Hyperglycemia and obesity as determinants of glucose, insulin, and glucagon responses to beta-endorphin in human diabetes mellitus.

The effect of human beta-endorphin on plasma glucose, insulin, and glucagon concentrations was studied in patients with noninsulin-dependent diabetes mellitus and in normal subjects. The subjects were divided according to their body weight into lean (body mass index, less than 25) and obese (body mass index, greater than 29.5) groups.

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.

Beta-endorphin infusion restores acute insulin responses to glucose in type-2 diabetes mellitus.

To address the possibility that an abnormality in pancreatic beta-endorphin activity might contribute to abnormal insulin secretion in diabetes mellitus, we studied the effects of beta-endorphin infusion on islet function in diabetic patients. The iv infusion of human beta-endorphin at a dose of 0.5 mg/h for 2 h in type-2 non-insulin-dependent diabetic patients (n = 12) raised plasma insulin and glucagon levels and slightly but significantly lowered plasma glucose concentrations.

Induced hyperglycemia alters antithrombin III activity but not its plasma concentration in healthy normal subjects.

The effects of induced hyperglycemia on both antithrombin III (ATIII) biologic activity and plasma concentration in normal subjects are reported. A decrease in ATIII activity parallel to hyperglycemia was observed, while ATIII concentration was unchanged. When the glycemia returned to basal values ATIII activity concomitantly showed values in the basal range.

Inhibitory effect of enkephalin on insulin secretion in healthy subjects and in non insulin-dependent diabetic subjects.

The administration of the long-acting met-enkephalin analogue (FK 33-824, Sandoz; Basel Switzerland) inhibits insulin secretion induced by glucose (oral and intravenous) and nonglucose (arginine and breakfast) secretagogues in both normal subjects and in patients with noninsulin-dependent diabetes mellitus. The plasma glucose rise triggered by oral glucose and breakfast is reduced by FK in both groups of subjects, suggesting for the opioid peptide an effect in delaying glucose absorption. The data suggest a negative role for enkephalin in the regulation of insulin secretion in both normal and noninsulin-dependent diabetic subjects.

Daily rapid blood glucose variations may condition antithrombin III biologic activity but not its plasma concentration in insulin-dependent diabetes. A possible role for labile non-enzymatic glycation.

The effect of rapid daily variation of glycemia and labile HbA1 on both antithrombin III (ATIII) activity and plasma concentration in ten insulin dependent diabetics has been evaluated. The variations of both plasma glucose and labile HbA1 were inversely correlated to the alterations of ATIII activity (r = -0.71 and r = -0.

Combined insulin and sulfonylurea therapy in non-insulin-dependent diabetics with secondary failure to oral drugs: a one year follow-up.

We studied the influence of chronic sulfonylurea treatment on glucose metabolism and beta-cell secretory activity in diabetic patients requiring insulin after secondary failure to oral drugs. Thirty diabetics were allocated at random into two groups, each consisting of 15 subjects: group A continued insulin treatment, while group B received combined insulin plus sulfonylurea. Daily doses of the sulfonylurea gliclazide ranged from 40 to 240 mg, and dose adjustment was made on the basis of periodic monthly control.

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.

Insulin induces opposite changes in plasma and erythrocyte magnesium concentrations in normal man.

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrophotometry in 10 healthy volunteers during an oral glucose tolerance test and during an euglycaemic hyperinsulinaemic glucose clamp. At min 180 and 210 of the oral glucose tolerance test, a significant decline in plasma magnesium levels (p less than 0.01 and p less than 0.

Metabolic control may alter antithrombin III activity but not its plasma concentration in diabetes: a possible role for nonenzymatic glycosylation.

The effects of metabolic control on both antithrombin III (AT III) activity and AT III plasma concentration in 20 insulin-treated diabetic subjects have been evaluated. Basal AT III activity was significantly lower in diabetic subjects versus healthy controls (P less than 0.001), whereas no difference was found in AT III concentration.

Heparin preserves antithrombin III biological activity from hyperglycemia-induced alterations in insulin-dependent diabetics.

