Rise In Plasma Glucose Concentration Research Articles

Plasma insulin is required for the increase in plasma angiopoietin-like protein 8 in response to nutrient ingestion.

Plasma levels of angiopoietin-like protein 8 (ANGPTL8) are regulated by feeding and they increase following glucose ingestion. Because both plasma glucose and insulin increase following food ingestion, we aimed to determine whether the increase in plasma insulin and glucose or both are responsible for the increase in ANGPTL8 levels. ANGPTL8 levels were measured in 30 subjects, 14 with impaired fasting glucose (IFG), and 16 with normal fasting glucose (NFG); the subjectsreceived 75g glucose oral Glucose tolerance test (OGTT), multistep euglycaemic hyperinsulinemic clamp and hyperglycaemic clamp with pancreatic clamp. Subjects with IFG had significantly higher ANGPTL8 than NGT subjects during the fasting state (p<0.05). During the OGTT, plasma ANGPTL8 concentration increased by 62% above the fasting level (p<0.0001), and the increase above fasting in ANGPTL8 levels was similar in NFG and IFG individuals. During the multistep insulin clamp, there was a dose-dependent increase in plasma ANGPTL8 concentration. During the 2-step hyperglycaemic clamp, the rise in plasma glucose concentration failed to cause any change in the plasma ANGPTL8 concentration from baseline. In response to nutrient ingestion, ANGPTL8 level increased due to increased plasma insulin concentration, not to the rise in plasma glucose. The incremental increase above baseline in plasma ANGLPTL8 during OGTT was comparable between people with normal glucose tolerance and IFG.

Decreased basal hepatic glucose uptake in impaired fasting glucose.

This research aimed to define the pathophysiological defects responsible for the elevated fasting plasma glucose (FPG) concentration and excessive rise in post-load plasma glucose observed in individuals with impaired fasting glucose (IFG). We used tracer techniques to quantify basal splanchnic (primarily hepatic) glucose uptake and glucose fluxes following glucose ingestion in individuals with normal glucose tolerance (NGT; n=10) and IFG (n=10). Individuals with IFG had a comparable basal rate of hepatic glucose production to those with NGT (15.2±0.2 vs 18.0±0.8μmolmin-1[kg lean body mass (LBM)]-1; p=0.09). However, they had a significantly reduced glucose clearance rate during the fasting state compared with NGT (2.64±0.11 vs 3.62±0.20ml min-1[kgLBM]-1; p<0.01). The difference between the basal rate of glucose appearance measured with [3-3H]glucose and [1-14C]glucose, which represent basal splanchnic glucose uptake, was significantly reduced in IFG compared with NGT (1.39±0.28 vs 3.16±0.44μmolmin-1[kgLBM]-1; p=0.02). Following glucose ingestion, the total amount of exogenous glucose that appeared in the systemic circulation was not significantly different between groups. However, suppression of endogenous glucose production (EGP) was markedly impaired in individuals with IFG. These results demonstrate that decreased tissue (liver) glucose uptake, not enhanced EGP, is the cause for elevated FPG concentration in individuals with IFG, while the excessive rise in plasma glucose concentration following a glucose load in these individuals is the result of impaired suppression of hepatic glucose production.

Remogliflozin Etabonate, a Selective Inhibitor of the Sodium-Glucose Transporter 2, Improves Serum Glucose Profiles in Type 1 Diabetes

OBJECTIVERemogliflozin etabonate (RE), an inhibitor of the sodium-glucose transporter 2, improves glucose profiles in type 2 diabetes. This study assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of RE in subjects with type 1 diabetes.RESEARCH DESIGN AND METHODSTen subjects managed with continuous subcutaneous insulin infusion were enrolled. In addition to basal insulin, subjects received five randomized treatments: placebo, prandial insulin, 50 mg RE, 150 mg RE, and mg RE 500.RESULTSAdverse events and incidence of hypoglycemia with RE did not differ from placebo and prandial insulin groups. RE significantly increased urine glucose excretion and reduced the rise in plasma glucose concentration after oral glucose. RE reduced incremental adjusted weighted mean glucose (0–4 h) values by 42–49 mg/dL and mean glucose (0–10 h) by 52–69 mg/dL.CONCLUSIONSRE can be safely administered with insulin in type 1 diabetes and reduces plasma glucose concentrations compared with placebo.

