bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of secretion vesicle margination and lysis by glucose, IBMX, and glyburide
Authors: Draznin B. , Steinberg J. P. , Goodman M. , Leitner J. W. , Sussman K. E.
Published: December 2017

We have attempted to define the effect of glucose, glyburide, and isobutylmethylxanthine (IBMX) upon secretion vesicle margination to the plasma membrane and granule lysis. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors. Secretion vesicle lysis was studied by measuring insulin release into the incubation media. Our observations suggest that glucose directly affects both secretion vesicle margination and lysis. Both events are rapidly influenced by this secretagogue (within 10 min of incubation). Trifluoperazine (TFP) and removal of Ca2+ from the incubation media significantly reduced glucose-induced margination of secretion vesicles and their lysis (P less than 0.001). IBMX primarily influences the lysis of secretion vesicles and not their margination. IBMX caused a rapid increase in insulin secretion within 10 min without recruitment of SRIF receptors. Neither TFP nor the absence of extracellular Ca2+ affected IBMX-induced insulin release. Late enhancement in margination of secretion vesicles (30 min of incubation with IBMX) is probably related to the initial event of secretion vesicle lysis and is independent of extracellular calcium. Glyburide exerts its action in a manner similar to glucose, affecting both the lysis of secretion vesicles and their margination. However, the action of glyburide is independent of extracellular calcium and partially dependent upon calmodulin.
Epidermal growth factor measurements in mouse plasma: method, ontogeny, and sex difference
Authors: Perheentupa J. , Lakshmanan J. , Hoath S. B. , Beri U. , Kim H. , Macaso T. , Fisher D. A.
Published: December 2017

A highly sensitive mouse plasma (serum) epidermal growth factor (EGF) radioimmunoassay was utilized to determine EGF levels in mouse plasma and submandibular gland (SMG) at different ages. Plasma and serum levels were not different. Inferior vena caval blood was used because even at the age of 12 days EGF levels were markedly higher in neck blood. At 2 wk serum EGF levels were 60% of adult female levels. After a temporary decrease, mean EGF concentrations reached adult values at 31 and 60 days in the female but not yet in the male. In adults male serum EGF levels were twofold higher than female levels. This difference is parallel to but much smaller than the sex difference in SMG-EGF. SMG-EGF showed a very different ontogeny. Moreover, no correlation was present in the adults between the SMG and serum EGF concentrations. Testosterone treatment of adult females doubled their serum EGF levels, but the stimulated values were still below the mean of the male levels. The present observed plasma (serum) EGF levels in the mouse are 20-40% of previously reported values, probably because of the absence of EGF contamination from hair (urine) and milk.
Effects of exercise on insulin binding to human muscle
Authors: Bonen A. , Tan M. H. , Clune P. , Kirby R. L.
Published: December 2017

A procedure was developed to measure insulin binding to human skeletal muscle obtained via the percutaneous muscle biopsy technique. With this method the effects of exercise on insulin binding were investigated. Subjects (n = 9) exercised for 60 min on a bicycle ergometer at intensities ranging from 20-86% maximum O2 consumption (VO2max). Blood samples were obtained before, during, and after exercise and analyzed for glucose and insulin. Muscle samples (250 mg) for the vastus lateralis were obtained 30 min before exercise, at the end of exercise, and 60 min after exercise. Two subjects rested during the experimental period. There was no linear relationship between exercise intensities and the changes in insulin binding to human muscle. At rest (n = 2) and at exercise intensities below 60% VO2max (n = 5) no change in insulin binding occurred (P greater than 0.05). However, when exercise occurred at greater than or equal to 69% VO2max (n = 4), a pronounced decrement in insulin binding (30-50%) was observed (P less than 0.05). This persisted for 60 min after exercise. These results indicate that insulin binding in human muscle is not altered by 60 min of exercise at less than or equal to 60% VO2max but that a marked decrement occurs when exercise is greater than or equal to 69% VO2max.
Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats
Authors: James D. E. , Jenkins A. B. , Kraegen E. W.
Published: December 2017

The euglycemic hyperinsulinemic clamp technique in conscious unrestrained rats was used to examine the effect of insulin on glucose metabolism in metabolically distinct skeletal muscle in vivo. Tissue glucose metabolic rate (R'g) was estimated using 2-[3H]-deoxyglucose, and glucose disposal was examined by measuring glycogen content and [14C]glucose incorporation into glycogen in four different muscles. Insulin sensitivity varied among different muscle types in that the insulin concentration required for half-maximal stimulation of R'g was 80, 150, 280, and 320 mU/1 for soleus (SOL), red gastrocnemius (RG), white gastrocnemius (WG), and extensor digitorum longus, respectively. There were similar relative differences in the maximal effect of insulin on R'g in these muscles. Maximal insulin stimulation almost doubled muscle glycogen content in RG and SOL, whereas there was no change in WG. The relationship between R'g and glycogen synthesis indicated that increased glucose uptake resulted predominantly in glycogen storage. There was an excellent relationship between maximal R'g and blood flow in different muscles. We conclude that there is marked heterogeneity in insulin sensitivity and responsiveness among muscles of different fiber composition. Insulin-induced increases in total peripheral glucose disposal occur predominantly in muscles containing a high proportion of oxidative fibers. Therefore the relative proportion of oxidative to glycolytic muscle fibers may be important factors in determining whole body insulin sensitivity.
Methyl palmoxirate increases Ca2+-myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart
Authors: Dillmann W. H.
Published: December 2017

