormones. We suggest that mitochondrial membrane depolarization is a metabolic response to hormones via FFA accumulation by white adipocytes. The additional hormonal effects that were observed in 0.5% albumin buffer may be related to inhibition of lipolysis secondary to intracellular ATP depletion.
Evidence for a longitudinal pathway in rat hypothalamus that controls FFA mobilization
Authors: Coimbra C. C. , Migliorini R. H.
Published: December 2017

In initial exploratory experiments, bilateral, symmetrical, relatively large electrolytic lesions were produced, injuring anterior, middle, and posterior hypothalamus but respecting the midlateral region. Only lesions in the preoptic-anterior hypothalamic region and in the posterior hypothalamus were effective in blocking free fatty acid (FFA) mobilization induced by intravenous 2-deoxyglucose. Lesions in the ventromedial hypothalamus were ineffective. In subsequent experiments, suppression of plasma FFA response to the drug was observed in rats with small, globular (0.5-1.0 mm diam), bilateral lesions either in the preoptic (PO) or in the lateral hypothalamic (LH) areas. Groups of animals were then prepared in which a unilateral lesion in the PO area was combined with a contralateral lesion in the LH area. Plasma FFA response to 2-deoxyglucose in these rats was also blocked but not in rats having only unilateral lesions. The hyperglycemic response to 2-deoxyglucose was not affected in any of the experimental groups. These data suggest that a longitudinal pathway connecting PO, LH, and posterior hypothalamic areas is involved in FFA mobilization from adipose tissue in rats.
Effects of verapamil on renin and aldosterone in the dog and rat
Authors: Roy M. W. , Guthrie G. P. , Holladay F. P. , Kotchen T. A.
Published: December 2017

The purpose of this study was to evaluate the effects of calcium channel blockade on renin secretion and plasma aldosterone. Verapamil infusion (0.004 mg X kg-1 X min-1) into the renal artery of uninephrectomized dogs with an intact kidney resulted in significant increases (P less than 0.05) in renal blood flow, creatinine clearance, and the excreted fractions of Na+ and Cl-; renin secretion decreased (P less than 0.05) and plasma aldosterone did not change. Conversely, renal arterial infusion of verapamil in dogs with nonfiltering, denervated, papaverine-treated kidneys resulted in no change in renal blood flow and a significant increase (P less than 0.05) in renin secretion. In the rat, compared with untreated control animals, dietary verapamil (12.5 mg X kg-1 X day-1) did not effect plasma renin activity but significantly suppressed plasma aldosterone (P less than 0.001) in animals on NaCl-restricted [14.7 +/- 5.4 vs. 41.6 +/- 7.8 ng/dl (SE)] and NaCl-free [103.7 +/- 7.5 vs. 156.7 +/- 18.7 ng/dl (SE)] diets. In addition, verapamil suppressed (P less than 0.0003) plasma corticosterone [16.1 +/- 5.4 vs. 52.8 +/- 7.1 microgram/dl (SE)]. Thus, acute but not chronic verapamil administration stimulates renin release in the nonfiltering kidney, and chronic verapamil inhibits adrenal mineralocorticoid and glucocorticoid secretion. The disparate effects of verapamil on renin secretion from intact and nonfiltering kidneys may be due to actions of the Ca2+ channel blocker on renal hemodynamic and/or renal tubular mechanisms in the intact kidney that mask a direct effect of verapamil on renin-secreting cells.
A potassium-induced mitochondrial protein related to aldosterone biosynthesis
Authors: Meuli C. , Muller J.
Published: December 2017