Ghrelin Modulates Sympathetic Nervous System Activity and Stress Response in Lean and Overweight Men

Ghrelin is a growth hormone-releasing peptide secreted by the stomach with potent effects on appetite. Experimental and clinical studies indicate that ghrelin also influences cardiovascular regulation and metabolic function and mediates behavioral responses to stress. We investigated the effects of ghrelin on blood pressure (BP), sympathetic nervous system activity, and mental stress responses in lean (n=13) and overweight or obese (n=13) individuals. Subjects received an intravenous infusion of human ghrelin (5 pmol/kg per minute for 1 hour) and saline in a randomized fashion. Ghrelin decreased systolic (-6 and -11 mm Hg) and diastolic BP (-8 mm Hg for both), increased muscle sympathetic nervous system activity (18±2 to 28±3 bursts per min, P<0.05 and from 21±2 to 32±3 bursts per min, P<0.001) in lean and overweight or obese subjects, respectively, without a significant change in heart rate, calf blood flow, or vascular resistance. Ghrelin induced a rise in plasma glucose concentration in lean individuals (P<0.05) and increased cortisol levels in both groups (P<0.05). Stress induced a significant change in mean BP (+22 and +27 mm Hg), heart rate (+36 and +29 bpm), and muscle sympathetic nervous system activity (+6.1±1.6 and +6.8±2.7 bursts per min) during saline infusion in lean and overweight or obese subjects, respectively. During ghrelin infusion, the changes in BP and muscle sympathetic nerve activity in response to stress were significantly reduced in both groups (P<0.05). In conclusion, ghrelin exerts unique effects in that it reduces BP and increases muscle sympathetic nervous system activity and blunts cardiovascular responses to mental stress. These responses may represent a combination of peripheral (baroreflex-mediated) and central effects of ghrelin.

Plasma Glucose After Stomach or Jejunum Glucose Infusion in Roux-En-Y Gastric Bypass Patients – a Possible Implication for Early Satiety Mechanism

Morbidly obese patients undergoing gastric bypass surgery experience early satiety soon after the surgery; the mechanism of this effect is poorly understood. As blood glucose concentration plays a role in appetite regulation in humans, we hypothesized that after gastric bypass surgery glucose absorbed mainly in jejunum leads to a greater rise in plasma glucose that if it is ingested in stomach. 24 non-diabetes morbidly obese patients (15 women, 9 men, mean age [± SD] 35.6 ± 11.9 years, body weight 140.7 ± 33.1 kg, BMI 46.8 ± 8.3 kg/m²) undergoing Roux-en-Y gastric bypass surgery were given 10 ml of 40% glucose solution to the stomach before its size reduction and to the jejunum after gastro-jejunal anastomosis was formed. After jejunal infusion blood glucose increased more rapidly and was ∼30% higher than after stomach infusion. Moreover, this increase was less pronounced in more obese patients. In patients after Roux-en-Y gastric bypass surgery glucose absorbed in jejunum leads to greater rise in plasma glucose concentration than if it is ingested in stomach. This phenomenon may help explain satiety feeling occurring early in gastric bypass surgery patients.

The Inhibition of Lipase and Glucosidase Activities by Acacia Polyphenol

Acacia polyphenol (AP) extracted from the bark of the black wattle tree (Acacia mearnsii) is rich in unique catechin-like flavan-3-ols, such as robinetinidol and fisetinidol. In an in vitro study, we measured the inhibitory activity of AP on lipase and glucosidase. In addition, we evaluated the effects of AP on absorption of orally administered olive oil, glucose, maltose, sucrose and starch solution in mice. We found that AP concentration-dependently inhibited the activity of lipase, maltase and sucrase with an IC50 of 0.95, 0.22 and 0.60 mg ml−1, respectively. In ICR mice, olive oil was administered orally immediately after oral administration of AP solution, and plasma triglyceride concentration was measured. We found that AP significantly inhibited the rise in plasma triglyceride concentration after olive oil loading. AP also significantly inhibited the rise in plasma glucose concentration after maltose and sucrose loading, and this effect was more potent against maltose. AP also inhibited the rise in plasma glucose concentration after glucose loading and slightly inhibited it after starch loading. Our results suggest that AP inhibits lipase and glucosidase activities, which leads to a reduction in the intestinal absorption of lipids and carbohydrates.

