Influences of exogenous insulin on arterial blood pressure measurements of the rat

Studies were undertaken with adult male rats to test the hypothesis that euglycemic hyperinsulinemia would alter mean arterial blood pressure (MAP) and heart rate (HR) relationships by activation of the sympathetic nervous system. Conscious rats were infused either with insulin or control vehicle (0, 0.47, 1.5, 4.7, 15.0 mU.kg-1.min-1) for 75 min before injection of hexamethonium. Compared with the control period, insulin infusion significantly increased MAP by 7.1 +/- 0.1, 12.7 +/- 2.0, and 19.7 +/- 0.3 (SE) mmHg and HR by 44 +/- 8.4, 66 +/- 10.3, and 95 +/- 6.3 beats/min, respectively, during the three highest rates of infusion. The dose-dependent increases in MAP and HR were due to increases in the activity of hexamethonium-sensitive pathways. In chemically sympathectomized rats, insulin infusion did not produce a significant increase in either MAP or HR. The influence of exogenous norepinephrine on MAP and HR was also studied after insulin infusion. Compared with the insulin-vehicle infusion, insulin infusion significantly depressed (P less than 0.05) the norepinephrine dose-response increase in MAP. In addition, isolated smooth muscle strips were studied to determine the influence of insulin on their in vitro responses to increasing doses of norepinephrine. Although insulin did not alter contractility, it significantly (P less than 0.05) decreased the sensitivity of the vascular strips to norepinephrine. Collectively, the data from these euglycemic experiments indicated that infusions of insulin caused increases in HR and MAP because of activation of the sympathetic nervous system, even though the responsiveness of the vascular smooth muscle was depressed.     

Diminished hormonal responses to exercise in trained rats

Male rats (120 g) either were subjected to a 12-wk physical training program (T rats) or were sedentary controls (C rats). Subsequently the rats were killed at rest or after a 45- or 90-min forced swim. At rest, T rats had higher liver and muscle glycogen concentrations but lower plasma insulin. During exercise, blood glucose increased 60% in T rats but decreased 20% in C rats. Plasma glucagon and insulin concentrations did not change in T rats but plasma glucagon increased and insulin decreased markedly in C rats. Plasma epinephrine (90 min: range, 0.78-2.96 ng-ml-1, (T) vs. 4.42-15.67 (C)) and norepinephrine (90 min: 0.70-2.22 (T) vs. 2.50-6.10 (C)) were lower in T than in C rats. Hepatic glycogen decreased substantially and, as with muscle glycogen, the decrease was parallel in T and C rats. The plasma concentrations of free fatty acids were higher but lactate and alanine lower in T than in C rats. In trained rats the hormonal response to exercise is blunted partly due to higher glucose concentrations. In these rats adipose tissue sensitivity to catecholamines is increased, and changes in glucagon and insulin concentrations are not necessary for increased lipolysis and hepatic glycogen depletion during exercise.     

Sympatho-endocrine and metabolic responses to exercise under post-ganglionic blockade in rats

The purpose of this study was to further document the role of locally released norepinephrine (NE) in the control of metabolic and endocrine responses to exercise in rats. Post-ganglionic blockade with bretylium (20 mg.kg-1, i.v.) reduced NE release from sympathetic nerve endings and triggered a compensatory increase in epinephrine (E) release from the adrenal medulla, as reflected by plasma NE and E concentrations at rest and exercise (E/NE ratio = 2.92 +/- 0.53 and 2.48 +/- 0.51 vs 0.62 +/- 0.15 and 1.48 +/- 0.18 in control rats; mean +/- SE). Following bretylium administration a reduction in running time to exhaustion (28 m.min-1, 8% slope: 33 +/- 2 min vs 74 +/- 10 min) was associated with 1) a faster decrease in blood glucose concentration (3.58 +/- 0.80 mM vs 8.09 +/- 0.38 mM in control rats exercised for 33 min); and 2) an increased glycogen store utilization in fast-twitch muscles (superficial vastus lateralis and gastrocnemius lateralis). Glycogen utilization was not modified in soleus muscle and in the liver. Taken together these results suggest that post-ganglionic blockade increased carbohydrate store and peripheral blood glucose utilization. This could reflect an impairment in fat mobilization and utilization which might be secondary to a reduction of NE release in the adipose tissue and/or in the endocrine pancreas.     