Late steps of aldosterone biosynthesis, i.e., the conversions of corticosterone to 18-hydroxycorticosterone and aldosterone, are catalyzed by a mitochondrial cytochrome P-450. Resumption of potassium intake by potassium-depleted rats resulted within 2 days in a marked stimulation of these conversions, as reflected by increased production of aldosterone and 18-hydroxycorticosterone and decreased outputs of deoxycorticosterone, corticosterone, and 18-hydroxy-11-deoxycorticosterone by incubated capsular portions of the adrenal glands. The stimulation of aldosterone biosynthesis was accompanied by the appearance of a protein with a molecular weight of about 49,000 in the mitochondria of the zona glomerulosa but not of the inner zones of the adrenal cortex. Over 48 h of potassium repletion, the amount of this protein increased in parallel with the activity of the final steps of aldosterone biosynthesis. According to its molecular weight, its zone specificity, and the time course of its appearance, this protein might represent the steroid 18-methyl oxidase (cytochrome P-450CMO for corticosterone methyl oxidase) that catalyzes the conversion of corticosterone to 18-hydroxycorticosterone and aldosterone.
Vitamin D-deficient rats produce reduced quantities of a nutritionally adequate milk
Authors: Brommage R. , DeLuca H. F.
Published: December 2017

Pups raised by lactating rats deficient in vitamin D do not grow normally, and we have shown previously that this growth failure results from a maternal rather than a neonatal defect. This result indicates that vitamin D-deficient rats produce reduced amounts of milk and/or the milk they do produce is nutritionally incomplete. To examine the first of these possibilities, 3H2O and 42K in separate experiments were given to lactating rats at 13 days postpartum, and the amount of isotope transferred to their pups during the next 24 h was determined. The amount of milk produced during this period was calculated from the measured concentrations of 3H2O and 42K in milk. The specific activity of 3H2O in maternal plasma was kept constant by providing 3H2O in the drinking water of the dams. Vitamin D-deficient rats were found to produce only 19.5 +/- 1.8% determined by the 3H2O method and 23.2 +/- 1.1% by the 42K method (means +/- SD) of the amount of milk produced by vitamin D-replete rats. The composition of milk from vitamin D-deficient rats was examined to determine its nutritional value. Vitamin D-deficient milk contains elevated levels of fat, and the skim fraction contains more protein, potassium, calcium, and inorganic phosphorus but less carbohydrate than normal milk. When vitamin D-deficient dams were given two pups to nurse rather than the eight usually provided, pup growth was equivalent to that of vitamin D-replete pups. Furthermore, femur dry weights and degree of mineralization were similar in vitamin D-deficient and -replete pups of equivalent body weight.(ABSTRACT TRUNCATED AT 250 WORDS)
In vitro evidence of a role for inhibin in female rabbits
Authors: Goodman A. L.
Published: December 2017

To examine a regulatory role for inhibin in female rabbits, an in vitro bioassay for inhibin activity was modified to use cultured rabbit pituitary cells and charcoal-extracted porcine follicular fluid (pFFx) as a reference preparation. pFFx inhibited follicle-stimulating hormone (FSH) release in a dose-dependent manner in cultures from both intact (I) and castrate (C) does at doses that also inhibited FSH release by cultured rat pituitary cells. Basal FSH release by I cells was inhibited greater than 10% by 0.02% (vol/vol) and greater than 90% by greater than or equal to 0.2% pFFx, whereas in C cells maximal inhibition of FSH release plateaued at only approximately 75%. FSH secretion was restored after removal of pFFx in day 2 media. Luteinizing hormone (LH) release by C cells was not inhibited at any dose of pFFx, but in I cells LH was progressively inhibited to approximately 60% of control levels during day 2 (but not day 1). Charcoal-extracted media (0.25-1%) in which 5 X 10(5) rabbit granulosa cells had been earlier cultured for 72 h produced a parallel inhibition of FSH release. The present findings demonstrate that 1) rabbit pituitary cells are responsive to inhibin, i.e., pFFx preferentially inhibited FSH secretion in a direct, graded, and reversible manner and 2) rabbit follicular granulosa cells secrete an inhibin-like substance.
Protein synthesis versus energy state in contracting muscles of perfused rat hindlimb
Authors: Bylund-Fellenius A. C. , Ojamaa K. M. , Flaim K. E. , Li J. B. , Wassner S. J. , Jefferson L. S.
Published: December 2017

