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

These studies were designed to elucidate the mechanism of inhibitory action of somatostatin (SRIF) on glucagon (IRG) and insulin (IRI) secretion. Studies were carried out in the unrecirculated isolated rat pancreas perfusion with arginine 19.2 mM and glucose 5.5 mM as stimulus primarily for IRG but also IRI secretion. The effects of excess Ca++ (15.2 mEq./L.) and excess K+ (12.8 mEq./L.) on IRG, IRI, and the SRIF-inhibited pancreas were studied. Ca++ excess in five perfusions strikingly stimulated IRG secretion (+92 per cent) but only stabilized IRI secretion compared with control perfusions. K+ excess (in seven perfusions) markedly inhibited IRG secretion (-39 per cent) while stimulating IRI secretion (+16 per cent). Restoration of normal concentrations of K+ resulted in a rebound of IRG to levels 120 per cent that of controls. SRIF, at concentrations from 0.1-20 ng./ml., produced inhibition of both IRG and IRI. In 11 perfusions, with SRIF at 10 ng./ml., IRG decreased more than IRI (-75.2 per cent IRG and -46.9 per cent IRI). In five perfusions, addition of Ca++ (15.2 mEq./L.) 10 minutes after SRIF was started resulted in a reversal of IRG inhibition to 69.4 per cent and IRI to 73.2 per cent of the arginine controls. The reversal by Ca++ of SRIF effect on IRG was greater at higher concentrations of Ca++, suggesting some form of competition. In four perfusions, excess K+ reversed SRIF-induced IRI inhibition to 79.6 per cent that of controls but had no effect on IRG inhibition. Studies in vitro with isolated islets revealed that SRIF (2 mug./ml.) inhibited 45Ca uptake of islets as did epinephrine (10(-5) M). It was concluded that SRIF-induced inhibition of hormone release appears related to an action on Ca++ uptake.
Diabetes 1976 Nov
PMID:Reversal of somatostatin inhibition of insulin and glucagon secretion. 99 24

Clofibrate 3 g/die for 10 consecutive days, significantly reduced arginine-induced IRI release in chemical diabetics and in normal controls, whether of normal body weight or obese. Blood glucose levels were not affected by clofibrate. In agreement with previous findings, it would appear that clofibrate, administered for short periods does not lead to a decrease in glucose tolerance. However, studies relating to the effect of chronic clofibrate administration in chemical diabetes are needed in order to be sure that prolonged inhibition of IRI secretion does not lead to overt diabetes.
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PMID:Inhibitory effect of clofibrate on arginine-induced insulin secretion in chemical diabetes. 102 Jun 7

Nonketotic, genetically diabetic Cinese hamsters show subnormal pancreatic insulin release and impaired suppression of glucagon in response to glucose. To study the pancreatic effects of other agents, dynamic insulin and glucagon release was measured from the in vitro perfused pancreases of normal and diabetic Chinese hamsters in response to various combinations of arginine (20mM), glucose (100 or 150 mg. per 100 ml.), and theophylline (10 mM). Theophylline alone caused identical insulin and glucagon release in diabetics and normals. Glucose, alone and in the presence of theophylline, caused subnormal insulin release and less suppression of glucagon release in the diabectics than in the normals. Arginine, in the presence of glucose and theophylline, caused excessive glucagon release but nearly normal insulin release in the diabetics. Arginine, in the absence of glucose or theophylline, caused excessive glucagon release in the diabetics and undetectable insulin release in either diabetics or normals. Pancreatic content after perfusion did not correlate with release during perfusion. Infusion of arginine alone markedly decreased the amount of extractable pancreatic insulin and glucagon. These results indicate that the pancreatic alpha cell of the diabetic Chinese hamster responds excessively to arginine, as is seen in the human diabetic. This defect is not related to acute insulin release or the presence of glucose. Further, these results confirm that the diabetic Chinese hamster's alpha and beta cells respond normally to theophylline, but are relatively insensitive to glucose.
Diabetes 1975 Mar
PMID:Responses to arginine of the perfused pancreas of the genetically diabetic Chinese hamster. 111 50

Twenty-one patients with mild maturity-onset diabetes were given introduodenal infusions of an amino acid mixture (0.5 g amino acids per kg body weight). In 9 other patients L-arginine was infused intravenously in a constant dose of 25 g. Alpha-amino nitrogen, blood glucose and plasma insulin levels were assayed under control conditions and after three days of treatment with phenformin, 150 mg daily, plus the same 150 mg dose 60 min before the second loading. Intraduodenal infusion of the amino acid mixture provoked a greater increase in plasma insulin than intravenous infusion of L-arginine, this increase being significantly inhibited by phenformin only in the first case. Since no evident influence of phenformin on the intestinal absorption of amino acids could be demonstrated, this effect may be explained by a local action on the intestinal wall exposed to high concentrations of the drug, resulting in the inhibition of the insulin secretion stimulating activity of the gut.
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PMID:The effect of phenformin on amino acid-induced insulin secretion in diabetics. 114 46

The effect of metergoline on insulin secretion has been evaluated in normal subjects and in patients with chemical diabetes. The repeated administration of metergoline, 2 mg at four-hour intervals to give a total of 24 mg, has enhanced insulin secretion in response to i.v. glucose in normal subjects but not in chemical diabetics. No changes in blood glucose pattern were observed. Under similar conditions, metergoline administration caused a slight but significant decrease in arginine-induced insulin release, both in normal subjects and in chemical diabetics. These results support the concept of a serotoninergic control of insulin secretion and suggest that serotonin exerts different effects on insulin release according to the different stimuli.
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PMID:Effect of metergoline, a powerful and long-acting antiserotoninergic agent, on insulin secretion in normal subjects and in patients with chemical diabetes. 114 50