Effect of the exercise-induced increase in glucocorticoids on endurance in the rat

To investigate the effect of the increase in glucocorticoids during exercise on endurance, rats were either sham operated (SO) or adrenalectomized. All adrenalectomized rats were given a subcutaneously implanted corticosterone pellet at the time of adrenalectomy. Adrenalectomized rats were injected with corticosterone (ADX Cort) or corn oil (ADX) 5 min before exercise. Rats were killed at rest or after running on a treadmill (21 m/min, 15% grade) until exhaustion. SO rats ran 138 +/- 6 min compared with 114 +/- 9 min for ADX Cort and 89 +/- 8 min for ADX. All differences in run times were significant (P less than 0.05). Corticosterone levels were similar in exhausted SO and ADX Cort groups. ADX exhausted rats had corticosterone levels similar to resting values in SO and ADX rats. Inhibition of the rise in glucocorticoids during exercise had no effect on liver glycogen, liver adenosine 3',5'-cyclic monophosphate, plasma insulin, blood glucose, lactate, glycerol, or 3-hydroxybutyrate, plasma norepinephrine, or red quadriceps and soleus glycogen. Plasma free fatty acids were significantly depressed at exhaustion in ADX rats compared with SO. These data show that glucocorticoids exert effects within the time frame of a prolonged exercise bout and play a role in increasing endurance.     

Neonatal chemical sympathectomy attenuates fructose-induced hypertriglyceridemia and hypertension in rats

Experiments were performed to determine the pathogenic contribution of the peripheral sympathetic nervous system to fructose-induced hypertriglyceridemia, hyperinsulinemia and hypertension in rats. Neonatal chemical sympathectomy was performed in neonatal Sprague-Dawley rats (1-week old) by administration of guanethidine (50 microg/g, i.p.) 5 times per week for consecutive 3 weeks and nerve-intact rats were served as controls. Both groups of rats were fed a fructose-enriched diet for 9 weeks. The systolic blood pressure (SBP) and body weight were measured weekly and arterial blood samples were taken weekly for determinations of plasma insulin, glucose and triglyceride levels. The results showed that fructose feeding for one week significantly increased SBP in intact rats and sympathectomized rats (116+/-1 to 119+/-1 mmHg and 116+/-1 to 120+/-1 mmHg, respectively). SBP further increased thereafter in both groups. However, the increased SBP levels were significantly higher in intact group than in sympathectomized group after 5 weeks of fructose feeding. Fructose feeding for one week concurrently produced hypertriglyceridemia that preceded the appearance of hyperinsulinemia in both groups. The elevated plasma triglyceride levels were significantly lower in sympathectomized rats than in intact rats after 3 weeks of fructose feeding, whereas the elevated plasma insulin concentrations were not different between groups throughout fructose feeding period. Plasma glucose concentrations of both groups were comparable and remained unchanged throughout the study. These data indicate that neonatal chemical sympathectomy attenuated, but did not prevent, fructose-induced elevations in blood pressure and plasma triglyceride levels, suggesting a partial dependency of fructose-induced hypertriglyceridemia and hypertension on the integrity of the peripheral sympathetic nervous system (SNS) in rats.     

Effects of selective hepatic vagotomy on running endurance in rats

The liver, through the afferent ways of the vagus hepatic nerve, may influence metabolic adaptations during exercise. This study assesses the functional significance of this hepatic innervation by determining the effect of a selective hepatic vagotomy (HV) on running endurance time during submaximal activity in rats subjected to an overnight 50% food restriction. The time to exhaustion was similar for the groups of HV and sham-operated (SHM) rats [66 +/- 15 vs. 64 +/- 21 (SD) min]. The HV group was associated with higher resting levels (P less than 0.05) of hepatic glycogen and plasma glucose. No significant differences were observed between HV and SHM rats at rest and after exercise for muscle glycogen, free fatty acids, insulin, glucagon, and lactate concentrations. These data indicate that if hepatic glucoreceptors do exist and contribute to the metabolic regulation of exercise, their functional significance is secondary to more important regulatory mechanisms.     