The goal of these studies was to evaluate acute changes in protein metabolism in skeletal muscle in response to contractile activity. Rates of protein synthesis were measured by following L-[U-14C]phenylalanine incorporation into protein in muscles of the perfused rat hindlimb at rest, during 10 min of maximal isometric muscle contractions, and during 10 min of recovery. Synthesis measurements were carried out under conditions that ensured that the specific radioactivity of the tRNA-bound precursor amino acid was equal to that of extracellular phenylalanine. Protein degradation was estimated by measuring the release of Nt-methylhistidine. Rates of synthesis were markedly inhibited in response to muscle contractions in tibialis anterior, gastrocnemius, and plantaris but were unaffected in soleus. Rates of synthesis returned toward those observed in the resting condition during the recovery period. Rates of degradation were also markedly inhibited in response to muscle contractions. Decreased rates of synthesis correlated with reduced tissue contents of ATP and creatine phosphate, a reduced ATP/ADP, and an elevated tissue content of lactate. The results demonstrate that isometric contractions in muscles consisting of a high proportion of fast glycolytic fibers result in a marked depression in rates of protein synthesis that may be due to an altered energy state.
Aldosterone blocks adrenal compensatory hypertrophy in the rat
Authors: Grizzle W. E. , Dunlap N. E.
Published: December 2017

We report that adrenal compensatory hypertrophy occurs in intact and hypophysectomized anesthetized rats as well as in rats in which endogenous ACTH is suppressed by administration of dexamethasone or of dexamethasone plus low-dose ACTH. However, adrenal compensatory hypertrophy is blocked in intact and hypophysectomized animals when aldosterone alone or the combination of aldosterone, dexamethasone, and ACTH is administered using Alzet pumps. These data support previous reports that questioned the validity of the hypothesis that adrenal compensatory hypertrophy is controlled by the glucocorticoid-ACTH negative feedback system. These results require modification of current hypotheses concerning the mechanism of adrenal compensatory hypertrophy to allow for a central nervous system or other effect of aldosterone.
Catecholamine physiology in ovine fetus. II. Metabolic clearance rate of epinephrine
Authors: Palmer S. M. , Oakes G. K. , Lam R. W. , Hobel C. J. , Fisher D. A.
Published: December 2017

This study measured the metabolic clearance rate (MCR) of epinephrine (E) in 13 chronically catheterized fetal lambs between 120 and 145 days gestation. The E-MCR was determined by a constant infusion method at an E infusion rate of 0.1 microgram/kg estimated fetal wt. Fetal and maternal arterial blood samples were taken for measurements of catecholamine levels, pH, blood gases, and glucose. There was a significant positive correlation between gestational age and E-MCR (r = 0.87, P less than 0.001). The E production rate in fetuses less than 132 days (n = 6) (1,234 +/- 301 pg/min) was not significantly different from fetuses greater than or equal to 132 days (n = 7) (1,195 +/- 242). Catecholamine infusion resulted in a decrease in pH from a control value of 7.37 +/- 0.01 to 7.31 +/- 0.01 by 15 min of infusion, but there were no significant changes in fetal heart rate or blood pressure. The mean fetal plasma glucose concentration increased 45% above base line at 15 and 20 min and 65% above base line by 30 min of catecholamine infusion. After 60 min of infusion plasma norepinephrine (NE) increased from 380 +/- 60 to 520 +/- 75 pg/ml and plasma dopamine from 100 +/- 20 to 240 +/- 50 pg/ml (both P less than 0.05). These results indicate that E-MCR increases with maturation in the absence of a change in basal E production.
Vitamin D is not directly necessary for bone growth and mineralization
Authors: Underwood J. L. , DeLuca H. F.
Published: December 2017