Previous studies have shown that in rats diabetes mellitus leads to a decrease in cardiac ventricle myosin V1 and an increase in myosin V3 levels. Insulin administration reverts myosin isoenzyme distribution to normal levels. It is currently unclear whether the effects of insulin on myosin isoenzyme distribution are a direct effect of the hormone or are mediated through insulin-induced alterations in cardiac metabolism. To gain further insight into this question diabetic rats received methyl palmoxirate, a potent inhibitor of long-chain fatty acid oxidation. Administration of 25 mg methyl palmoxirate X kg body wt-1 X day-1 to diabetic rats for 4 wk leads to a partial reversal of the effects of diabetes. Myosin V1 predominance is re-established and Ca2+-activated myosin ATPase activity increases by 60% (Ca2+-myosin ATPase normal rats 1.067 +/- 0.13 mumol Pi X mg protein-1 X min-1, diabetic rats 0.609 +/- 0.05 mumol Pi X mg protein-1 X min-1, diabetic + methyl palmoxirate rats 0.912 +/- 0.06 mumol Pi X mg protein-1 X min-1). The methyl palmoxirate-induced increase in myosin V1 levels and Ca2+-activated myosin ATPase activity occurred in the absence of changes in insulin and thyroid hormone levels. Methyl palmoxirate may have acted through its known inhibitory effect on cardiac beta-oxidation and/or the resultant stimulatory effect on glycolytic flux. Our findings may indicate that changes in cardiac substrate consumption can influence myosin isoenzyme predominance.
Time course of changes in albumin synthesis and mRNA in diabetic and insulin-treated diabetic rats
Authors: Peavy D. E. , Taylor J. M. , Jefferson L. S.
Published: December 2017

Albumin synthesis in rat liver in vivo decreased from 12.7 to 2.2% of total protein synthesis during the first 3 days after the induction of diabetes and then remained relatively constant at this depressed rate for another 3 days. Insulin treatment begun on the 3rd day after the induction of diabetes restored albumin synthesis to control values within 3 days. Hybridization of total polyadenylate-containing RNA with a specific albumin cDNA probe revealed a close correspondence between the relative abundance of albumin mRNA and the relative rate of albumin synthesis after induction of diabetes and in response to insulin treatment. The apparent half-life of albumin mRNA, based on the rate of change of the message from one steady-state level to another, was approximately 22 h in both diabetic and insulin-treated diabetic rats. Diabetes of 3-day duration had no effect on the average sizes of total and albumin-synthesizing polysomes or on the ribosomal half-transit time for total protein and albumin. However, the number of albumin-synthesizing polysomes decreased as a result of diabetes to approximately one-third the number found in control livers. Taken together the results indicate that albumin synthesis was regulated by the availability of albumin mRNA and not by alterations in degradation, sequestration, or translation of message.
Nonirritative lesions of VMH: effects on plasma insulin, obesity, and hyperreactivity
Authors: King B. M. , Frohman L. A.
Published: December 2017

Obesity resulting from lesions of the ventromedial hypothalamus (VMH) has often been attributed to ablation-induced disinhibition of insulin release. However, lesion studies have generally employed electrolyzing anodal current with stainless steel electrodes, which results not only in tissue ablation but deposits of metallic ions that can chronically irritate surrounding tissue. The present study compared the effects of irritative and nonirritative VMH lesions on plasma insulin levels and obesity in female rats. Blood samples were obtained after a 4-h fast and 17 min after the initiation of a meal (6 ml of sweetened milk in 7 min) during a period when VMH rats were food restricted to the level of sham-operated animals and again when all animals were fed ad libitum. Irritative lesions (anodal electrolytic with stainless steel electrodes) caused heavy metallic ion deposition at the lesion site, marked obesity, and hyperinsulinemia both during food restriction and ad libitum feeding. Nonirritative lesions (cathodal electrolytic with platinum electrodes) resulted in no metallic ion deposition in seven of nine animals. These seven rats, which displayed 65% of the weight gain of animals with irritative lesions (significantly greater than sham rats), had significantly elevated insulin levels only under the postabsorptive condition during ad libitum feeding. In addition, only the animals with irritative lesions displayed emotional hyperreactivity to capture and handling. It is concluded that obesity produced by anodal electrolytic lesions with stainless steel electrodes is a result of both a destructive component resulting in hyperphagia with secondary hyperinsulinemia and an irritative component (accounting for up to 40% of the weight gain in female rats) resulting in basal hyperinsulinemia independent of hyperphagia.(ABSTRACT TRUNCATED AT 250 WORDS)
A model for augmentation of hepatocyte response to pulsatile glucagon stimuli
Authors: Weigle D. S. , Koerker D. J. , Goodner C. J.
Published: December 2017

We have reported that in the physiological concentration range pulsatile glucagon delivery (6 pulses in 90 min) is a more effective stimulus of rat hepatocyte glucose production than is continuous infusion of the same amount of hormone (pulsatile EC50 = 186 +/- 41 pg/ml, continuous EC50 = 884 +/- 190 pg/ml). At supraphysiological glucagon concentrations, however, the maximal response to continuous glucagon infusion exceeds the response to pulses (241 +/- 14 vs. 140 +/- 11 mumol X G-1 X 90 min-1). In an effort to explain these observations we derived a model for the 90-min hepatocyte responses to pulsatile and continuous glucagon delivery based on the waveform of the hepatocyte response to a transient glucagon stimulus. The model demonstrated that the time constant for response decay was an important determinant of the relative efficacy of the two patterns of hormone delivery. For the observed decay constant value of 0.132 +/- 0.02 min-1 the model predicted the following dose-response parameters: pulsatile EC50 = 131 pg/ml, Rmax = 119 mumol X G-1 X 90 min-1, continuous EC50 = 656 pg/ml, Rmax = 272 mumol X G-1 X 90 min-1. The ability of a model based only on the kinetics of a single pulse to simulate the observed dose-response relationship suggests that pulsatile stimulation is intrinsically more effective than continuous hormonal stimulation.
Developmental changes of beta-adrenergic receptor-linked adenylate cyclase of rat liver
Authors: Katz M. S. , Boland S. R. , Schmidt S. J.
Published: December 2017

