Effects of oxytocin delivery on counter-regulatory hormone response in insulin-dependent (type 1) diabetic subjects

In insulin-dependent (type 1) diabetic subjects (n = 7) with intact hormone response to hypoglycaemia, oxytocin infusion (0.2 mU/min over 60 min) produced significant rises in basal plasma glucagon and adrenaline levels, while it reduced basal plasma cortisol levels. During insulin-induced hypoglycaemia, oxytocin potentiated the increases in plasma glucagon and adrenaline, while an inhibitory effect on plasma cortisol levels was still present. In insulin-dependent (type 1) diabetic subjects (n = 7) with blunted counter-regulatory hormone response to hypoglycaemia, the same dose of oxytocin (0.2 mU/min over 60 min) increased basal plasma glucose and glucagon concentrations and lowered basal plasma cortisol concentration. In the same group of patients, oxytocin delivery (0.2 mU/min), simultaneously to an insulin-induced hypoglycaemia, produced a significant elevation of plasma glucagon and adrenaline concentrations thus enhancing glucose recovery from hypoglycaemia. In conclusion, in insulin-dependent (type 1) diabetic patients, oxytocin delivery enhances plasma glucagon and adrenaline levels in basal conditions and during insulin-induced hypoglycaemia.     

Effect of pinealectomy on plasma glucose, insulin and glucagon levels in the rat

In an attempt to know the role of the pineal gland on glucose homeostasis, the blood plasma concentrations of glucose, insulin and glucagon under basal conditions or after the administration of nutrients were studied in the jugular vein of conscious pinealectomized (Pn), melatonin-treated pinealectomized (Pn + Mel) and control (C) rats. Glucose levels were smaller in C than in Pn rats, while immunoreactive insulin (IRI) concentrations were significantly greater in C than in Pn rats. Contrary to this, immunoreactive glucagon (IRG) levels were significantly greater in Pn than in C animals. Melatonin treatment of Pn rats induces an increase of IRI concentrations and a reduction in IRG levels. Similar changes were obtained when hormonal determinations were carried out in portal blood plasma. Although ether anesthesia increases circulating glucagon levels in the porta and cava veins, the qualitative changes of plasma insulin and glucagon in Pn and Pn + Mel were similar to those found in conscious rats. To determine the effects of nutrients on pancreatic hormone release, intravenous arginine or oral glucose were administered to the animals of the three experimental groups. In C rats, both glucose and IRI levels reached a peak 30 minutes after glucose ingestion, decreasing thereafter. However, in Pn rats a glucose intolerance was observed, with maximum glucose and insulin concentrations at 60 minutes, while in Pn + Mel animals, glucose and IRI concentrations were in between the data obtained with the other two groups. Furthermore, glucose ingestion induced a significant reduction of IRG levels in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ghrelin injection on plasma concentrations of glucose, pancreatic hormones and cortisol in Holstein dairy cattle

Ghrelin affects not only growth hormone secretion but also nutrient utilization and metabolic hormone secretion in humans and experimental animals. The effects of ghrelin on plasma metabolic hormone and metabolite levels in domestic herbivores remain unclear despite the fact that the physiological characteristics of nutrient digestion and absorption imply specific responses to ghrelin. Therefore, the effects of ghrelin on plasma glucose, pancreatic hormones and cortisol concentrations were investigated in Holstein dairy cattle in various physiological states. Ghrelin (0.3 nmol/kg) or placebo (2% bovine serum albumin in saline) was intravenously injected in pre-ruminant calves (pre-rumen function), adult non-lactating (functional rumen) and lactating cows (functional rumen and lactation), and plasma glucose, insulin, glucagon and cortisol concentrations were then determined. Ghrelin injection increased plasma glucose concentrations in adult cows, especially in lactating cows. No hyperglycemic response was observed in pre-ruminant calves. A transient rise of insulin and glucagon levels was distinctively found in lactating cows in response to the ghrelin administration. Ghrelin injection decreased the insulin level in pre-ruminant calves. Ghrelin increased cortisol secretion independently of the physiological state. The results of the present study suggest that the effects of ghrelin on plasma glucose and pancreatic hormone levels may reflect differences in the physiological states of dairy cattle.     