To determine whether vitamin D has a direct action on bone growth and mineralization, severely vitamin D-deficient rats were infused continuously for 10 days with calcium and phosphorus solutions intrajugularly to maintain plasma calcium and phosphorus levels equal to those in rats on the same diet given vitamin D. Rats from the same litters identically treated were given 75 IU of vitamin D3 every 3 days and infused with saline for the 10-day period for comparison. Infusion of calcium and phosphorus to the vitamin D-deficient rats induces bone growth and mineralization equal to that of the rats given vitamin D as revealed by femur length, femur weight, total femur ash, percent femur ash, and epiphyseal plate width. The mineral deposited had a calcium-to-phosphorus ratio of 1.6 identical to the mineral deposited in the rats given vitamin D and unlike controls maintained in the vitamin D-deficient state without infusions. The vitamin D-deficient rats infused with calcium and phosphorus had greater amounts of mineral and matrix in their femurs than did those treated with vitamin D. This result demonstrates that some form of vitamin D does have a direct effect on bone. The most likely possibility is that bone resorption in relation to modeling or calcium mobilization for calcium homeostasis or both are compromised in extreme vitamin D deficiency. The above results strongly support the concept that vitamin D is not necessary for and does not stimulate directly bone growth and mineralization. Vitamin D therefore supports bone growth and mineralization indirectly by elevating plasma calcium and phosphorus levels.
Muscle protein synthesis: regulation of a translational inhibitor
Authors: Buse M. G. , Cheema I. R. , Owens M. , Ledford B. E. , Galbraith R. A.
Published: December 2017

Insulin and branched-chain amino acids are known to stimulate protein synthesis in skeletal muscle. Extracts prepared from rat diaphragms after incubation in balanced salt solution and glucose alone yielded heat- and acid-stable, TCA-precipitable, nondialyzable factor(s) that inhibit protein synthesis when added to rabbit reticulocyte lysates. Polyribosomal profiles of inhibited lysates were consistent with a defect in peptide-chain initiation. Addition of insulin and amino acids to the diaphragm incubation media partially removed the inhibition seen with the muscle extract and was accompanied by an increase in polysomes and decreased subunits. Similarly, extracts prepared from rat hindlimb muscle 48 h after induction of diabetes were much more inhibitory in rabbit reticulocyte lysates than extracts from control rats. Polyribosomal profiles were consistent with defective peptide-chain initiation. Trypsin treatment before assay abolished the inhibitory activity of muscle extracts from diabetic rats. Because translation-inhibiting peptide(s) appear to be under metabolic and/or hormonal control, their possible role in muscle protein homeostasis warrants further study.
Glucose counterregulation during prolonged hypoglycemia in normal humans
Authors: Bolli G. B. , Gottesman I. S. , Cryer P. E. , Gerich J. E.
Published: December 2017

To study glucose counterregulation under conditions approximating those of clinical disorders in which hypoglycemia develops gradually and is reversed over a prolonged period, we injected regular insulin subcutaneously, in a dose (0.15 U/kg) selected to produce two- to threefold increases in plasma insulin, in 11 normal human volunteers and measured plasma glucose, insulin, C-peptide, and counterregulatory hormone concentrations as well as rates of glucose production, glucose utilization, and insulin secretion over 12 h. The data suggest that the mechanisms of gradual recovery from prolonged hypoglycemia may differ from those of rapid recovery from short-term hypoglycemia produced by intravenous injection of insulin in that 1) both stimulation of glucose production and limitation of glucose utilization contribute to recovery from prolonged hypoglycemia; 2) increases in glucagon, epinephrine, growth hormone, and cortisol secretion as well as a decrease in insulin secretion may all participate in glucose counterregulation during prolonged hypoglycemia; 3) epinephrine may play a more important role than glucagon during prolonged hypoglycemia. The latter two conclusions are based primarily on the temporal relationships between changes in the rates of glucose turnover and changes in plasma hormone concentrations and should not be considered proved. However, they provide the basis for testable hypotheses concerning the physiology of gradual recovery from prolonged hypoglycemia that can be expected to be relevant to the pathophysiology of clinical hypoglycemia.
Uterus of the rat contains prolactin inhibitory activity
Authors: Gorospe W. C. , Freeman M. E.
Published: December 2017