beta-Adrenergic agonist-sensitive adenylate cyclase activity and binding of the beta-adrenergic antagonist(-)-[125I]iodopindolol were studied in rat liver during development of male Fischer 344 rats ages 6-60 days. In liver homogenates maximum adenylate cyclase response to beta-adrenergic agonist (10(-5) M isoproterenol or epinephrine) decreased by 73% (P less than 0.01) between 6 and 60 days, with most of the decrease (56%; P less than 0.01) occurring by 20 days. beta-adrenergic receptor density (Bmax) showed a corresponding decrease of 66% (P less than 0.01) by 20 days without subsequent change. Binding characteristics of stereospecificity, pharmacological specificity, saturability with time, and reversibility were unchanged with age. GTP-, fluoride-, forskolin-, and Mn2+-stimulated adenylate cyclase activities also decreased during development, suggesting a decrease of activity of the catalytic component and/or guanine nucleotide regulatory component of adenylate cyclase. These results indicate that the developmental decrease of beta-adrenergic agonist-sensitive adenylate cyclase activity may result from decreased numbers of beta-adrenergic receptors. Developmental alterations of nonreceptor components of the enzyme may also contribute to changes of catecholamine-sensitive adenylate cyclase.
Binding protein for vitamin D and its metabolites in rat mesenteric lymph
Authors: Dueland S. , Bouillon R. , Van Baelen H. , Pedersen J. I. , Helgerud P. , Drevon C. A.
Published: December 2017

A protein with high affinity for vitamin D3 and 25-hydroxyvitamin D3 in rat mesenteric lymph has been studied. Mesenteric lymph was collected after duodenal instillation of radiolabeled vitamin D3 and 25-hydroxyvitamin D3. As previously described, approximately 10% of vitamin D3 (S. Dueland, J.I. Pedersen, P. Helgerud, and C.A. Drevon, J. Biol. Chem. 257: 146-150, 1982) and 95% of 25-hydroxyvitamin D3 (S. Dueland, J.I. Pedersen, P. Helgerud, and C.A. Drevon, Am. J. Physiol. 245 (Endocrinol. Metab. 8): E463-E467, 1983) recovered in mesenteric lymph were associated with the alpha-globulin fractions. The radioactive vitamin D3 recovered in the lymph fraction with d greater than 1.006 (free of chylomicrons) coeluted with purified rat serum binding protein for vitamin D and its metabolites (DBP) from an antirat DBP column. The results obtained by immunoblotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that this protein in mesenteric lymph had molecular weight and immunological properties identical with purified serum DBP. Purified serum DBP labeled with 125I was injected intravenously and mesenteric lymph was collected. in lymph, suggesting that DBP may be transferred from blood to mesenteric lymph and that plasma and lymph DBP may have a similar origin.
Human adipose tissue lipoprotein lipase: changes with feeding and relation to postheparin plasma enzyme
Authors: Iverius P. H. , Brunzell J. D.
Published: December 2017

An assay procedure using three different methods to recover lipoprotein lipase (LPL) activity from biopsy specimens of human adipose tissue has been developed. Elution of enzyme from small pieces of tissue was performed at 4 and 37 degrees C using a physiological buffer containing heparin and serum. Extraction of enzyme from a tissue homogenate was carried out in the presence of detergent (sodium deoxycholate and Nonidet P-40), which markedly improved the recovery of enzyme activity. It is suggested that elution at 4 degrees C represents extracellular enzyme activity only and therefore theoretically is the closest measure of physiologically active LPL on vascular endothelium, whereas elution at 37 degrees C, in addition, reflects some intracellular enzyme secreted during the incubation period. In female subjects of various relative body weights activity eluted at 37 degrees C as well as detergent-extracted activity were highly correlated with the extracellular activity eluted at 4 degrees C (r = 0.9). Furthermore, all three parameters correlated strongly with LPL activity in post-heparin plasma, suggesting that they are valid indices of physiologically active LPL. The regression of LPL activity in plasma after a 60-min heparin infusion on adipose tissue LPL yielded higher correlation coefficients for activities recorded after elution at 4 and 37 degrees C (r = 0.725 and 0.754, respectively) than for detergent extraction (r = 0.607). Moreover, the increment of adipose tissue LPL after feeding was approximately twice as high for the activity eluted at 4 and 37 degrees C (34%) as for detergent-extracted activity (19%).(ABSTRACT TRUNCATED AT 250 WORDS)
Direct effect of insulin on albumin gene expression in primary cultures of rat hepatocytes
Authors: Flaim K. E. , Hutson S. M. , Lloyd C. E. , Taylor J. M. , Shiman R. , Jefferson L. S.
Published: December 2017

