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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucagon suppression by somatostatin reduces or abolishes hyperglycemia in dogs made insulin-deficient by somatostatin, alloxan, or total pancreatectomy. This suggests that the development of severe diabetic hyperglycemia requires the presence of glucagon, whether secreted by pancreatic or newly identified gastrointestinal A cells, as well as a lack of insulin. Glucagon suppression could improve therapeutic glucoregulation in diabetes.
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PMID:Glucagon: role in the hyperglycemia of diabetes mellitus. 108 99

By means of a glucose-controlled insulin- and glucose-infusion system (GCIGIS) we examined the effect of somatostatin on insulin and glucose requirements following meals or oral glucose loads in juvenile diabetics. In six of seven patients the insulin requirement with somatostatin was remarkably reduced to between 38 per cent and 79 per cent of that of otherwise identical control experiments. No reduction could be found in the seventh case, fed only 575 kcal. In all cases we observed an increase in dextrose demanded from the GCIGIS ranging between 28 per cent and 192 per cent of the control amounts. In addition, a lowering and smoothing of postprandial blood glucose curves caused by somatostatin application was a general finding. It seems to us most likely that the well-known suppression of the secretion of growth hormone and glucagon, both insulin antagonists, is responsible for the antidiabetic action of somatostatin.
Diabetes 1975 Nov
PMID:Antidiabetic action of somatostatin--assessed by the artificial pancreas. 110 69

In man, epinephrine induces increases in plasma levels of glucagon, a lipolytic and hyperglycemic hormone. To determine glucagon's contribution to this hyperglycemia and lipolysis, the effects of inhibition of pancreatic alpha-cell responses to epinephrine were investigated with somatostatin and adrenergic receptor blockade. To avoid ambiguities that might result from concomitant changes in endogenous insulin secretion, these studies were performed in juvenile-type, insulin-deficient diabetic subjects. Compared with normal subjects, the diabetics had excessive glucagon responses to epinephrine, which had been infused to attain circulating levels within the range found in man in severe stress. Both somatostatin and propranolol completely prevented glucagon responses and diminished the glycemic response to epinephrine by 40 to 50 per cent. Free fatty acid responses to epinephrine were completely prevented by propranolol but unaffected with somatostatin. Phentolamine had no effect on glucose, free fatty acid, or glucagon responses to epinephrine. These studies demonstrate that epinephrine, via a beta-adrenergic receptor mechanism, causes excessive plasma glucagon elevation in human diabetes mellitus and indicate that this hyperglucagonemia participates in the hyperglycemic, but not the lipolytic, response to epinephrine. Catecholamine-induced hyperglucagonemia may thus provide an additional explantation for the deterioration in carbohydrate tolerance associated with stress.
Diabetes 1976 Jan
PMID:Studies on the mechanism of epinephrine-induced hyperglycemia in man. Evidence for participation of pancreatic glucagon secretion. 110 95

The inhibitory effect of somatostatin on insulin, glucagon and growth hormone secretion was studied in 5 patients with diabetes mellitus. In three maturity onset diabetics, somatostatin infusion abolished the insulin rise induced by breakfast and oral glucose, and in 2 of them, inhibited the basal insulin secretion by 50% seen during control studies. Concomitantly, there was a marked and prompt reduction of glucagon levels (50%) with a sustained effect. The plasma glucose levels were either unchanged or slightly increased. Following the somatostatin infusion, there was a prompt rebound increase in both insulin and glucagon levels with a relatively stable plasma glucose concentration. In contrast, a drastic reduction of plasma glucose in face of a relatively small fall in plasma glucagon in response to somatostatin infusion was observed in 2 insulin-dependent diabetics. In all patients, the episodic release of growth hormone seen during the control day was abolished during somatostatin infusion.
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PMID:The inhibitory effect of somatostatin on growth hormone, insulin and glucagon secretion in diabetes mellitus. 115 60

The effect of glucagon suppression by somatostatin upon endogenous hyperglycemia was studied in three forms of experimental insulin deficiency in dogs: alloxan diabetes, total pancreatectomy, and diazoxide administration. In six insulin-requiring alloxan-diabetic dogs deprived of insulin for 24 hr, mean plasma glucose declined to 77% +/- 6% of the baseline level of 350 +/- 41 mg/dl during 3 hr of glucagon suppression, significantly below the unsuppressed saline controls (p less than 0.01-0.05). When somatostatin was discontinued, glucagon rose and glucose increased 21% (p less than 0.05) in 30 min. Significant correlation between maximal changes in glucagon and glucose was observed (r = 0.81; p less than 0.001). Even during a 1-hr alanine infusion in such dogs, glucose declined an average of 36 +/- 9 mg/dl, instead of rising 51 +/- 7 mg/dl as in unsuppressed controls. Maximal changes in glucagon and glucose were correlated (r = 0.85; p less than 0.01). In eight depancreatized dogs pretreated intravenously with continuous insulin and glucose infusions, withdrawal of insulin was followed by a rise in extrapancreatic glucagon; mean plasma glucose rose from 212 +/- 43 to 415 +/- 80 mg/dl 270 min after the end of the insulin infusion. However, when glucagon was suppressed after insulin withdrawal, glucose remained below 240 mg/dl, significantly less than the controls (p less than 0.005); when somatostatin was stopped, glucagon rose and glucose increased 88 +/- 19 mg/dl within an hour. The rises in glucagon and glucose were significantly correlated (r = 0.68; p less than 0.05). Glucagon suppression by somatostatin during diazoxide-induced blockade of insulin secretion in four normal dogs reduced hyperglycemia significantly but did not prevent it. The results support the hypothesis that a relative or absolute excess of glucagon, as well as a relative or absolute deficiency of insulin, is etiologically important in the development of endogenous hyperglycemia in diabetes mellitus, the hyperglucagonemia probably mediating the glucose overproduction.
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PMID:The role of glucagon in the pathogenesis of the endogenous hyperglycemia of diabetes mellitus. 118 99