Activity found in crude acid extracts of uterine tissue obtained from pseudopregnant, proestrous, or ovariectomized rats causes a dose-dependent inhibition of prolactin (PRL) release with a concurrent intracellular accumulation of PRL by anterior pituitary cells in culture. The absence of any significant effects imposed by the uterine extracts on basal luteinizing hormone or follicle-stimulating hormone secretion in these same cultures suggests that the activity is a noncytotoxic inhibitor of PRL secretion. Furthermore, failure of uterine extracts to degrade standard rat PRL after a 24-h coincubation at 37 degrees C suggests that the inhibitory activity is also nonproteolytic. That the activity is tissue specific is supported by the fact that extracts of gut, cardiac muscle, and diaphragm failed to block PRL release, whereas similarly prepared uterine extracts retained the ability to significantly depress PRL secretion. Haloperidol or bicuculline, dopaminergic and GABAergic receptor blockers, respectively, were ineffective in reversing the inhibitory effects of uterine extract on PRL secretion, suggesting that the inhibition is not due to dopamine or GABA. In addition to affecting basal release of PRL, in vitro larger doses of uterine extract were able to reverse the stimulatory effects of thyrotropin-releasing hormone on PRL secretion, indicating that the uterine-derived PRL inhibitory activity may also regulate stimulated PRL release. Taken together, these findings support the existence of a nondopaminergic, non-GABAergic inhibitory factor of uterine origin that specifically suppresses basal and stimulated secretion of PRL from cultured anterior pituitary cells.
Glucose-induced insulin secretion by perfused pancreas of 2- and 12-mo-old Fischer 344 rats
Authors: Curry D. L. , Reaven G. , Reaven E.
Published: December 2017

Previous studies have shown that cells from older Sprague-Dawley rats secrete insulin less efficiently in response to a maximal glucose challenge than do beta-cells from young animals. In the current study we have asked whether this change in beta-cell response occurs in another strain of rat, and, if so, whether the secretory defect occurs at submaximal as well as maximal glucose stimulatory levels. Pancreas perfusions were carried out on 2- and 12-mo-old Fischer 344 rats at perfusate glucose concentrations of 150 and 300 mg/dl. The secretory data for each pancreas was subsequently corrected for differences in islet cell mass and expressed as insulin secretion per unit islet cell. The results show that 12-mo-old Fischer rats release more insulin per total pancreas than do 2-mo-old animals at both glucose concentrations. However when corrected for islet cell mass, the amount of insulin secretion per islet cell is actually reduced in the older Fischer rat. These data are comparable to those seen previously in the 12-mo-old Sprague-Dawley rat and indicate that the insulin secretory defect seen as rats grow older is not species specific.
Vasopressin in plasma and cerebrospinal fluid of dogs during hypoxia or acidosis
Authors: Wang B. C. , Sundet W. D. , Goetz K. L.
Published: December 2017

Hypoxia and hypercapnia have been shown to cause an increase in the concentration of vasopressin in plasma, but their effects on vasopressin in cerebrospinal fluid (CSF) are not known. In addition, the effect of metabolic acidosis on plasma and CSF vasopressin has not been reported. In this study, plasma and CSF vasopressin levels were measured in anesthetized dogs subjected to either hypoxia, hypercapnia, or metabolic acidosis. Rate and depth of respiration were closely regulated with the aid of muscle paralysis and mechanical ventilation. Vasopressin increased markedly in both plasma and CSF during severe hypoxia (10% O2) and during hypercapnia (10% CO2) but did not change during either mild (15% O2) or moderate (12.5% O2) hypoxia. Although mild hypoxia by itself did not affect either plasma or CSF vasopressin, it did potentiate the increase in plasma and CSF vasopressin that was induced by severe hypercapnia, thus suggesting that hypoxia and hypercapnia may exert synergistic effects on vasopressin secretion. Metabolic acidosis produced by slow intravenous infusion of 1 N hydrochloric acid decreased arterial pH to values comparable to those induced by hypercapnia and increased vasopressin in plasma; CSF vasopressin was unchanged. These results are consistent with the concept that the source of vasopressin secreted into plasma may be different from that secreted into CSF.
Dihydropyridine calcium agonist and antagonist effects on aldosterone secretion
Authors: Kojima K. , Kojima I. , Rasmussen H.
Published: December 2017