Hypoinsulinemic and hyperglycemic effects of beta-endorphin in rabbits

The present study was designed to investigate the in vivo effects of beta-endorphin on plasma levels of glucagon, insulin and glucose in rabbits, and to elucidate some of the mechanisms involved. beta-Endorphin (50 micrograms) injected intravenously into fasted rabbits, decreased plasma levels of insulin (-4.5 +/- 1.3 microU/ml, P less than 0.05) and increased plasma levels of glucose (+2.7 +/- 0.4 mmol/l, P less than 0.05). Similar hypoinsulinemic and hyperglycemic effects were observed for 25 and 2.5 micrograms beta-endorphin in fasted and 50 and 0.5 micrograms beta-endorphin in fed rabbits. beta-Endorphin produced slight and transient increases in plasma levels of glucagon at the highest dose in fed rabbits, only (+80 +/- 9 pg/ml, P less than 0.05). The beta-endorphin-induced hypoinsulinemia was not inhibited by phentolamine, yohimbine, propranolol or atropine, which is in consistency with a direct inhibitory effect of beta-endorphin on the beta-cell in rabbits. The beta-endorphin-induced hyperglycemia was reduced by naloxone (+0.8 +/- 0.1 mmol/l) but not by N-methyl-naloxone (ORG 10908) a peripheral opiate receptor blocking drug (+2.2 +/- 0.2 mmol/l), suggesting a central nervous action on opiate receptors. This central action of beta-endorphin was probably not mediated by catecholamine release or other stimulation of adrenergic or muscarinic receptors, since the beta-endorphin-induced hyperglycemia was not inhibited by phentolamine, yohimbine, propranolol or atropine. These results suggest that the beta-endorphin-induced hyperglycemia was caused, at least in part, by a peripheral inhibition of insulin release and a central stimulation on glucoregulation.     

Increase of beta-endorphin serum levels by human corticotropin-releasing factor does not affect beta-cell function in normal-weight men

Numerous studies have shown a rise of blood sugar concentrations and serum levels of pancreatic polypeptides after pharmacological doses of beta-endorphin. We tested the yet unknown influence of physiological fluctuations in beta-endorphin serum levels on glucose homeostasis by stimulating the pituitary secretion with CRF. 100 micrograms of human CRF or saline solution were intravenously injected in ten healthy male subjects at least one week apart. beta-endorphin serum levels rose significantly after the injection of CRF, but there was no change in blood sugar concentrations or serum levels of glucagon or insulin at all. We conclude that only a pharmacological dose of beta-endorphin influences glucose homeostasis.     

Response of plasma endorphins, prolactin and catecholamines in women to intense heat in a sauna

Concentrations of immunoreactive beta-endorphin (ir beta-E), corticotropin, cortisol, prolactin and catecholamines in plasma were followed in 11 healthy women during and after exposure to intense heat in a Finnish sauna bath, and compared to those in a similar control situation without exposure to heat. Heat stress significantly increased prolactin and norepinephrine secretion; the percentage increases from the initial plasma concentrations varied from 113 to 1280% (mean 510%) and from 18 to 150% (mean 86%), respectively. The response of the plasma levels of epinephrine, ir beta-E, corticotropin and cortisol to heat exposure was variable. Compared to the control situation, no statistically significant effect of heat exposure on the plasma levels of these hormones was found.     

Fetal and maternal endocrine responses to exercise in the pregnant ewe

Maternal and fetal concentrations of plasma insulin, pancreatic glucagon, growth hormone (GH), corticosteroids and enteroglucagon, and of blood glucose and lactate, were measured in well-fed, late pregnant ewes before, during and after walking on a treadmill at 0.7 m.s-1, 10 degrees slope for 60 min. Exercise caused rapid and substantial increases in maternal concentrations of glucose, lactate, pancreatic glucagon and corticosteroids, smaller but significant decreases in levels of GH and enteroglucagon, and no change in insulin. With the exception of GH, concentrations of these maternal hormones had returned to pre-exercise levels within 20 min of stopping exercise. The exercise-induced maternal hyperglycaemia was associated with a proportionately similar, rapid increase in fetal blood glucose; fetal blood lactate and plasma corticosteroids also increased, but at slower rates and other fetal hormone concentrations were unchanged. During recovery there was a rapid increase in fetal insulin levels. The results are discussed in terms of the regulation of exercise-induced changes in maternal energy metabolism, and fetal metabolic and hormonal sensitivity to these changes.     