The purpose of this study was to identify a cell culture system in which the role of insulin in regulating albumin gene expression could be investigated. The system selected was rat hepatocytes maintained in primary culture in a chemically defined, serum-free medium. Under control conditions albumin secretion was nearly the same as the rate recorded in vivo and in perfused liver and was reasonably well maintained during 8 days of culture. Deletion of insulin from the culture medium for 3-6 days resulted in 40-60% reductions in albumin secretion. Furthermore, albumin secretion relative to the rate of total protein synthesis was reduced by approximately 50% as a result of insulin deficiency. Readdition of the hormone to insulin-deficient cultures restored secretion to the control rate. A maximal effect of insulin was observed within 3 days after readdition of the hormone, and a half-maximal response was obtained with a hormone concentration of approximately 3.0 nM. The relative abundance of albumin mRNA, as measured by solution hybridization using a complementary DNA probe, responded in a parallel fashion to the changes in albumin secretion. Thus rat hepatocytes maintained under appropriate culture conditions reflect the effects of diabetes and insulin treatment on albumin gene expression observed in vivo and provide an excellent model system in which to study the mechanism(s) of insulin action.
Disk method for measuring effects of neurohypophysial hormones on urea permeability of toad bladder
Authors: Eggena P.
Published: December 2017

This study describes a precise and sensitive method for the bioassay of 8-arginine vasotocin (AVT). The technique is based on the observation that AVT increases the permeability to urea of the isolated toad bladder and that this effect can be measured with minute quantities of AVT by suspending bladders in humid air and applying hormone on small paper disks. The hormone diffuses from the disk to the underlying epithelium where it increases permeability to urea. The bladder is filled with Ringer's fluid containing [14C]urea and the label diffuses across the bladder wall into the disk at the serosal surface. Disks are removed at timed intervals for scintillation counting. Disks containing 0.25 pg AVT accumulated 232 +/- 8 cpm of [14C]urea in 30 min, whereas control disks without hormone at a distance of 3-4 mm on the same bladder wall accumulated only 12 +/- 2 cpm. The minimal sensitivity during the summer was 0.1 pg AVT. Average values (+/- SE) for induction of a half-maximal urea permeability response in toads from all seasons were 1.4 +/- 0.3 X 10(-10) M for AVT, 7.4 +/- 1.5 X 10(-9) M for 8-arginine vasopressin, and 2.9 +/- 0.6 X 10(-8) M for oxytocin. Plasma from a hydrated toad (255 mosm/kg H2O) showed AVT-like activity of 1.53 X 10(-11) M and from a dehydrated toad (342 mosm/kg H2O) 4.86 X 10(-11) M. Because this bioassay is specific and as sensitive as the radioimmunoassay, it may serve as a useful tool for studying the physiology of vasotocin.
Enteral versus parenteral nutrition: comparison of energy metabolism in healthy subjects
Authors: Vernet O. , Christin L. , Schutz Y. , Danforth E. , Jequier E.
Published: December 2017

Continuous respiratory exchange measurements were performed on 10 healthy young women for 1 h before, 3 h during, and 3 h after either parenteral (iv) or intragastric (ig) administration of a nutrient mixture (52% glucose, 18% amino acid, and 30% lipid energy) infused at twice the postabsorptive resting energy expenditure (REE). REE rose from 0.98 +/- 0.02 (iv) and 0.99 +/- 0.02 kcal/min (ig) postabsorptively to 1.13 +/- 0.03 (iv) and 1.13 +/- 0.02 kcal/min (ig), resulting in nutrient-induced thermogenesis of 10 +/- 0.6 and 9.3 +/- 0.9%, respectively, when related to the metabolizable energy. The respiratory quotient rose from preinfusion values of 0.81 +/- 0.02 (iv) and 0.80 +/- 0.01 (ig) to 0.86 +/- 0.01 (iv) and 0.85 +/- 0.01 (ig). After nutrient administration the respiratory quotient fell significantly to below the preinfusion values. Plasma glucose and insulin concentrations rose during nutrient administration but were higher during the intravenous route. It is concluded that, although the response time to intragastric administration was delayed, the thermic effects and overall substrate oxidations were comparable during intravenous or intragastric administration, albeit, at lower plasma glucose and insulin concentrations via the intragastric route.
Pituitary-adrenal function after transplantation in rats: dependence on age of the adrenal graft
Authors: Engeland W. C.
Published: December 2017

Comparisons of resting plasma adrenocorticotropin (ACTH) and corticosterone in the morning and afternoon were made among adult rats bearing regenerated adult adrenal grafts, neonatal (day 1) adrenal grafts, adult adrenal capsule grafts, or intact adrenals. In the morning plasma ACTH and corticosterone were similar in all rats. In the afternoon, plasma ACTH was elevated in rats bearing neonatal adrenal grafts or adult adrenal capsule grafts, but not in rats bearing whole adult adrenal grafts. There was no difference in afternoon plasma corticosterone among rats bearing transplanted adrenals, although afternoon plasma corticosterone was decreased in rats bearing transplants compared with rats with intact adrenals. Thus the increased plasma ACTH after adrenal transplantation cannot be explained entirely by decreases in resting plasma corticosterone. Adrenal responsiveness to ACTH was tested at 5 wk after transplantation in the afternoon by measuring the plasma corticosterone response to submaximal doses of ACTH. The responsiveness was decreased in rats bearing transplants. In addition, responsiveness was inversely related to the age of the grafted adrenal tissue. Adrenals regenerated from adult adrenals were more responsive than adrenals regenerated either from neonatal adrenals or from adult adrenal capsules. The findings suggest that following adrenal transplantation reestablishment of normal pituitary-adrenocortical function does not occur in rats bearing adrenals regenerated from immature adrenal cells. In addition, comparable alterations occur after regeneration of adrenal tissue from neonatal adrenal cells and adult adrenal capsular cells. Elevated plasma ACTH associated with adequate plasma corticosterone in rats bearing adrenals regenerated from immature adrenal cells may result from chronic alteration in responsiveness to steroid feedback.(ABSTRACT TRUNCATED AT 250 WORDS)
Regional ketone body utilization by rat brain in starvation and diabetes
Authors: Hawkins R. A. , Mans A. M. , Davis D. W.
Published: December 2017