Sympathetic neural influences on muscle blood flow in rats during submaximal exercise

These experiments were designed to estimate the involvement of the sympathetic innervation in regulation of hindlimb muscle blood flow distribution among and within muscles during submaximal locomotory exercise in rats. Blood flows to 32 hindlimb muscles and 13 other selected tissues were measured using the radiolabeled microsphere technique, before exercise and at 0.5, 2, 5, and 15 min of treadmill exercise at 15 m/min. The two groups of rats studied were 1) intact control, and 2) acutely sympathectomized (hindlimb sympathectomy accomplished by bilateral section of the lumbar sympathetic chain and its connections to the spinal cord at L2-L3). There were no differences in total hindlimb muscle blood flow among the two groups during preexercise or at 30 s or 2 min of exercise. However, flow was higher in eight individual muscles at 2 min of exercise in the sympathectomized rats. At 5 and 15 min of exercise there was higher total hindlimb muscle blood flow in the denervated group compared with control. These differences were also present in many individual muscles. Our results suggest that 1) sympathetic nerves do not exert a net influence on the initial elevations in muscle blood flow at the beginning of exercise, 2) sympathetic nerves are involved in regulating muscle blood flow during steady-state submaximal exercise in conscious rats, and 3) these changes are seen in muscles of all fiber types.     

Effects of glucose infusion in exercising rats

To determine whether feedforward control of liver glycogenolysis during exercise is subject to negative feedback by elevated blood glucose, glucose was infused into exercising rats at a rate that elevated blood glucose greater than 10 mM. Liver glycogen content decreased 22.4 mg/g in saline-infused rats compared with 13.6 mg/g in glucose-infused rats during the first 40 min of treadmill running (21 m/min, 15% grade). Liver adenosine 3',5'-cyclic monophosphate (cAMP) concentration was significantly lower in the glucose-infused rats during the exercise bout. The concentration of hepatic fructose 2,6-bisphosphate remained elevated throughout the exercise bout in glucose-infused rats but decreased markedly in saline-infused rats. Plasma insulin concentration was higher and plasma glucagon concentration lower in glucose-infused rats than in saline-infused rats during exercise. Early in exercise, liver glycogenolysis proceeds in the glucose-infused rats despite the fact that glucose and insulin concentrations are markedly elevated and liver cAMP is unchanged from resting values. These observations suggest the existence of a cAMP-independent feedforward system for activation of liver glycogenolysis that can override classical negative feedback mechanisms during exercise.     

Effects of asphyxia at birth on postnatal glucose regulation in the rat

We have characterized the effect of a period of asphyxia at birth, followed by recovery, upon newborn rats. Asphyxiated pups were subjected to 3 to 5% (v/v) inspired oxygen during the first 20 min of life and then maintained in room air for 6 h. Control pups were maintained in room air throughout the 6-h period. Hypoxia produced severe asphyxia as reflected by a pH of 6.76 +/- 0.05, PaCO2 of 87 +/- 3 mm Hg and PaO2 of 15.4 +/- 4 mm Hg, and by a greatly increased blood lactate/pyruvate ratio. Plasma catecholamine concentrations in asphyxiated pups were elevated (epinephrine 13,866 +/- 250 pg/ml, norepinephrine 9611 +/- 1813 pg/ml) compared to control animals (epinephrine 973 +/- 234 pg/ml, norepinephrine 774 +/- 133 pg/ml) at 20 min. Asphyxia initially increased plasma glucose concentration, and then with recovery it fell below controls. Hepatic glycogen stores did not differ between asphyxiated and control pups. Plasma insulin concentrations remained elevated during asphyxia and the usual neonatal surge of plasma glucagon was significantly delayed. Neonatal asphyxia increases catecholamines, causes lactic acidemia, and alters insulin and glucagon levels. The interactions between these variables alters the normal pattern of glucose availability during the neonatal period.     