Stimulation of gastric glucagon secretion by epinephrine administration in dogs

To determine the response of gastric A-cells to adrenergic substances, immunoreactive glucagon was determined simultaneously in the jugular vein and in the left gastroepiploic vein of totally depancreatized dogs. Under basal conditions a significant gradient of glucagon concentrations between the jugular and gastric veins was observed, whereas plasma insulin values were almost undetectable. Intravenous administration of epinephrine elicits a prompt and significant increase in glucagon concentrations in the gastric vein which persist during the time of hormone infusion. To ensure adequate adrenergic blockade, blockers were infused before epinephrine administration. Accordingly, after phentolamine, the infusion of epinephrine failed to increase gastric glucagon concentrations, while after propranolol, epinephrine induced a significant release of gastric glucagon. These results indicate that epinephrine stimulates gastric glucagon secretion and that this effect is mediated through alpha-adrenergic receptors.     

Effects of ovine corticotropin-releasing factor and vasopressin on plasma beta-endorphin, cortisol and behavior after minor surgery in sheep

The evidence for an analgesic effect arising from increased peripheral concentrations of beta-endorphin (beta-EP) in various animal species is controversial, and has not been fully evaluated in the sheep. To stimulate beta-EP release, ovine corticotropin-releasing factor (oCRF) and arginine vasopressin (AVP) were injected intravenously (iv) into a group of 12 out of 24 sheep, 15 min prior to minor surgery on all sheep. This brought about significant increases (P less than 0.01) in plasma beta-endorphin (beta-EP) and cortisol concentrations, relative to the non-injected control sheep, 15-30 min after injection. Ultrafiltration indicated that less than 30% of the released beta-EP immunoreactivity was present as higher molecular weight forms (mol. wt greater than 10,000) and that the majority (about 75%) of the beta-EP was probably bound to plasma proteins. By 75 min after injection there was no significant difference in plasma beta-EP or cortisol concentrations between the two groups of sheep. Consistent with previous observations the sheep showed a characteristic aversive behavior to the human handler following surgery, lasting several days. This behavior appeared to be unaffected by a pre-operative increase in peripheral plasma beta-EP, and may indicate that this increase in beta-EP was not sufficiently analgesic to block the cognitive response to the operation, or long-lasting enough to prevent the perception of post-operative soreness.     

Effects of adrenocorticotropin stimulation on cortisol dynamics of pregnant gilts and their fetuses: implications for prenatal stress studies

The effect of adrenocorticotropic hormone (ACTH) administration on plasma cortisol concentrations was determined in pregnant gilts and their fetuses. In a first experiment, 100 IU ACTH (Synacthen Depot) was administered intramuscularly to the gilts every second day from Days 49 to 75 of gestation. ACTH injections were carried out at 08:00 h and, thereafter, 10 blood samples were taken within the following 8h via jugular catheters. Blood samples were analysed for plasma cortisol concentrations, and results were compared with values from animals which were treated with physiological saline and untreated animals (blood sampling only). The values for plasma cortisol concentrations increased until 3h after ACTH applications to a mean maximum level of 276.5+/-17.2 nmol/l in the whole 4-week stimulation period. Plasma cortisol levels did not return to pre-treatment values within the 8 h post-injection. No differences in cortisol levels were found between the physiological saline and untreated control, and no habituation of the adrenocortical response to ACTH was found during the 4-week stimulation period. In a second experiment, 100 IU ACTH were administered to pregnant gilts at gestation Day 65. After 3 h, fetuses were recovered under general anaesthesia and blood samples were taken from the umbilical vein, artery, and, after decapitation, from periphery. Application of ACTH to the sows significantly increased their plasma cortisol concentrations (P<0.001), and also increased plasma cortisol concentrations in peripheral blood samples from the fetuses (P=0.09) and in the umbilical vein (P<0.001) and artery (P<0.01), respectively. Plasma ACTH concentrations did not differ in fetuses from ACTH-treated or control sows. The results show that in gilts the adrenocortical response to an exogenous application of Synacthen Depot is consistent over time during mid-gestation. Furthermore, cortisol but not ACTH levels were increased in fetuses from ACTH-treated sows, indicating that maternal cortisol can cross the placenta during mid-gestation. The stimulation of maternal cortisol release through exogenous ACTH with subsequent elevation of fetal cortisol levels is, therefore, a useful approach for studying effects of elevated maternal glucocorticoids in prenatal stress studies in pigs.     