EFFECTS OF GHRELIN INFUSION ON SYMPATHETIC NERVOUS SYSTEM ACTIVITY IN HUMANS: PP.32.256

Ghrelin is a recently discovered GH-releasing peptide secreted by the stomach with effects on appetite and cardiovascular regulation. Animal studies suggest that ghrelin acts centrally to decrease the activity of the sympathetic nervous system (SNS) and may have a role in mediating behavioural responses to stress. To investigate the effects of ghrelin in humans, we gave 9 lean healthy men (age 21 ± 0.3 years) an intravenous infusion of human ghrelin (5pmol/kg/min for 1 hour) and saline in a randomized fashion. Ghrelin elicited a small decrease in systolic and diastolic blood pressure (-12 mmHg vs -4 mmHg for systolic and -12 ± 1 mmHg vs -6 ± 1 mmHg for diastolic, during ghrelin and saline infusion respectively, P < 0.05) without a significant change in heart rate or cardiac output. Ghrelin infusion resulted in a marked increase in muscle sympathetic nervous activity (MSNA), measured by microneurography (from 18 ± 2 to 26 ± 4 bursts per min, P < 0.05) while no change occurred during saline infusion (from 18 ± 2 to 17 ± 1 bursts per min). Ghrelin, but not saline, induced a rise in plasma glucose concentration (from 4.4 ± 0.1 to 4.8 ± 0.1 mmol/l, P < 0.05). A stress test consisting of 5-min of forced mental arithmetic was performed following the infusion of saline and ghrelin. During saline, stress induced a significant change in mean blood pressure (+24 mmHg), heart rate (+21 bpm) and MSNA (+33%, P < 0.05). During ghrelin infusion, the changes in heart rate were similar but the changes in blood pressure and MSNA were significantly reduced compared with saline infusion (+18 mmHg and -9% in MSNA, P < 0.05). These results indicate that in healthy human, ghrelin-induced decrease in blood pressure is accompanied by a marked increase, rather than a decrease, in SNS activity. We hypothesize that ghrelin activates the SNS through baroreceptor unloading as a result of a peripheral vasodilatory effect rather than by affecting the central nervous system. Furthermore, ghrelin may contribute to the stress induced cardiovascular responses.

A novel dairy-derived isolate that inhibits adipogenesis and significantly reduces weight gain in a high fat animal model

A novel, highly enriched bioactive bovine whey protein fraction (LAP001) was shown to directly inhibit adipocyte differentiation and lipid accumulation over a wide concentration range. Further in vitro characterisation showed that LAP001 suppressed induction of PPARγ expression in a dose-dependent manner. Administration of LAP001 to rats maintained on a high-fat diet over a 28-day period led to a significant reduction in weight gain and prevented a rise in plasma glucose concentration without significantly affecting plasma insulin concentrations. In additional, there was a beneficial modulation of major serum adipokines (decreased leptin and increased adiponectin concentration) that impact on metabolic parameters related to obesity. As such, LAP001 represents a novel and potentially attractive dairy-derived fraction for further development and testing as an agent that can inhibit weight gain, and aid in the control of obesity-related metabolic disorders.

Suprachiasmatic GABAergic inputs to the paraventricular nucleus control plasma glucose concentrations in the rat via sympathetic innervation of the liver.

Daily peak plasma glucose concentrations are attained shortly before awakening. Previous experiments indicated an important role for the biological clock, located in the suprachiasmatic nuclei (SCN), in the genesis of this anticipatory rise in plasma glucose concentrations by controlling hepatic glucose production. Here, we show that stimulation of NMDA receptors, or blockade of GABA receptors in the paraventricular nucleus of the hypothalamus (PVN) of conscious rats, caused a pronounced increase in plasma glucose concentrations. The local administration of TTX in brain areas afferent to the PVN revealed that an important part of the inhibitory inputs to the PVN was derived from the SCN. Using a transneuronal viral-tracing technique, we showed that the SCN is connected to the liver via both branches of the autonomic nervous system (ANS). The combination of a blockade of GABA receptors in the PVN with selective removal of either the sympathetic or parasympathetic branch of the hepatic ANS innervation showed that hyperglycemia produced by PVN stimulation was primarily attributable to an activation of the sympathetic input to the liver. We propose that the daily rise in plasma glucose concentrations is caused by an SCN-mediated withdrawal of GABAergic inputs to sympathetic preautonomic neurons in the PVN, resulting in an increased hepatic glucose production. The remarkable resemblance of the presently proposed control mechanism to that described previously for the control of daily melatonin rhythm suggests that the GABAergic control of sympathetic preautonomic neurons in the PVN is an important pathway for the SCN to control peripheral physiology.