The effects of sympathectomy and dexamethasone in rats ingesting sucrose

Both high-sucrose diet and dexamethasone (D) treatment increase plasma insulin and glucose levels and induce insulin resistance. We showed in a previous work (Franco-Colin, et al. Metabolism 2000; 49:1289-1294) that combining both protocols for 7 weeks induced less body weight gain in treated rats without affecting mean daily food intake. Since such an effect may be explained by an increase in caloric expenditure, possibly due to activation of the sympathetic nervous system by sucrose ingestion, in this work, and using 10% sucrose in the drinking water, male Wistar rats were divided into 4 groups. Two groups were sympathectomized using guanethidine (Gu) treatment for 3 weeks. One of these groups of rats received D in the drinking water. Of the 2 groups not receiving Gu, one was the control (C) and the other received D. After 8 weeks a glucose tolerance test was done. The rats were sacrificed and liver triglyceride (TG), perifemoral muscle lipid, and norepinephrine (NE) levels in the liver spleen, pancreas, and heart were determined. Gu-treated rats (Gu and Gu+D groups) showed less than 10% NE concentration compared to C and D rats, less daily caloric intake and body-weight gain, more sucrose intake, and better glucose tolerance. The area under the curve after glucose administration correlated significantly with the mean body weight gain of the rats, except for D group. Groups D (D and Gu+D) also showed less caloric intake and body-weight gain but higher liver weight and TG concentration and lower peripheral muscle mass. The combination of Gu+D treatments showed some peculiar results: negative body weight gain, a fatty liver, and low muscle mass. Though the glucose tolerance test had the worst results for the D group, it showed the best results in the Gu+D group. There were significant interactions for Guan X Dex by two-way ANOVA test for the area under the curve in the glucose tolerance test, muscle mass, and muscle lipids. The results suggest that dexamethasone catabolic effect is not caused by sympathetic activation.     

Effect of moderate incremental exercise, performed in fed and fasted state on cardio-respiratory variables and leptin and ghrelin concentrations in young healthy men.

BACKGROUND: Although hormonal responses to exercise performed in fed state are well documented, far less in known about the effect of a single exercise bout, performed after overnight fasting, on cardio-respiratory responses and hormones secretion. It has been reported that recently discovered hormones as leptin and ghrelin may affect cardiovascular responses at rest. However, their effect on the cardiovascular responses to exercise is unknown. AIMS: This study was designed to determine the effect of overnight fasting on cardio- respiratory responses during moderate incremental exercise. We have hypothesised that fasting / exercise induced changes in plasma leptin / ghrelin concentrations may influence cardiovascular response. MATERIAL AND METHODS: Eight healthy non-smoking men (means +/- SE.: age 23.0 +/- 0.5 years; body mass 71.9 +/- 1.5 kg; height 179.1 +/- 0.8 cm; BMI 22.42 +/- 0.49 kg x m(-2) with VO2max of 3.71 +/- 0.10 l x min(-1)) volunteered for this study. The subjects performed twice an incremental exercise test, with the increase of power output by 30 W every 3 minutes. Tests were performed in a random order: once in the feed state--cycling until exhaustion and second, about one week later, after overnight fasting--cycling until reaching 150 W. RESULTS: In the present study we have compared the results obtained during incremental exercise performed only up to 150 W (59 +/- 2 % of VO2max) both in fed and fasted state. Heart rate measured during exercise at each power output, performed in fasted state was by about 10 bt x min(-1) (p = 0.02) lower then in fed subjects. Respiratory quotient and plasma lactate concentration in fasted state were also significantly (p<0.001) lower than in the fed state. Pre-exercise plasma leptin and ghrelin concentrations were not significantly different in fed and fasted state. Exercise induced increase in hGH was not accompanied by a significant changes in the studied gut hormones such as ghrelin, leptin, and insulin, except for plasma gastrin concentration, which was significantly (p = 0.008) lower in fasting subjects at the power output of 150 W. Plasma [IL-6] at rest before exercise performed in fasted state was significantly (p = 0.03) elevated in relation to the fed state. This was accompanied by significantly higher (p = 0.047) plasma noradrenaline concentration. Plasma IL-6 concentration at rest in fed subjects was negatively correlated with plasma ghrelin concentration (r = -0.73, p < 0.05) and positively correlated with plasma insulin concentration (r = 0.78, p < 0.05). Significant negative correlation (r = -0.90; p < 0.05) was found between plasma insulin and ghrelin concentration at rest in fed subjects. CONCLUSIONS: We have concluded that plasma leptin and ghrelin concentrations have no significant effect on the fasting-induced attenuation of heart rate during exercise. We have postulated that this effect is caused by increased plasma norepinephrine concentration, leading to the increase in systemic vascular resistance and baroreceptor mediated vagal stimulation. Moreover we believe, that the fasting-induced significant increase in plasma IL-6 concentration at rest, accompanied by higher plasma norepinephrine concentration and lower RQ, belongs to the physiological responses, maintaining energy homeostasis in the fasting state.     