Changes in selected blood component concentrations of rainbow trout, Salmo gairdneri Richardson, exposed to hypoxia or sublethal concentrations of phenol or ammonia

Rainbow trout were exposed to sublethal phenol or non-ionized ammonia concentrations or to hypoxia. Blood samples were taken after various exposure periods and the packed cell volume (PCV) value, the whole blood glucose concentration and the plasma cortisol and chloride ion concentrations measured. At low pollutant concentrations there were no significant changes in the blood components compared to control fish values. At higher concentrations the general response to the stressors was significant increases in the PCV value and the glucose and cortisol concentrations during the first few hours of exposure, followed by a gradual return to normal values in the subsequent exposure time. The increases in glucose and cortisol concentrations were approximately proportional to the pollutant concentrations no such correlation was found for the PCV values. No clear pattern of plasma chloride ion changes was found in any experiment. Levels of no acute effect, in terms of toxic units (TU) based on the pollutants' 48 h LC₅₀ values, were estimated for phenol as 0.3 TU and for un-ionized ammonia as 0.1 TU, using the plasma cortisol concentration measurements. The use of fish blood component measurements as general indicators of a stress response is discussed.     

Assessment of plasma opioid peptides, beta-endorphin and met-enkephalin, at the end of an international nordic ski race

Plasma met-enkephalin, beta-endorphin, cortisol and lactic acid concentrations were measured in seventeen volunteer male subjects at rest and after a long-distance nordic ski race. Immediately after the race, mean plasma met-enkephalin did not show any significant change, but significant rises in beta-endorphin, cortisol and lactic acid were noted in all skiers. The change in beta-endorphin with exercise was significantly related to the change in cortisol (r = 0.68; p less than 0.001) and to the change in plasma lactic acid (r = 0.60; p less than 0.001). Furthermore, the experienced skiers training over 150 km X week-1 of nordic ski had significantly faster skiing times in this event and showed greater beta-endorphin, cortisol and lactic acid levels than the recreational skiers who trained for 20 km X week-1. Our results imply that the changes in plasma beta-endorphin depend on the intensity of exercise. However the significance of higher levels of skiing training or previous nordic ski experience in the release of beta-endorphin is expected and cannot be excluded.     

Circadian studies of plasma cortisol, thyroid hormone, protein, glucose and ion concentration, liver glycogen concentration and liver and spleen weight in rainbow trout, Salmo gairdneri Richardson

1. Although there are many reports in the literature of circadian rhythms in plasma hormone and metabolite levels, the data are highly variable between research groups. The present study attempts to re-examine whether circadian rhythm in plasma cortisol, thyroid hormone, ions, glucose and protein levels and liver glycogen levels are evident in rainbow trout, Salmo gairdneri, and determine whether there is a significant correlation between any of the measured variables. 2. Significant fluctuations throughout the day were found in all measured variables; although these fluctuations appear to be a normal component in the homeostatic function of rainbow trout, their timing was neither consistent nor predictable. 3. "Circadian-like" patterns were observed in levels of plasma cortisol, glucose, Mg2+ and K+ concentrations and liver glycogen concentration. 4. Seasonal variations in these circadian-like rhythms were found in liver glycogen and plasma cortisol, Mg2+ and K+ concentrations. 5. Plasma cortisol and glucose concentrations were affected by time of feeding. 6. There were significant correlations between plasma thyroid hormone and plasma protein levels, but no other significant correlation between any of the measured variables was found.     

Effect of somatostatin in the Syrian hamster bearing a transplantable islet-cell tumor.