The rate of ketone body (beta-hydroxybutyrate and acetoacetate) metabolism was measured in individual cerebral structures of fed, starved, and diabetic rats. This was done by infusing beta-[3-14C]hydroxybutyrate intravenously and measuring the incorporation of 14C into brain by quantitative autoradiography. The capacity of the brain to use ketone bodies, expressed as plasma clearance, increased in starvation and diabetes by approximately 50-60%. Plasma clearance was near maximal after 2 days starvation and was not significantly increased after 4 days starvation, 6 days of diabetes or 28 days of diabetes. In all situations the ketone bodies provided only a modest amount of fuel for brain energy metabolism; 3.2% after 2 days starvation and 6.5 and 9.9% after 6 and 28 days of diabetes. The fraction of their energy requirement which the various structures could derive from the ketone bodies differed widely. In general the telencephalon made greatest use of ketone bodies, whereas the hindbrain used least. There was no correlation between the energy requirement of structures (estimated from glucose use in fed rats) and the fraction of energy they could derive from ketone bodies.
Glutamine blocks lipolysis and ketogenesis of fasting
Authors: Cersosimo E. , Williams P. , Hoxworth B. , Lacy W. , Abumrad N.
Published: December 2017

Several in vivo studies have indirectly suggested a relationship between blood glutamine and ketonemia. The present study was designed to characterize the role glutamine plays in regulating lipolysis and ketogenesis during fasting in vivo. Twelve dogs had catheters implanted in the hepatic and portal veins (V) and in the femoral artery (A) 17-21 days before study. The animals were fasted for 4 days. After a 120-min rest and 40-min basal periods, 6 dogs received an infusion of L-glutamine at 6 mumol X kg-1 X min-1 and 6 received saline and acted as controls. Hepatic and splanchnic balances (mumol X kg-1 X min-1) were estimated by A-V differences multiplied by blood flow determined by indocyanine green. Fasting was associated with a compensated (no change in pH) mild metabolic acidosis but no change in plasma insulin and glucagon or blood glutamine. L-Glutamine infusion increased blood glutamine by 20% but decreased arterial free fatty acids (FFA, from 1,054 +/- 47 to 850 +/- 43 mumol/l, P less than 0.01), beta-hydroxybutyrate (beta-OHB, from 136 +/- 15 to 66 +/- 8 mumol/l, P less than 0.01), acetoacetate (AcAc, from 168 +/- 26 to 86 +/- 21 mumol/l, P less than 0.01), and glycerol (from 90 +/- 4 to 65 +/- 5 mumol/l, P less than 0.01). It also decreased hepatic uptake of glycerol (from 2.5 +/- 0.5 to 0.8 +/- 0.3 mumol X kg-1 X min-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of ovarian sex steroids on osmoregulation and vasopressin secretion in the rat
Authors: Barron W. M. , Schreiber J. , Lindheimer M. D.
Published: December 2017

Effects of sex steroids on osmoregulation were studied in intact and ovariectomized Sprague-Dawley rats treated for 2 wk with subcutaneously implanted hormone pellets containing 0.5 mg 17 beta-estradiol (E2) alone (group 1) or combined with 50 mg progesterone (PG; group 2) and 5.0 mg E2 alone (group 3) combined with PG (group 4). An additional group (5) of animals was given 14 daily injections with 100 micrograms/100 g body weight of E2. Controls for each group received vehicle alone. There were no alterations in basal plasma osmolality (Posmol) or vasopressin (PAVP), except for group 3 in which a small (2.5 mosmol/kg) decrement in Posmol was observed. However, mean PNa was decreased (0.9-3.4 meq/l) in hormone-treated rats, and alterations in Pglucose and/or Purea could not explain the Na-osmolal discrepancy. Intraperitoneal hypertonic saline resulted in stepwise increases in both Posmol and PAVP. Regression analysis of PAVP on Posmol demonstrated similar osmotic thresholds for AVP release in estrogen and control rats, but the slope (sensitivity of the response) was significantly (P less than 0.005) greater in hormone-treated animals. In contrast, the PAVP response to isosmotic volume depletion was not altered by estrogen. The enhanced response to osmotic stimuli could not be explained by alterations in plasma volume or pituitary AVP content and differed from PAVP -Posmol relationships observed by us previously in gravid rats. In other experiments Posmol and PAVP were similar during all stages of the estrus cycle, while Posmol was approximately equal to 10 mosmol/kg lower in 21-day gravid rats. These data demonstrate that, although estradiol has little effect on basal osmoregulation or hemodynamically mediated AVP release, PAVP responses to osmotic stimuli are markedly enhanced. These osmoregulatory effects, however, differ from those observed during rodent gestation.
By 95 days of gestation CRF increases plasma ACTH and cortisol in ovine fetuses
Authors: Hargrave B. Y. , Rose J. C.
Published: December 2017