Glucose feedings and exercise in rats: glycogen use, hormone responses, and performance

This study compared the effects of glucose feeding and water on endurance performance, glycogen utilization, and endocrine responses to exhaustive running in rats. Forty-eight trained rats ran at approximately 70% peak O2 consumption (VO2) while receiving, via gavage, 1 ml of an 18% glucose solution or water every 30 min. Glucose- (GF) and water-fed rats (WF) were pair matched and killed at rest, at 25 or 50% of their previously determined run time to exhaustion, or at exhaustion. Run times to exhaustion were 4.6 +/- 1.0 and 3.0 +/- 0.9 h in GF and WF rats, respectively. In WF rats, plasma glucose declined continuously from a resting value of 7.4 +/- 0.5 to 1.8 +/- 0.5 mM at exhaustion and was lower than in GF rats at all exercise time points. In GF rats, glucose was maintained at 7.4 +/- 0.5 mM for 3 h before dropping to 3.9 +/- 0.6 mM at exhaustion. In both groups, liver and muscle glycogen decreased dramatically during the 1st h and changed only slightly thereafter. During the 3rd h, glycogen levels were maintained in GF rats but continued to decrease in WF rats (P less than 0.05). Insulin decreased during exercise and was not significantly different between groups. Glucagon, epinephrine, norepinephrine, and corticosterone increased to a greater extent in WF than in GF rats during the first 3 h of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise

The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177 +/- 144 muEq/l, m +/- SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization.     

Effect of bombesin upon plasma somatostatin-like immunoreactivity, insulin and glucagon in normal and chemically sympathectomized dogs

The present study was designed to determine the effects of intravenously infused bombesin (10 ng/kg/min) upon basal and postprandial plasma somatostatin-like immunoreactivity (SLI), glucagon, insulin and triglyceride levels in normal (n = 12) and chemically sympathectomized (n = 11) dogs. Basal plasma SLI, glucagon and insulin levels rose significantly during the infusion of bombesin in the normal dogs, and this was not altered by chemical sympathectomy. Bombesin infusion enhanced the postprandial SLI response, while attenuating the postprandial glucagon response by 50% and the insulin response in the early postprandial phase of the meal. Sympathectomy did not significantly alter the basal levels of these polypeptides, but augmented the postprandial plasma SLI response during the first 90 min, and reduced the postprandial glucagon response during the infusion of bombesin. The postprandial insulin response was not affected by sympathectomy. In both normal and chemically sympathectomized dogs the rise in postprandial triglyceride levels was attenuated by bombesin infusion.     

Metabolic and endocrine responses to graded exercise under acute hypoxia

Eight male subjects (24 +/- 1 years old) performed graded ergocycle exercises in normoxic (N) and acute hypoxic (H) conditions (14.5% O2). VO2max decreased from 55.5 +/- 1.3 to 45.8 +/- 1.4 ml . kg-1 . min-1 in H condition. Plasma glucose and free fatty acid concentrations remained unchanged throughout exercise in both conditions. Increase in blood lactate concentration was associated with relative workload in both conditions. At VO2max lactate concentrations were similar in the two conditions, plasma insulin, glucagon, and LH concentrations did not significantly change in either. Plasma delta 4-androstenedione and testosterone increased in a similar manner in both conditions. Finally plasma norepinephrine concentration reached at VO2max was significantly lower in hypoxia. These results suggest that acute moderate hypoxia does not affect metabolic and hormonal responses to short exercise performed at similar relative workloads, i.e. when the reduction of VO2max due to hypoxia is taken into consideration. The lower catecholamine response to maximal exercise under acute hypoxia might suggest that the sympathetic response could be related to relative as well as absolute workloads.     