Alteration in antithrombin III (ATIII) biological activity, despite its normal plasma concentration, in diabetic subjects is shown in this report. This alteration is glycemia level-dependent, there existing an inverse correlation between fluctuations of daily blood glucose level, labile glycosylated hemoglobin and ATIII activity. The subcutaneous and endovenous heparin administration restores ATIII activity, but does not modify its plasma concentration in diabetics.

Impaired insulin secretion in human diabetes mellitus. Effect of pharmacological activation of gamma-aminobutyric acid system.

To evaluate whether the gamma-aminobutyric acid (GABA)ergic system plays a role in the defective insulin secretion in human diabetes mellitus, 15 non-insulin-dependent diabetics with fasting hyperglycemia above 140 mg/dl were submitted to two consecutive i.v. glucose tolerance tests (IVGTT) (0.

Impaired insulin secretion in human diabetes mellitus. Interactions between naloxone, phentolamine and lysine acetylsalicylate upon glucose induced insulin release.

Non insulin-dependent diabetes mellitus (Type II) is characterized by the loss of the acute insulin response to glucose. Met-enkephalin, catecholamines and prostaglandin E (PGE) have all been reported to inhibit the acute insulin response to glucose in normal humans. To evaluate the hypothesis that an increased sensitivity to these endogenous substances may play a role in defective insulin secretion in diabetes, we evaluated the effects of three blocking drugs upon the impaired insulin response to glucose in Type II diabetic subjects, as well as glucose-induced insulin secretion in normal humans.

Interaction between epinephrine, prostaglandin E, and met-enkephalin in the regulation of insulin release in man.

Prostaglandin E (PGE), epinephrine and metenkephalin are three endogenous substances normally present in the endocrine pancreas which have been reported to inhibit glucose-induced insulin secretion in normal humans. To evaluate possible synergistic interactions between these inhibitory agents upon the regulation of insulin release in man, we examined the effects of PGE, epinephrine and the long-acting met-enkephalin analogue FK 33-824, given alone or in combination, upon glucose-induced insulin secretion in normal man. The infusion of the three agents at doses known to affect insulin secretion (10 micrograms/min, 15 ng/kg/min, 0.

Effects of salicylate, tolbutamide, and prostaglandin E2 on insulin responses to glucose in noninsulin-dependent diabetes mellitus.

To assess whether the beneficial effects of salicylates compounds and sulfonylureas on insulin secretion in patients with noninsulin-dependent diabetes mellitus could be ascribed to inhibition of prostaglandin E (PGE) synthesis, insulin responses to iv glucose pulses were determined in diabetic patients during infusion of lysine acetylsalicylate (LAS) or tolbutamide, with or without a concurrent infusion of PGE2. In these diabetic patients, the augmenting effects of LAS on glucose-induced insulin secretion were abolished by PGE2 infusion. Partial restoration by tolbutamide infusion of the first and second phases of glucose-induced insulin secretion was not affected by the administration of PGE2.

Glycemic control with an artificial pancreas improves insulin responses to both oral and glucose in nonobese noninsulin-dependent diabetic subjects.

Insulin secretory responses to both oral and intravenous glucose were investigated in 12 nonobese noninsulin-dependent diabetic subjects before and after strict metabolic control of blood glucose levels without weight loss. Glycemic control was achieved by applying an artificial pancreas to all diabetics for 2 or 3 days, which led to restoration of normal fasting blood glucose levels and to significant reduction of fasting plasma insulin (p less than 0.01) and C-peptide (p less than 0.

Normalization by sodium salicylate of the impaired counterregulatory glucagon response to hypoglycemia in insulin-dependent diabetes. A possible role for endogenous prostaglandins.

The present study was undertaken to evaluate the influence of sodium salicylate on the counterregulatory glucagon response to insulin-induced hypoglycemia in both insulin-dependent diabetic subjects (IDDM) and normal controls. The IDDM group consisted of 5 patients with recent onset of disease (less than 45 days), a normal glucagon response to hypoglycemia, and no detectable insulin antibodies (group 1); and 7 patients with duration of disease between 1 and 5 yr, a reduced glucagon response to hypoglycemia, and no insulin antibodies (group 2). Ten healthy subjects served as a control group.