Plasma adrenocorticotropin (ACTH) and cortisol (F) responses to 15-min intravenous infusions of synthetic ovine corticotropin-releasing factor (CRF) were measured by radioimmunoassay in three groups of chronically cannulated ovine fetuses. Fetuses (n = 7) in group I were 107 +/- 2 days gestation (0.72 G) and fetuses (n = 7) in group II were 126 +/- 2 days gestation (0.86 G). Group III fetuses (n = 5) were studied at 5-day intervals during the last 2 wk of gestation. Resting fetal plasma ACTH levels were not significantly different among the three experimental groups. Infusions of CRF (50 ng X kg-1 X min-1) provided similar, significant increases in fetal plasma ACTH concentrations in the three groups. In the young fetuses (group I) the ACTH responses to 500 ng X kg-1 X min-1 infusions of CRF were greater than responses to 50 ng X kg-1 X min-1 infusions P less than 0.001. In group II both doses of CRF produced equivalent increases in ACTH that were comparable with the responses to 50 ng X kg-1 X min-1 infusions in Group I. This suggests that fetal ACTH responsiveness to large doses of CRF decreases between 0.72 and 0.86 G. Resting fetal plasma F levels increased during gestation (P less than 0.01). There was an F response (P less than 0.001) to CRF in all groups with greater responses observed in the older fetuses. This suggests that fetal adrenal responsiveness to ACTH or other peptides released by CRF increases during gestation.
In vitro exhaustion of pancreatic beta-cells
Authors: Hoenig M. , MacGregor L. C. , Matschinsky F. M.
Published: December 2017

To learn more about possible limited beta-cell secretory capacity and factors essential for insulin release, a perifusion system was applied that allowed the in vitro study of insulin secretion from isolated pancreatic islets for more than 6 h. Islets isolated from rats were stimulated with various glucose concentrations (7.5, 16.7, and 30 mM), alpha-ketoisocaproate (30 mM), and 30 mM glucose plus 1 mM 3-isobutyl-1-methylxanthine for several hours in Krebs-Ringer-bicarbonate buffer (KRB) or RPMI 1640. Islets showed "exhaustion" with all stimulatory conditions used when KRB was the perifusion medium. This was not prevented by addition of amino acids, phosphate, myo-inositol or arachidonic acid. With RPMI 1640 as the basal medium, exhaustion was not seen at 7.5 mM but was readily approached at higher glucose concentrations. It is possible that the exhaustion phenomenon observed here is due to a depletion of a readily releasable insulin pool.
Influence of calcium and other divalent cations on protein turnover in rat skeletal muscle
Authors: Baracos V. , Greenberg R. E. , Goldberg A. L.
Published: December 2017

When rat muscles were incubated in Ca2+-free media, their rates of protein break-down were significantly lower than in complete medium (2.58 mM Ca2+). Dantrolene and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, inhibitors of Ca2+ release from the sarcoplasmic reticulum, also reduced muscle proteolysis. When Ca2+ was added (up to 5.16 mM), proteolysis increased progressively up to 70% in the intact soleus and extensor digitorum longus muscles and up to 300% in the cut diaphragm preparation. Addition of Ca2+ did not affect the muscles' ATP or phosphocreatine content and increased protein synthesis slightly or not at all. Sr2+, Ba2+, and Mn2+ also increased proteolysis, but were less effective than Ca2+. Mg2+ inhibited the enhancement of proteolysis by Ca2+. This stimulation by Ca2+ was not affected by inhibitors of voltage-dependent Ca2+ channels, calmodulin, metalloendoproteases, microfilament or microtubule formation, or mersalyl. High Ca2+ levels also increased prostaglandin (PG) E2 production, although a rise in PGE2 did not appear essential for the increased proteolysis. The proteolysis induced by Ca2+ was prevented in muscles treated with Ep-475 or leupeptin. By contrast, these inhibitors of thiol proteases did not affect protein breakdown in Ca2+-free medium. Thus extracellular Ca2+ activates and Mg2+ inhibits a proteolytic pathway involving thiol proteases.
Halothane is less suppressive than pentobarbital on reflex and neural activation of pancreatic F-cell
Authors: Havel P. J. , Paquette T. L. , Taborsky G. J.
Published: December 2017

To determine the suitability of halothane anesthesia for studies of parasympathetic control of the endocrine pancreas in dogs, we assessed the effect of halothane on reflex, direct neural, and direct chemical activation of the parasympathetic input to the islet. Levels or output of pancreatic polypeptide (PP), an islet hormone under predominant cholinergic influence, were used as an indicator of the degree of parasympathetic activation and its potential suppression by anesthesia. Reflex stimulation of the parasympathetic nervous system by 2-deoxy-D-glucose (2-DG) in dogs anesthetized with halothane (0.8%) caused a fourfold increase in plasma PP levels, equivalent to the response in conscious dogs. In contrast, 2-DG at this dose and at a threefold higher dose did not alter PP levels in dogs anesthetized with pentobarbital (30 mg/kg iv), suggesting that halothane at this dose is not suppressive and that pentobarbital is very suppressive on reflex activation of the parasympathetic nerves to the pancreas. Bilateral electrical stimulation of the cervical vagi in halothane-anesthetized dogs elicited a sixfold increase in the pancreatic output of PP. The same stimulation caused only a twofold increase of PP output in pentobarbital-anesthetized dogs. These data suggests that halothane is also less inhibitory than pentobarbital on either peripheral neurotransmission or pancreatic F-cell responsiveness. The effect of direct activation of the F-cell by bethanechol did not differ between the two anesthesias. Therefore, the attenuated PP response to vagal stimulation in pentobarbital-anesthetized dogs is probably due to an action of pentobarbital on peripheral neurotransmission, perhaps at the intrapancreatic parasympathetic ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)
Additive effects of prior exercise and insulin on glucose and AIB uptake by rat muscle
Authors: Zorzano A. , Balon T. W. , Goodman M. N. , Ruderman N. B.
Published: December 2017