Central adrenergic suppression augments the insulin and glucagon secretory, and the glycogenolytic responses in streptozotocin-diabetic rats.

It has been suggested that the increased activity of the sympathetic nervous system and the resultant increase in the tissue catecholamine levels contribute to the pathogenesis of diabetes. In this study we evaluated the effect of clonidine, a central adrenergic agonist that decreases sympathetic tone, on the serum levels of glucose, insulin, glucagon and norepinephrine and on the hepatic glycogen content in normal and streptozotocin-diabetic rats. The animals were treated with clonidine 25 micrograms/kg/day interperitoneally for 3 weeks to suppress the central adrenergic impulses. Clonidine treatment significantly increased the weight gain, but did not affect plasma glucose, insulin, glucagon and norepinephrine in the diabetic animals. Pancreatic insulin and liver glycogen contents were significantly higher in the clonidine-treated than in the untreated diabetic rats. However, clonidine did not affect pancreatic insulin and liver glycogen content of nondiabetic animals. The intravenous administration of glucagon increased plasma glucose in the clonidine-treated, but not in the saline-treated diabetic rats. Insulin-induced hypoglycemia significantly enhanced glucagon release in clonidine-treated but not in saline-treated diabetic rats. We conclude that the suppression of central adrenergic activity may ameliorate the effects of insulin insufficiency on pancreatic hormone secretion and hepatic glycogen content.     

Effect of maternal exercise on fetal liver glycogen late in gestation in the rat

To determine the effect of maternal exercise on fetal liver glycogen content, fed and fasted rats that were pregnant for 20.5 or 21.5 days were run on a rodent treadmill for 60 min at 12 m/min with a 0% grade or 16 m/min up a 10% grade. The rats were anesthetized by intravenous injection of pentobarbital sodium, and fetal and maternal liver and plasma samples were collected and frozen. Fetal liver glycogenolysis did not occur as a result of maternal exercise. Fetal blood levels of lactate increased 22-60%, but glucose, plasma glucagon, and insulin were unchanged during maternal exercise. Maternal liver glycogen decreased as a result of exercise in all groups of rats except the fasted 20.5-day-pregnant group. Plasma free fatty acids increased in all groups and blood lactate increased in fed (20.5 days) and fasted (21.5 days) pregnant rats. Maternal glucose, glucagon, and insulin values remained constant during exercise. The fetus appears to be well-protected from metabolic stress during moderate-intensity maternal exercise.     

Subsensitivity to insulin in adipocytes from rats submitted to foot-shock stress

We examined the effect of three daily foot-shock stress sessions on glucose homeostasis, insulin secretion by isolated pancreatic islets, insulin sensitivity of white adipocytes, and glycogen stores in the liver and soleus muscle of rats. Stressed rats had plasma glucose (128.3 +/- 22.9 mg/dL) and insulin (1.09 +/- 0.33 ng/mL) levels higher than the controls (glucose, 73.8 +/- 3.5 mg/dL; insulin, 0.53 +/- 0.11 ng/mL, ANOVA plus Fisher's test; p < 0.05). After a glucose overload, the plasma glucose, but not insulin, levels remained higher (area under the curve 8.19 +/- 1.03 vs. 4.84 +/- 1.33 g/dL 30 min and 102.7 +/- 12.2 vs. 93.2 +/- 16.1 ng/mL 30 min, respectively). Although, the area under the insulin curve was higher in stressed (72.8 +/- 9.8 ng/mL) rats than in control rats (34.9 +/- 6.9 ng/mL) in the initial 10 min after glucose overload. The insulin release stimulated by glucose in pancreatic islets was not modified after stress. Adipocytes basal lipolysis was higher (stressed, 1.03 +/- 0.14; control, 0.69 +/- 0.11 micromol of glycerol in 60 min/100 mg of total lipids) but maximal lipolysis stimulated by norepinephrine was not different (stressed, 1.82 +/- 0.35; control, 1.46 +/- 0.09 micromol of glycerol in 60 min/100 mg of total lipids) after stress. Insulin dose-dependently inhibited the lipolytic response to norepinephrine by up to 35% in adipocytes from control rats but had no effect on adipocytes from stressed rats. The liver glycogen content was unaltered by stress, but was lower in soleus muscle from stressed rats than in control rats (0.45 +/- 0.04 vs. 0.35 +/- 0.04 mg/100 mg of wet tissue). These results suggest that rats submitted to foot-shock stress develop hyperglycemia along with hyperinsulinemia as a consequence of insulin subsensitivity in adipose tissue, with no alteration in the pancreatic sensitivity to glucose. Foot-shock stress may therefore provide a useful short-term model of insulin subsensitivity.     