The effects of the dihydropyridine calcium antagonists nimodipine, nitrendipine, and nisoldipine were studied on K+-induced and angiotensin II (ANG II)-induced aldosterone secretion from isolated calf adrenal glomerulosa cells. These drugs were more effective inhibitors of K+-induced secretion than ANG II-induced secretion. However, when the ANG II-induced release of intracellular calcium was blocked by prior treatment of cells with dantrolene, then nitrendipine was equally as effective in blocking ANG II- as K+-induced secretion. On the other hand, the dihydropyridine agonist, BAY K8644, was found to enhance K+-induced secretion to a greater extent than ANG II-induced secretion when the latter was studied in either the absence or presence of dantrolene. It is concluded that K+ and ANG II mobilize calcium from different sources for stimulus-response coupling in these cells and that there is no difference in the sensitivity to nitrendipine of the plasma membrane calcium channels operated by these two different agonists.
Glucagon, insulin, and growth hormone responses to glucose infusion in lactating dairy cows
Authors: Sartin J. L. , Cummins K. A. , Kemppainen R. J. , Marple D. N. , Rahe C. H. , Williams J. C.
Published: December 2017

Early lactation in the dairy cow is associated with an increased demand for energy that can only be met by hormone-mediated partitioning of nutrients. The purpose of this study was to determine adaptive responses of basal and glucose-stimulated glucagon (IRG), insulin (IRI), and growth hormone (GH) concentrations to early lactation. Blood was collected via jugular cannulas from nonpregnant nonlactating (NPNL) cows and cows 14 days antepartum (AP) and 5 and 30 days postpartum (PP). Basal concentrations of IRI decreased with lactation, IRG was essentially unchanged, and GH was increased with lactation. The molar IRI/IRG (I/G) ratio was decreased from 4.6 at day 14 AP to 1.3 at day 30 PP. The effects of exogenous glucose (0.56 mM/kg body wt) on IRI were greatest during pregnancy and declined with lactation. IRG responses to glucose were similar except in NPNL cows, which had a minimal but prolonged IRG inhibition, GH responses to glucose infusion were absent in NPNL cows and were most significant at 5 days PP. The decreased I/G and elevated GH concentrations suggests that both IRG and GH play a role in nutrient partitioning during early lactation.
Identification of the insulin receptor of cerebral microvessels
Authors: Haskell J. F. , Meezan E. , Pillion D. J.
Published: December 2017

Cerebral microvessels are known to possess receptors for insulin and have recently been shown to respond to physiological levels of this hormone. Scatchard analysis of binding data obtained with isolated cerebral microvessels gave curvilinear plots and showed that neonatal porcine cerebral microvessels have a greater number of insulin receptors per unit of protein than adult bovine cerebral microvessels. The high-affinity form of the insulin receptors of both neonatal porcine and adult bovine cerebral microvessels have similar binding constants (dissociation constant = 0.3 X 10(-9) M). Dissociation of 125I-insulin from cerebral microvessels was accelerated by the presence of unlabeled insulin in preparations from both neonatal pigs and adult cows. 125I-insulin was covalently cross-linked to its receptor in cerebral microvessels with disuccinimidyl suberate, and the hormone-receptor complex was isolated on sodium dodecyl sulfate-polyacrylamide gels. Under reducing conditions, 125I-insulin was found associated with a polypeptide with a molecular weight of 130,000, which is indistinguishable from the alpha-subunit of the liver insulin receptor. In contrast, nonvascular cerebral cortical tissue contained an insulin receptor with an alpha-subunit that was lower in molecular weight than the form isolated from cerebral cortical microvessels.
Function of vasopressinergic neurons in rats under conscious and anesthetized conditions
Authors: Cheng S. W. , North W. G.
Published: December 2017