After exercise of moderate intensity the ability of insulin to stimulate the uptake of glucose and alpha-aminoisobutyric acid (AIB) in perfused rat muscle is enhanced in a parallel fashion. The present study was designed to examine the effect of intense exercise on the subsequent uptake of these substrates. For this purpose, rats fed ad libitum were run on a treadmill for 50 min at high intensity and glucose and AIB uptake by muscle were then assessed in the isolated perfused hindquarter preparation. In confirmation of previous studies, 30 min after such exercise the absolute rate of glucose uptake in the presence of 20,000 microU/ml of insulin was greater due to additive effects of insulin and prior exercise. A novel finding was that 150 min postexercise the rate of glucose uptake was still increased in the presence of a supramaximal concentration of insulin, but entirely due to an increase in insulin responsiveness. The uptake of AIB and its response to insulin in general paralleled that of glucose. The results indicate that both glucose and AIB uptake by skeletal muscle in the presence of a supramaximal concentration of insulin are increased after intense exercise. They suggest that this is initially due to an additive effect of insulin and exercise and later due to an increase in insulin responsiveness. The findings are compatible with the notion that after exercise insulin is able to recruit or activate glucose (and possibly AIB) transporters in muscle, that it does not affect in the resting state.
Central cholinergic control of vasopressin release in conscious rats
Authors: Iitake K. , Share L. , Ouchi Y. , Crofton J. T. , Brooks D. P.
Published: December 2017

Intracerebroventricular (icv) administration of carbachol into conscious rats evoked a substantial increase in vasopressin secretion and blood pressure in a dose-dependent manner. These effects were blocked by pretreatment with the muscarinic blocker, atropine (10 micrograms icv), but not by the nicotinic blocker, hexamethonium (10 micrograms icv). Hexamethonium did, however, block the increase in blood pressure, the decrease in heart rate, and the very small elevation in the plasma vasopressin concentration induced by nicotine (10 micrograms icv). These results indicate that stimulation of either central nicotinic or muscarinic receptors can affect the cardiovascular system and suggest that the cholinergic stimulation of vasopressin secretion may involve primarily muscarinic receptors in the conscious rat.
Maternal ethanol ingestion: effect on maternal and neonatal glucose balance
Authors: Witek-Janusek L.
Published: December 2017

Liver glycogen availability in the newborn is of major importance for the maintenance of postnatal blood glucose levels. This study examined the effect of maternal ethanol ingestion on maternal and neonatal glucose balance in the rat. Female rats were placed on the Lieber-DeCarli liquid ethanol diet, an isocaloric liquid pair-fed diet, or an ad libitum rat chow diet at 3 wk before mating and throughout gestation. Blood and livers were obtained from dams and rat pups on gestational days 21 and 22. The pups were studied up to 6 h in the fasted state and up to 24 h in the fed state. Maternal ethanol ingestion significantly decreased litter size, birth weight, and growth. A significantly higher mortality during the early postnatal period was seen in the prenatal ethanol exposed pups. Ethanol significantly decreased fed maternal liver glycogen stores but not maternal plasma glucose levels. The newborn rats from ethanol ingesting dams also had significantly decreased liver glycogen stores. Despite mobilizing their available glycogen, these prenatal ethanol exposed pups became hypoglycemic by 6 h postnatal. This was more marked in the fasted pups. Ethanol did not affect maternal nor neonatal plasma insulin levels. Thus maternal ethanol ingestion reduces maternal and neonatal liver glycogen stores and leads to postnatal hypoglycemia in the newborn rat.
Insulin-enhanced thermogenesis in skeletal muscle after exercise: regulatory factors
Authors: Balon T. W. , Zorzano A. , Goodman M. N. , Ruderman N. B.
Published: December 2017

Insulin increases O2 consumption by 25-30% in perfused rat muscle following intense exercise. The object of the present study was to characterize further the basis for this finding. Toward this end, O2 consumption was measured in the perfused hindquarter of rats either following a treadmill run or muscle contractions induced by electrical stimulations of the sciatic nerve. The results indicate that the increase in O2 consumption induced by insulin varies with the intensity of exercise, that it is initiated by factors generated locally rather than systemically, and that it is not attenuated by alpha or beta-adrenergic blockade. The results also demonstrated that the increase in O2 consumption is substantially diminished if glucose is not added to the perfusion medium.
Effects of energy deprivation on sex hormone patterns in healthy menstruating women
Authors: Kurzer M. S. , Calloway D. H.
Published: December 2017

To determine whether short-term energy deprivation affects sex hormone patterns, six healthy women were studied for two menstrual cycles. Two diets containing recommended levels of all nutrients and differing substantially only with respect to energy content were provided in sequence. During the first cycle, energy intake was 40 +/- 2 kcal/kg body weight, and weight was essentially constant. For the second cycle, energy intake was reduced to 41% of the original intake, averaging 17 +/- 1 kcal/kg initial body weight. During the low-energy diet, weight loss ranged from 3.2 to 6.7 kg. The two leanest women, who also lost the most weight, became anovulatory and amenorrheic in the low-energy period. Within a specific phase of cycle, however, the diet did not affect concentrations of estradiol, progesterone, luteinizing hormone, or follicle-stimulating hormone. Testosterone and androstenedione levels peaked midcycle normally and were decreased with the low-energy diet, while levels of sex hormone-binding globulin increased and those of dehydroepiandrosterone sulfate did not change. These results demonstrate short-term dietary and body composition effects on the menstrual cycle and serum androgens.
Adipocyte glycogen synthase and pyruvate dehydrogenase in obese and type II diabetic subjects
Authors: Mandarino L. J. , Madar Z. , Kolterman O. G. , Bell J. M. , Olefsky J. M.
Published: December 2017