Can plasma glucose and nonesterified fatty acid be regulators of glucose utilization in skeletal muscle?

The effect of plasma glucose and nonesterified fatty acid (NEFA) on basal and insulin-stimulated glucose utilization in skeletal muscle was assessed by perfused hindlimb preparations. Two-month-old male Wistar rats were divided into four groups: starved, glucose-loaded, hypoglycemic and control. Diabetic rats were made by means of streptozotocin, and divided into three groups: non-treated, insulin-treated normoglycemic and insulin-treated hyperglycemic. The effect of NEFA on glucose clearance was also investigated by adding palmitate to the perfusate. Basal glucose utilization decreased with a rise in plasma glucose concentrations, and increased with a fall in them in each group. The available data strongly support the view that plasma glucose levels play an important role in the control of basal glucose utilization by the hindlimb muscle. In contrast, continuous hyperglycemia in the diabetic state decreased insulin-stimulated glucose utilization by the skeletal muscle, whereas an acute rise in plasma glucose concentrations in the glucose-load state did not. Palmitate stimulated basal glucose utilization, while it decreased insulin-stimulated glucose uptake. It was also clarified that it increased the affinity for glucose in the skeletal muscle in the basal state. This finding seems to indicate that NEFA has some influence on an increase in basal glucose utilization in starvation.

Clinical evaluation of an infusion of xylazine, guaifenesin and ketamine for maintenance of anaesthesia in horses

General anaesthesia was maintained in 40 horses by the continuous intravenous infusion of a mixture of 500 ml 10% guaifenesin solution, 1 g ketamine and 500 mg xylazine. The median duration of infusion was 65 mins (interquartile range 51-95 mins). Anaesthesia was characterised by active palpebral reflexes, variable degrees of nystagmus and occasional swallowing. Swallowing was considered to be undesirable in horses undergoing laryngeal surgery, but the infusion produced satisfactory conditions for all other surgical procedures performed. Arterial blood pressure was well maintained in all cases (median mean arterial blood pressure = 85 mmHg after 30 mins anaesthesia). Heart rate and PaCO2 were significantly lower, whilst PaO2 was significantly higher in the infusion group than in a group of paired control horses which were anaesthetised with halothane. Recovery from anaesthesia was good (Grades 1-2) in 33 horses. Median times to sternal recumbency and to standing were 24 and 38 mins respectively. The infusion caused a significant fall in packed cell volume, haemoglobin concentration and red blood cell count (P < 0.01) and a significant rise in plasma glucose concentration (P < 0.01). These variables returned to pre-infusion values within 24 h.

Plasma growth hormone levels in fed and fasted rainbow trout (Oncorhynchus mykiss) are decreased following handling stress

Plasma growth hormone concentrations of rainbow trout,Oncorhynchus mykiss, fasted for six weeks, were significantly (p < 0.01) higher than in comparable fed animals; in the fasted fish, the levels fell progressively following acute stress (by displacing the fish within their home aquarium), with significant differences from pre-stressed fish evident between one and thirty-two hours after application of the stressor. Plasma growth hormone concentrations also fell significantly in the fed group, but differences were evident only between two and eight hours after stressor application.Plasma cortisol concentrations in pre- and post-stressed fed and fasted fish were similar. There was a bimodal response to stressor application in both groups, with significantly higher values relative to the pre-stressed sample evident one and eight hours after disturbance, but not after two, four or thirty-two hours. The changes in plasma cortisol levels between the initial (09:00h) sample and the sample taken eight hours later resembles the diet pattern seen in trout given access to self-demand feeders.Plasma glucose concentrations in pre-stressed fed animals were higher than in pre-stressed fasted fish. This relationship was also evident between one and four hours and thirty-two hours after stressor application. The post-stress rise in plasma glucose concentration was evident between one and four hours in the fed group, and between four and eight hours in fasted fish.The diel changes in plasma growth hormone and glucose concentrations could not be attributed to normal circadian patterns, and there was no apparent correlation between changes in plasma growth hormone and cortisol concentrations. There was a significant inverse correlation between plasma glucose and growth hormone concentrations when the total data set were analyzed, but these correlations were not apparent when the treatment groups were analyzed separately.