The responses of vasopressinergic neurons to acute salt loading and to graded hemorrhage were studied in rats under conscious and anesthetized conditions. Chronically cannulated rats were used in this study so that pre- and postanesthetic conditions could be studied in the same animals. Anesthesia induced by a combination of ketamine hydrochloride and pentobarbital sodium (Nembutal) did not cause a release of vasopressin-associated neurophysin (VP-RNP). In response to infusion of 18% saline, animals in the anesthetized state had significantly greater increases in plasma osmolality (Posmol) and plasma sodium concentration than animals in the conscious state. However, the rate of increase in plasma VP-RNP concentration ([VP-RNP]) as well as the relationship between [VP-RNP] and Posmol were not significantly different for the two states. Graded hemorrhage caused similar rates of increase in [VP-RNP] for animals under conscious and anesthetized conditions. These data suggest that anesthesia induced by ketamine plus pentobarbital sodium does not change the responsiveness of vasopressinergic neurons to acute salt loading and to graded hemorrhage.
In vivo studies of hypoglycemia and lactic acidosis in endotoxic shock
Authors: Naylor J. M. , Kronfeld D. S.
Published: December 2017

Sheep were prepared with catheters in an artery and mesenteric, portal, and hepatic veins. Blood flows and metabolite concentration differences were measured across liver and gut. Net organ production rates were calculated for liver, portal drained viscera, and extrasplanchnic regions. Arterial glucose concentration rose for 2 h after endotoxin administration. The hyperglycemia was associated with increased hepatic glucose production. Hypoglycemia developed between 3 and 8 h when hepatic glucose production decreased closer to control values. Arterial glucagon concentrations rose to high levels during the hypoglycemic period. Neither hepatic blood flow or oxygen delivery limited glucose production; uptake of the gluconeogenic substrate lactate was reduced on some occasions. Glucose utilization was increased in shock. Portal glucose utilization accounted for 14.5% of nonhepatic glucose utilization. Increased portal glucose utilization was not related to plasma insulin concentrations or insufficient oxygen supply to the gut. Hyperglycemia drove glucose utilization. Although plasma insulin concentrations rose significantly in endotoxemia, the increase in pancreatic insulin output was much smaller and failed to attain statistical significance.
CSF vasopressin rhythm is effectively insulated from osmotic regulation of plasma vasopressin
Authors: Coleman R. J. , Reppert S. M.
Published: December 2017

By using our method for continuous removal of cisternal cerebrospinal fluid (CSF) and intermittent sampling of blood from unanesthetized freely moving cats, we investigated the effect of osmotic-induced changes in plasma vasopressin on the daily rhythm of CSF vasopressin. Examination of the daily profiles of vasopressin and osmolality in the CSF and plasma of six euhydrated animals showed that CSF vasopressin concentrations exhibit a clear daily rhythm, whereas CSF osmolality and plasma vasopressin and osmolality do not exhibit such daily variation. A 48-h period of water deprivation caused marked sustained elevations in plasma vasopressin concentrations, which returned to basal levels on rehydration. In contrast, water deprivation had only a small effect on the CSF vasopressin rhythm. Although there was a significant elevation of the normally low nighttime CSF vasopressin levels during water deprivation in three of the four animals studied, high daytime vasopressin levels were unaltered and the daily rhythm was clearly evident before, during, and after the period of water removal in all animals. Changes between plasma vasopressin and osmolality were significantly correlated in all animals. Changes between plasma and CSF osmolality were significantly correlated in three of the four animals. The data indicate that the circadian regulation of the CSF vasopressin rhythm is effectively insulated from the osmotic regulation of plasma vasopressin.