The influence of somatostatin (SRIF) on blood glucose, plasma insulin and plasma glucagon was studied in hamsters bearing a transplantable islet-cell tumor secreting insulin and glucagon as well as in normal controls. Fed anesthetized animals were infused intraperitoneally either at a dose of 10 microgram in 15 min or of 150 microgram in 30 min, and intravenously at a dose of 250 microgram in 30 min. Blood was withdrawn from the jugular vein before and after infusion. Before the infusions, tumor bearing animals (TB) had lower blood glucose, markedly elevated plasma glucagon and slightly lower plasma insulin by comparison with normal hamsters (N). Both doses of somatostatin infused by the intraperitoneal route produced a slight but significant hypoglycemia in TB hamsters but not in normals. Ten microgram SRIF did not affect insulin and plasma glucagon levels whereas 150 microgram SRIF significantly depressed plasma insulin in both types of hamsters (N and TB). This latter dose of SRIF decreased plasma glucagon in normal but not in tumor-bearing hamsters. Intravenous infusion of 250 microgram SRIF did not reduce the hyperglucagonemia of TB hamsters either. These results indicate that somatostatin does not reduce the hyperglucagonemia due to the transplantable islet-cell tumor but nevertheless decreases blood glucose and plasma insulin.     

Indomethacin does not affect endogenous glucose production in type 2 diabetes mellitus.

In healthy subjects, basal endogenous glucose production is partly regulated by paracrine intrahepatic factors. It is currently unknown whether paracrine intrahepatic factors also influence the increased basal endogenous glucose production in patients with type 2 diabetes mellitus. Administration of indomethacin to patients with type 2 diabetes mellitus stimulates endogenous glucose production and inhibits insulin secretion. Our aim was to evaluate whether this stimulatory effect on glucose production is solely attributable to inhibition of insulin secretion. In order to do this, we administered indomethacin to 5 patients with type 2 diabetes during continuous infusion of somatostatin to block endogenous insulin and glucagon secretion and infusion of basal concentrations of insulin and glucagon in a placebo-controlled study. Endogenous glucose production was measured 3 hours after the start of the somatostatin, insulin and glucagon infusion, for 4 hours after administration of placebo/indomethacin, by primed, continuous infusion of [6,6-(2)H(2)] glucose. At the time of administration of placebo or indomethacin, there were no significant differences in plasma glucose concentrations and endogenous glucose production rates between the two experiments (16.4 +/- 2.09 mmol/l vs. 16.6 +/- 1.34 mmol/l and 17.7 +/- 1.05 micromol/kg/min and 17.0 +/- 1.06 micromol/kg/min), control vs. indomethacin). Plasma glucose concentration did not change significantly in the four hours after indomethacin or placebo administration. Endogenous glucose production in both experiments was similar after both placebo and indomethacin. Mean plasma C-peptide concentrations were all below the detection limit of the assay, reflecting adequate suppression of endogenous insulin secretion by somatostatin. There were no differences in plasma concentrations of insulin (76 +/- 5 vs. 74 +/- 4 pmol/l) and glucagon (69 +/- 8 vs. 71 +/- 6 ng/l) between the studies with levels remaining unchanged in both experiments. Plasma concentrations of cortisol, epinephrine, and norepinephrine were similar in the two studies and did not change significantly. We conclude that indomethacin stimulates endogenous glucose production in patients with type 2 diabetes mellitus by inhibition of insulin secretion.     

Increments in glucose, glucagon and insulin after morphine in rats, and naloxone blocking of this effect.

In awake rats adapted to experimental conditions and allowed food ad libitum, hyperglycemia was induced by the administration of morphine 10 mg/kg through indwelling catheters in the external jugular vein. High glucose values were measured at 5, 15 and 25 min. Glucagon values were high at 5 and 15 min, and again at basal level at 25 min. Insulin was increased after morphine both at 5, 15 and 25 min, whereas somatostatin levels did not change after morphine. When morphine was administered together with naloxone after an initial 10 min period of naloxone administration, there was no increment in glucose, insulin or somatostatin values; neither at 5, 15 or 25 min. There was a remarkable glucagon decrease after naloxone and morphine remaining from 5 to 25 min. Then, one of the possible mechanisms for the hyperglycemic response after morphine may be an opioid effect on pancreas, stimulating glucagon and thereby causing hepatic glucose output.     