8–37hCGRP, an amylin receptor antagonist, enhances the insulin response and perturbs the glucose response to infused arginine in anesthetized rats

When 2 mmol L-arginine was infused into non-fasted, anesthetized rats at a rate slow enough to avoid hemodynamic disturbance, there was a rise in plasma glucose concentration followed by a decline to pre-infusion levels. In animals pre-infused with 8-37hCGRP, a fragment of calcitonin gene-related peptide that blocks amylin's hyperglycemic action, the normal initial rise in plasma glucose was accompanied by an enhanced rise in plasma insulin and was then followed by an enhanced fall in plasma glucose. These perturbations of the insulin and glucose response during amylin receptor blockade are difficult to explain without invoking a role for endogenous amylin; they further suggest an autocrine/paracrine role for amylin at the pancreatic islet.

The effects of different plasma insulin concentrations on lipolytic and ketogenic responses to epinephrine in normal and type 1 (insulin-dependent) diabetic humans.

This study was performed to verify: (1) the ability of different insulin concentrations to restrict the lipolytic and ketogenic responses to exogenous epinephrine administration; (2) whether the ability of insulin to suppress the lipolytic and ketogenic responses during epinephrine administration is impaired in Type 1 (insulin-dependent) diabetic patients. Each subject was infused on separate occasions with insulin at rates of 0.2, 0.4, and 0.8 mU.kg-1.min-1 while normoglycaemic. To avoid indirect adrenergic effects on endocrine pancreas secretions, the so-called "islet clamp" technique was used. Rates of appearance of palmitic acid, acetoacetate, and 3-hydroxybutyrate were simultaneously measured with an infusion of 13C-labelled homologous tracers. After a baseline observation period epinephrine was exogenously administered at a rate of 16 ng.kg-1.min-1. At low insulin levels (20 microU/ml) the lipolytic response of comparable magnitude was detected in normal and Type 1 diabetic patients. However, the ketogenic response was significantly higher in Type 1 diabetic patients. During epinephrine administration, similar plasma glucose increments were observed in the two groups (from 4.74 +/- 0.53 to 7.16 +/- 0.77 mmol/l (p less than 0.05) in Type 1 diabetic patients and from 4.94 +/- 0.20 to 7.11 +/- 0.38 mmol/l (p less than 0.05) in normal subjects, respectively). At intermediate insulin levels (35 microU/ml) no significant differences were found between Type 1 diabetic patients and normal subjects, whereas plasma glucose levels rose from 4.98 +/- 0.30 to 6.27 +/- 0.66 mmol/l (p less than 0.05) in Type 1 diabetic patients, and from 5.05 +/- 0.13 to 6.61 +/- 0.22 mmol/l (p less than 0.05) in normal subjects. At high insulin levels (70 microU/ml) the lipolytic response was detectable only in Type 1 diabetic patients; the ketogenic response was reduced in both groups. During the third clamp, a significant rise in plasma glucose concentration during epinephrine infusion was observed in both groups. In conclusion this study shows that at low insulin levels Type 1 diabetic patients show an increased ketogenic response to epinephrine, despite their normal nonesterified fatty acid response. Instead, high insulin levels are able to restrict the ketogenic response to epinephrine in both normal and Type 1 diabetic subjects, although there is a still detectable lipolytic response in the latter. In the presence of plasma free insulin levels that completely restrict the ketogenic response in the same group, there is still a distinct glycaemic response. Plasma insulin levels in Type 1 diabetic patients are a major determinant of the metabolic response to epinephrine.

Incorporation of fatty acids from fish oil and olive oil into colonic mucosal lipids and effects upon eicosanoid synthesis in inflammatory bowel disease.