Insulin and glucagon response during hemorrhage induced hyperglycemia

Rapid hemorrhage to 50 mmHg (1 mmHg = 133.322 Pa) in the pentobarbital-anesthetized cat leads to severe hyperglycemia which declines only slightly by 90 min of hemorrhage. Insulin levels decline to less than one-half of control levels and remain low throughout, despite the hyperglycemia. Glucagon levels decline at 15 min but are significantly elevated by 90 min. These data confirm that the hepatic glycogenolysis is controlled almost entirely by hepatic sympathetic nerves and adrenal secretions with no role for elevated glucagon levels at the early stages in hemorrhage. Hepatic denervation leads to lesser insulin suppression and greater glucagon elevation at later times (45 and 90 min), suggesting that intact hepatic nerves are required for a normal pancreatic response. Hepatic sympathectomy did not produce these effects. Insulin responses remained normal, but glucagon levels were suppressed throughout the entire experiment in sympathectomized cats. The data suggest that hepatic nerves may modulate insulin and glucagon levels during hemorrhage in an unknown manner.     

Interactions between oxytocin, glucagon and glucose in normal and streptozotocin-induced diabetic rats

Oxytocin has been suggested to have glucoregulatory functions in rats, man and other mammals. The hyperglycemic actions of oxytocin are believed to be mediated indirectly through changes in pancreatic function. The present study examined the interaction between glucose and oxytocin in normal and streptozotocin (STZ)-induced diabetic rats, under basal conditions and after injections of oxytocin. Plasma glucose and endogenous oxytocin levels were significantly correlated in cannulated lactating rats (r = 0.44, P less than 0.01). To test the hypothesis that oxytocin was acting to elevate plasma glucose, adult male rats were injected with 10 micrograms/kg oxytocin and killed 60 min later. Oxytocin increased plasma glucose from 6.1 +/- 0.1 to 6.8 +/- 0.2 mM (P less than 0.05), and glucagon from 179 +/- 12 to 259 +/- 32 pg/ml (P less than 0.01, n = 18). There was no significant effect of oxytocin on plasma insulin, although the levels were increased by 30%. A lower dose (1 microgram/kg) of oxytocin had no significant effect on plasma glucose or glucagon. To eliminate putative local inhibitory effects of insulin on glucagon secretion, male rats were made diabetic by i.p. injection of 100 mg/kg STZ, which increased glucose to greater than 18 mM and glucagon to 249 +/- 25 pg/ml (P less than 0.05). In these rats, 10 micrograms/kg oxytocin failed to further increase plasma glucose, but caused a much greater increase in glucagon (to 828 +/- 248 pg/ml) and also increased plasma ACTH. A specific oxytocin analog, Thr4,Gly7-oxytocin, mimicked the effect of oxytocin on glucagon secretion in diabetic rats. The lower dose of oxytocin also increased glucagon levels (to 1300 +/- 250 pg/ml), but the effect was not significant. A 3 h i.v. infusion of 1 nmol/kg per h oxytocin in conscious male rats significantly increased glucagon levels by 30 min in normal and STZ-rats; levels returned to baseline by 30 min after stopping the infusion. Plasma glucose increased in the normal, but not STZ-rats. The relative magnitude of the increase in glucagon was identical for normal and diabetic rats, but the absolute levels of glucagon during the infusion were twice as high in the diabetics. To test whether hypoglycemia could elevate plasma levels of oxytocin, male rats were injected i.p. with insulin and killed from 15-180 min later. Plasma glucose levels dropped to less than 2.5 mM by 15 min. Oxytocin levels increased by 150-200% at 30 min; however, the effect was not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)