In vivo and in vitro effects of beta-endorphin on glucose metabolism in the rat

The effects of beta-endorphin (beta-Ep) on plasma glucose levels in rats and on glucose metabolism in isolated rat liver cells were examined. Intravenous injection of beta-Ep (5 micrograms/100 g BW) into ether-anaesthetized rats resulted in prompt and sustained hyperglycaemia with increases in the plasma glucagon and somatostatin levels and decrease in the plasma insulin level. When liver cells isolated from fed rats were incubated in the presence of beta-Ep at concentrations of 6 X 10(-8) M to 6 X 10(-7) M, glucose release into the medium increased within 15 min in a dose-related manner. Time course experiments showed that beta-Ep increased the level of cyclic AMP within 3 min. Significant increase in gluconeogenesis in liver cells isolated from fasted rats was also observed on addition of 10(-7) M beta-Ep in the presence of 10 mM L-lactate. These results suggest that the hyperglycaemia induced by beta-Ep may be caused, at least in part, by the effects of beta-Ep on releases of pancreatic hormones and glucose production in liver cells.     

Endocrine and metabolic responses to stress in a laboratory population of the tropical damselfish Acanthochromis polyacanthus

The effects of confinement and exercise on the stress response of the spiny damselfish Acanthochromis polyacanthus were investigated in a laboratory stock of fish. Cultured spiny damselfish had basal plasma cortisol values (<16 ng ml⁻¹) similar to those found in wild fish, and basal plasma glucose and lactate levels that were similar to those found in other teleosts. Plasma cortisol concentrations increased in response to stress with a latency period of 5–10 min. Removal of the stressor resulted in partial recovery of cortisol levels by 24 h. Plasma glucose levels increased in response to stress in all experiments with significant increases occurring within 15 min of the imposition of stress. Elevations in plasma glucose concentrations were not initially reflected in changes in liver or muscle glycogen content, with significant reductions in liver glycogen concentrations only occurring in response to extended periods of stress. In contrast to many temperate species, plasma lactate concentrations did not consistently increase in response to stress, suggesting that the stress response in spiny damselfish is not strongly characterized by anaerobiosis.     

Bromocriptine is unable to suppress TRH-stimulated beta-endorphin/beta-lipotropin and cortisol secretion in normal pregnant women after delivery

The course of plasma beta-endorphin/beta-lipotropin, cortisol and prolactin (PRL) levels was followed from 0.5 till 5 h after normal delivery in 13 healthy women. Six subjects who did not want to breast-feed their child received 2.5 mg bromocriptine orally 1 h after delivery. After 3 h the effect of the intravenous administration of 200 micrograms thyrotropin-releasing hormone (TRH) was also measured. Elevated plasma beta-endorphin and cortisol levels decreased after delivery in a (log) linear fashion which was not influenced by bromocriptine. TRH elicited a significant short-lived identical increase in plasma beta-endorphin/beta-lipotropin concentrations in the control and the bromocriptine-treated subjects. TRH similarly delayed the rapid decline in plasma cortisol levels in both groups of women. Basal and TRH-induced PRL levels were rapidly suppressed by bromocriptine. These studies show the presence of a paradoxical increase of beta-endorphin/beta-lipotropin and cortisol levels in response to TRH occurring shortly after delivery in normal women. This response cannot be mediated by the placenta. The absence of an inhibiting effect of bromocriptine on basal and TRH-induced beta-endorphin and cortisol release does not lend support to the hypothesis of the presence of a functionally active intermediate pituitary lobe in man early in puerperium.     

Shuttlebox avoidance in rhesus monkeys: effects on plasma cortisol and beta-endorphin

Groups of monkeys either extensively pretrained to avoid shocks in a shuttlebox or with minimal prior experience were compared for plasma cortisol and beta-endorphin levels immediately following: (1) an exposure to the box with no shock, (2) the box providing repeated inescapable shocks or (3) a re-exposure to the box, again with no shock presentation. Mere exposure to the unfamiliar box elevated plasma cortisol just as much as exposure + shock did when inexperienced monkeys were tested. However, animals with a history of previously successful shock avoidance showed smaller elevations when exposed to the box alone, than they did when inescapable shock was received. Plasma beta-endorphin levels following shuttlebox exposure showed only a sporadic pattern of elevations in either inexperienced or pretrained monkeys. However, levels of beta-endorphin as determined under control conditions in the home cage were lower in pretrained animals, as were plasma levels of cortisol. The results indicate that behavioral factors may effect plasma cortisol and beta-endorphin following both acute and chronic shuttlebox experience.