To determine whether 1) insulin stimulates pyruvate dehydrogenase (PDH) and glycogen synthase (GS) in isolated human adipocytes and 2) adipocytes from subjects with obesity or noninsulin-dependent diabetes mellitus (NIDDM) are resistant to the effects of insulin, PDH and GS were assayed in adipocytes from 11 control, 8 obese, and 9 NIDDM subjects. Basal PDH activities were 123 +/- 20, 129 +/- 21, and 128 +/- 25 pmol pyruvate oxidized/min per 2 X 10(5) adipocytes in these groups. Insulin stimulated PDH activity to a maximum of 223 +/- 38 pmol/min per 2 X 10(5) in adipocytes from control subjects, but did not significantly increase values from obese subjects. Insulin significantly decreased PDH activity in cells from NIDDM subjects (99 +/- 20 pmol/min per 2 X 10(5) cells, P less than 0.05). PDH activity assayed with high magnesium and calcium concentrations was significantly stimulated by insulin in adipocytes from control, but not obese or NIDDM subjects. GS assayed with 1 mM glucose 6-phosphate did not differ significantly among control, obese, or NIDDM subjects (446 +/- 110, 451 +/- 156, and 291 +/- 35 pmol incorporated into glycogen, respectively). Insulin significantly stimulated glycogen synthase in all three groups (827 +/- 179, 764 +/- 177, and 569 +/- 51 pmol incorporated) to a similar extent. Glycogen synthase assayed with 10 mM glucose 6-phosphate was decreased in NIDDM (1,335 +/- 131 pmol incorporated) compared with obese or control subjects (2,512 +/- 451 and 2,239 +/- 230 pmol incorporated, respectively, P less than 0.01).
Antishock effects of corticosterone on dextran-induced shock in rats
Authors: Kogure K. , Ishizaki M. , Nemoto M. , Nakamura T. , Suzuki M.
Published: December 2017

To study the effects of glucocorticoid on the shock state, dextran-induced shock in rats was used as an experimental model system. The rats were divided into three groups, viz., control (group A), adrenalectomized (group B), and adrenalectomized corticosterone supplemented (2 mg/rat for 4 days; group C), and 5% dextran solution was given intravenously to each rat. In group B, remarkable increases in the histamine levels in both plasma and the paw cutaneous tissue, hemoconcentration, and intractable hypotension were observed. Most rats in group B died during the shock experiment without showing any recovery when the cannulas were inserted into the left carotid artery for the measurement of blood pressure. But in group C, most rats eventually survived and recovered to a normal state within 2 h, so that corticosterone clearly ameliorated the shock state of adrenalectomized rats by dextran administration. These results suggested that the ameliorating effects of corticosterone in the dextran-induced shock states are due to the acceleration of the rate of clearance of circulating chemical mediators that are represented by histamine and are due to the alteration of overall responsiveness of the animals to a complex array of factors that threaten the status of the animals, as represented by the amelioration of the vascular activity.
Uptake, distribution, and excretion of 31silicon in normal rats
Authors: Adler A. J. , Etzion Z. , Berlyne G. M.
Published: December 2017

This study examines the uptake, distribution, and excretion of 31-labeled silicic acid in rat tissues at 1, 2, and 4 h after intracardiac injection of 31Si(OH)4. Plasma levels of 31Si decrease rapidly from 0.71 +/- 0.04% at 1 h to 0.07 +/- 0.06% of the dose administered per milliliter at 4 h. 31Si in plasma was found to be virtually entirely nonprotein bound. Kidney, liver, and lung accumulated the greatest amounts of 31Si per gram of wet weight, with concentrations at 4 h suggesting both relatively avid uptake and retention. Bone, skin, spleen, muscle, and testes also accumulated 31Si, but the levels were considerably lower than the aforementioned organs. Brain, however, contained negligible concentrations of 31Si throughout the study, indicating active exclusion by the blood-brain barrier. The major portion of the administered 31Si, 77 +/- 12%, was recovered in the urine within 4 h.
A serum protease cleaves proANF into a 14-kilodalton peptide and ANF
Authors: Bloch K. D. , Zisfein J. B. , Margolies M. N. , Homcy C. J. , Seidman J. G. , Graham R. M.
Published: December 2017

Proatrial natriuretic factor (proANF), the 126-amino acid precursor of ANF, is the major storage form in mammalian atria. In contrast, two ANF peptides containing the 28- and 24-carboxyterminal residues of proANF have been isolated from rat plasma. Whether the cleavage of proANF in vivo to these ANF peptides occurs during or after its release into the circulation has not been determined. The latter possibility was suggested by our previous study where, by using a cultured rat cardiocyte preparation, we demonstrated that proANF is secreted intact into the culture medium. We now report that serum, but not plasma, contains a protease that specifically cleaves the 17-kdalton proANF to a 14-kdalton amino-terminal peptide and the carboxyterminal 3-kdalton circulating forms of ANF. The role of this proANF-cleaving enzyme in the generation of the biologically active ANF peptides remains to be defined. Its isolation and characterization should provide insights into its site of production and whether in vivo it is involved in the processing of circulating proANF.