The incorporation of the fatty acids in fish and olive oil into the colonic mucosa of patients with inflammatory bowel disease was examined during 12 weeks' dietary supplementation with the oils, and the influence on colonic mucosal prostaglandin and thromboxane generation was measured. With a dietary supplement of 18 g fish oil daily, concentrations of the major polyunsaturated fatty acids in fish oil, eicosapentaenoic acid and docosahexaenoic acid, were significantly raised in mucosal lipids. The first time these were measured, after three weeks' supplementation, the mean increases in eicosapentaenoic and docosahexaenoic acid were seven fold and 1.5 fold respectively, and these increases were maintained during the 12 week study. Arachidonic acid values fell throughout the study and this reduction was significant at 12 weeks. Mucosal prostaglandin E2 (PGE2), thromboxane B2, and 6-keto prostaglandin F1 alpha synthesis were suppressed, and this reached significance (p less than 0.05) at three and 12 weeks for PGE2 and at 12 weeks for thromboxane B2. The predominant fatty acid in olive oil is oleic acid. Supplementation with 18 g/day resulted in a significant increase in oleic acid in colonic mucosa at 12 weeks (p less than 0.05) and a fall in stearic acid and docosahexaenoic acid; there was no significant change in eicosanoid synthesis. It is concluded that colonic lipids and prostaglandin and thromboxane synthesis can be readily altered by dietary supplementation with fish oil. The extent of incorporation of the fatty acids present in oils is dependent upon the individual fatty acid.

Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans

To evaluate the role of tumor necrosis factor (TNF) in the initiation of the metabolic response to acute infection, we performed a crossover saline-controlled study in six healthy postabsorptive men, investigating the metabolic effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a transient stress hormone response, associated with an early and sustained rise in plasma glucose concentrations (percentage increase at 2 h 23 +/- 7; P less than 0.05). Glucose turnover, measured 7.5 h postinjection, was 10 +/- 3% higher after TNF administration (P less than 0.05). Plasma free fatty acids (FFA) and glycerol concentrations increased transiently after TNF injection, peaking after 4 h (percentage increase 363 +/- 83 and 67 +/- 14, respectively; both P less than 0.05). FFA turnover, determined 6.5 h postinjection, increased in five subjects to a variable extent (percentage increase 126 +/- 55; P less than 0.05). Finally, resting energy expenditure showed a transient rise after TNF injection (34 +/- 2% at 4 h; P less than 0.05). We conclude that intravenous TNF reproduces many of the metabolic changes observed in septicemia, suggesting that TNF may be an initiating factor in the development of the metabolic response to acute infection.

Metabolic effects of cortisol, ACTH, adrenalin and insulin in the marsupial sugar glider, Petaurus breviceps

The effects of cortisol, ACTH, adrenalin and insulin on indices of carbohydrate, fat and protein metabolism were investigated in the conscious marsupial sugar glider Petaurus breviceps. Short-term i.v. infusion of cortisol at dose rates of 0.02, 0.2 and 1.0 mg/kg per h caused the plasma glucose concentration to rise sharply from the normal range of 3.3-4.4 to 8.1-8.7 mmol/l at the end of the infusion period without significant alteration in plasma free fatty acid (FFA), amino acid or urea concentrations. Infusions of ACTH at dose rates of 0.02, 0.06 and 0.45 IU/kg per h caused a similar rise in plasma glucose concentration; however, this was now accompanied by an elevation in plasma FFA concentration, but again without significant changes in either plasma amino acid or urea concentrations. Infusion of adrenalin at 10 micrograms/kg per h caused an increase in the plasma concentrations of both glucose and FFA. Intravenous injections of 0.15 IU insulin/kg caused a rapid and marked decrease in the plasma glucose concentration within 30 min and an increase in the plasma free cortisol concentration. Associated with this change was a marked rise in the plasma concentration of both FFA and free cortisol. The rise in free cortisol was, however, significantly reduced by infusion of glucose. Pretreatment with five daily i.m. injections of 1 mg cortisol acetate/kg, which produced an increase in plasma free cortisol concentration to near the maximum of the physiological range, caused a marked reduction in insulin sensitivity. Cortisol pretreatment caused an increase in the plasma FFA and amino acid concentrations. Petaurus breviceps is highly sensitive to the metabolic effects of glucocorticoids and is similar in this respect to the brush-tailed possum Trichosurus vulpecula. The interactive effects between insulin and glucocorticoids on carbohydrate, fat and protein metabolism in Petaurus breviceps are similar to those shown by Trichosurus vulpecula and some eutherian mammals but contrast with the pattern described for two macropodid marsupials, the red kangaroo Macropus rufus and the quokka Setonix brachyurus.