Plasma glucose and glucagon responses to standard meals containing carbohydrate, fat, and protein as in normal diets were studied in 12 subjects with insulin-dependent diabetes and 12 normal subjects. Diabetics had two to three times greater glucagon responses than did normal subjects. Fifteen units of insulin injection did not normalize these excessive glucagon responses, although postprandial hyperglycemia was reduced. Infusion of somatostatin at a dosage of 500 mug/hr prevented glucagon responses and diminished postprandial hyperglycemia by 60%. The combination of insulin and somatostatin caused a progressive fall in plasma glucose levels despite meal ingestion. Somatostatin and insulin, administered subcutaneously in the same syringe, also abolished postprandial hyperglycemia. These studies indicate that excessive glucagon secretion participates in the genesis of diabetic postprandial hyperglycemia. Somatostatin, an inhibitor of glucagon secretion, may thus prove useful as an adjunct to insulin in the treatment of diabetes mellitus.
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PMID:Abnormal pancreatic glucagon secretion and postprandial hyperglycemia in diabetes mellitus. 124 53

The interaction of insulin and glucagon during infusion of somatostatin (SRIF), which suppresses secretion of these hormones, was investigated in normal, postabsorptive, concious dogs. Hepatic glucose output (production) and over-all glucose uptake by the tissues was measured with 3-3H-glucose, administered by a priming injection along with a constant infusion. Infusion of SRIF (1.5-5.0 mug/min) for 90 minutes resulted in a moderate hypoglycemia associated with a decrease in glucose production. In some animals glucose production and plasma glucose levels returned to normal before the end of SRIF infusion. Glucose uptake tended to follow plasma glucose levels. Upon termination of SRIF infusion, glucose production and uptake and plasma glucose increased sharply.
Diabetes 1976 Feb
PMID:Interaction of somatostatin, glucagon, and insulin on hepatic glucose output in the normal dog. 124 72

Fasting hypoglycemia occurred in a patient with a histologically benign mesothelioma; the serum insulin was low (2-4 muU./ml.), as was the glucose utilization rate. Splanchnic glucose output was markedly decreased on direct measurement (21 mg./min.; normal: 108-180 mg./min.). Splanchnic uptake of gluconeogenic substrates plasma glucagon was low normal during hypoglycemia and responded poorly to oral and intravenous alanine. The nonsuppressible insulin-like (NSILA-s) and somatomedin-like activities of the serum were not elevated, and the tumor did not release insulin-like activity on incubation nor did it contain somatostatin. The marked decrease in splanchnic glucose output was the principal cause of hypoglycemia, was associated with an apparent decrease in glycogenolysis, and was at least partly due to deficient glucagon secretion. The relationship of the tumor to these defects is unclear. The tumor may have secreted an unknown insulin-like material affecting primarily the liver and/or pancreatic alpha cell. The approach used here may serve as a paradigm for the analysis of hypoglycemia not caused by excessive insulin.
Diabetes 1976 Mar
PMID:Tumor hypoglycemia: deficient splanchnic glucose output and deficient glucagon secretion. 125 10

In nine children with clinically overt insulin-dependent diabetes mellitus the authors injected cyclic somatostatin (3 mug./kg. bolus, followed by infusion of 13 mug./kg. in 60 minutes) and measured blood glucose, plasma growth hormone, and glucagon concentrations throughout the infusion. The rapid administration produced no significant changes of these parameters. With the prolonged infusion there was a significant reduction of blood glucose from a mean of 148 +/- 19.7 to a mean of 88.5 +/- 18.1 mg./100 ml. (P less than 0.005) and of plasma glucagon from a basal mean of 33.3 +/- 2.4 to a minimum mean of 22.1 +/- 1.7 pg./ml. (P less than 0.01). There was a statistically significant correlation between the two parameters (0.01 less than P less than 0.05). Plasma GH values also diminished during the infusion, but the reduction was not statistically significant. These results show that somatostatin lowers blood glucose concentrations as a secondary effect of inhibition of glucagon secretion. Somatostatin is not suitable for therapy in diabetes. We speculate that a similar substance with a more prolonged and specific action on glucagon might prove of practical value in the treatment of diabetes mellitus.
Diabetes 1976 Jul
PMID:Effect of somatostatin on blood sugar, plasma growth hormone, and glucagon levels in diabetic children. 127 5

Basal serum growth hormone and response of GH to GRF in 10 patients with noninsulin-dependent diabetes and in 10 control subjects were studied. The basal GH level in NIDDM was higher than that in control subjects. There was a significant difference. After an intravenous bolus of hGRF 1-29 NH2 with the dose of 1 microgram/kg body weight, GH (Peak level-basal level) decreased in NIDDM patients in comparing with control group (P < 0.05). These findings may suggest that the pituitary GH reserve is reduced in patients with NIDDM. There exists some defect in central GH control in diabetics with enhanced somatostatin secretion and abnormal sensitivity of the GH secretion cells to a variety of regulatory factors including GRF, glucose, amino-acids, free fat acid.
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PMID:[Blunted growth hormone response to hGRF 1-29 NH2 in patients with non-insulin-dependent diabetes mellitus]. 130 83


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