Beta-endorphin-induced inhibition and stimulation of insulin secretion in normal humans is glucose dependent.

This study evaluated the effect of human beta-endorphin on pancreatic hormone levels and their responses to nutrient challenges in normal subjects. Infusion of 0.5 mg/h beta-endorphin caused a significant rise in plasma glucose concentrations preceded by a significant increase in peripheral glucagon levels. No changes occurred in the plasma concentrations of insulin and C-peptide. Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by beta-endorphin infusion (P less than .01). This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. beta-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine. To verify whether the modification of prestimulus glucose level could be important in these hormonal responses to beta-endorphin, basal plasma glucose concentrations were raised by a primed (0.5 g/kg) continuous (20 mg kg-1.min-1) glucose infusion. After stabilization of plasma glucose levels (350 +/- 34 mg/dl, t = 120 min), beta-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 +/- 9 microU/ml, P less than .01), which remained elevated even after the discontinuation of opioid infusion. Moreover, the acute insulin response to a glucose pulse (0.33 g/kg i.v.) given during beta-endorphin infusion during hyperglycemia was significantly higher than the response obtained during euglycemia (171 +/- 32 vs. 41 +/- 7 microU/ml, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Primary role of glucagon release in the effect of beta-endorphin on glucose homeostasis in normal man.

The present study aimed at evaluating the effect of human beta-endorphin on pancreatic hormone levels and on glucose metabolism in normal subjects. Infusion of 143 nmol/h beta-endorphin in 7 subjects caused a significant rise in plasma glucose concentrations (+ 1.7 +/- 0.3 mmol/l) which was preceded by a significant increase in peripheral plasma glucagon levels (+ 44 +/- 13 ng/l). No changes occurred in the plasma concentrations of insulin and catecholamines (adrenaline and noradrenaline). The influence of beta-endorphin per se on glucose homeostasis was studied in 7 other subjects using the euglycaemic clamp technique in which the endocrine pancreatic function was fixed at its basal level with somatostatin together with replacement of basal insulin and glucagon by the exogenous infusion of these hormones. In this new metabolic conditions, beta-endorphin failed to have significant influences on the various parameters of tracer-estimated glucose metabolism (production, utilization, and clearance) and on the plasma levels of the gluconeogenic precursors (glycerol and alanine). Moreover, the levels of pancreatic and counterregulatory hormones (cortisol and catecholamines) were not different between beta-endorphin and control studies. We conclude that the naturally occurring opioid peptide beta-endorphin produced an hyperglycaemic effect in man which appears to be mediated by glucagon. The opioid seems to have no direct effect on glucose metabolism. These results suggest that the metabolic effects of beta-endorphin in normal man are secondary to its impact on pancreatic hormone secretion and not a consequence of a direct modulation of glucose metabolism.

Impaired insulin response to glucose but not to arginine in heroin addicts.

Plasma glucose, insulin, glucagon and growth hormone responses to both oral glucose and iv arginine were evaluated in 15 heroin addicts and 15 control subjects matched for age, sex and weight. The heroin users had an exaggerated rise in plasma glucose concentrations following oral sugar, which persisted until the end of the study (102 +/- 5 mg/dl in addicts vs 72 +/- 3 mg/dl in controls at 240 min, p less than 0.01) and significantly lower insulin responses (insulin peak 28 +/- 4 microU/ml in addicts vs 67 +/- 8 microU/ml in controls, p less than 0.01). The inhibitory effect of glucose on glucagon concentrations was less evident in addicts than in controls. The responses of plasma glucose, insulin and glucagon to arginine were not significantly different between addicts and controls, while the growth hormone rise was significantly greater in addicts. These results demonstrate that heroin users have impaired insulin secretion to oral glucose but not to arginine and suggest that: the impaired insulin secretion in heroin addicts is not dependent on beta-cell exhaustion, and a selective inhibition of glucose-induced insulin secretion is operative in these subjects, as it happens in patients with noninsulin-dependent diabetes mellitus.