To document and characterize the immediate phase of glucogen secretion as detected in peripheral blood in man, we have given pulses of L-arginine (0.1 gm. to 10.0 gm.) intravenously over twenty to thirty seconds to twenty-three healthy young men. Peak glucagon and insulin levels averaging four and five times basal levels respectively were reached two to five minutes after arginine administration and had returned to baseline levels by fifteen to thirty minutes. Computing the area above basal for the initial ten minutes after arginine stimulation established a dose-response relationship for the acute phases of glucagon and insulin secretion. A maximal glucagon response was elicited by doses of arginine of 5.0 gm. or greater, whereas for insulin, the plateau was reached at 2.5 gm. of arginine. Sequential 5.0-gm. pulses of arginine administered every thirty minutes showed that there was no augmentation or attenuation of the timing, magnitude (area 0-10 minutes) or absolute peak values reached for either the glucogon or insulin responses. The effect of induced hyperglycemia on the acute phase of insulin and glucagon secretion was assessed by administering the arginine during marked elevation of ambient glucose concentration achieved by the intravenous administration of glucose. This resulted in marked suppression of the acute glucagon response and dramatic accentuation of the insulin response.
Diabetes 1975 Aug
PMID:Arginine-stimulated acute phase of insulin and glucagon secretion. I. in normal man. 115 37

To investigate the aminogenic glucagon response in diabetes mellitus, arginine infusion tests were carried out on twenty-four diabetic patients before and after treatment. Eleven healthy men served as a control group. Plasma glucagon was measured by radioimmunoassay using an antiserum, G21, specific for pancreatic glucagon. Out of twenty-four patients, five were treated with diet alone, eight with sulfonylurea, and eleven with insulin. In all these diabetic groups, the glucose tolerance improved after treatment for diabetes mellitus, while the insulin response to the glucose did not show any remarkable change. The fasting levels of the plasma glucagon did not differ from that of the normal subjects both before and after treatment. Hyperresponsiveness of the plasma glucagon to arginine infusion was observed in all diabetic groups, in comparison with that of the normal controls. The exaggerated response of the plasma glucagon to arginine was lowered following appropriate treatment in each diabetic group. However, as far as the changes in glucagon area during the arginine test are concerned, the aminogenic hyperresponsiveness of the plasma glucagon was reduced prominently in the diabetic group treated with sulfonylurea. The relationship between the response of glucose and plasma insulin and between glucose and glucagon to arginine was investigated, and the importance of the changes in the insulin:glucagon ratio was emphasized. Moreover, the possibility that long-term administration of a sulfonylurea may reduce an exaggerated glucagon response to arginine was discussed.
Diabetes 1975 Sep
PMID:Glucagon response to arginine after treatment of diabetes mellitus. 115 41

Plasma glucagon response to an arginine infusion was studied in children and adolescents belonging to the following groups: (I) twenty-two controls; (II) six subjects with delayed insulin peak during oral GTT; (III) ten diabetics on diet and/or oral therapy; (IV) six newly diagnosed uncompensated diabetics; and (V) eight diabetics on insulin therapy. The fasting glucagon concentrations and rise of glucagon in response to arginine in the patients of Groups II, III and V were similar to those of the controls (Group I). The basal levels and rise of glucagon in the newly diagnosed, uncompensated dibetic children (Group IV) was elevated compared to the other groups but the difference was statistically not significant. The results of this investigation favour the hypothesis that the hyperglucagonaemia in diabetes is a secondary effect to the metabolic derangement, bearing a direct relationship to the degree of homeostastic decompensation.
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PMID:Plasma glucagon response to arginine infusion in children and adolescents with diabetes mellitus. 117 10

Studies were conducted in four normal and six diabetic children to assess the role of adrenergic blockade on basal and arginine-stimulated growth hormone and glucagon secreation. Each subject had, on three separate occasions, infusion of arginine alone or in conjunction with alpha (phentolamine) or beta (propranolol) adrenergic blockade. Clinically, there was evidence of adequate blockade by each agent. Basal hormone growth levels were not significantly different in the two groups (1.3 +/- 0.2 to 2.1 +/- 1.0 ng/ml in normal subjects; 3.0 +/- 1.1 to 6.0 +/- 3.1 ng/ml in diabetics (mean +/- 1 SEM)) but the peak growth hormone after arginine was significantly greater in the diabetic children than control subjects (34.3 +/- 7.2 versus 12.3 +/- 3.1); in both groups alpha-blockade suppressed the growth hormone response, whereas beta-blockade had no significant effect. Basal glucagon concentrations were similar in both groups (147 +/- 31 to 214 +/- 21 pg/ml in normal subjects; 100 +/- 20 to 124 +/- 17 pg/ml in diabetics on three different occasions) despite the coexistent hyperglycemia of the diabetics. Neither basal nor maximally stimulated glucagon secretion was significantly affected by alpha or beta blockade in the juvenile diabetic or control children. The results suggest that sympathetic overactivity via alpha receptors may contribute to the hypersecretion of growth hormone in juvenile diabetes and that the alpha or beta adrenergic receptor alone does not appear to modulate basal or arginine stimulated glucagon secretion.
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PMID:Effect of adrenergic blockade on glucagon and growth hormone secretion in normal and diabetic children. 120 24

Infusion of insulin (1 U/hr) for 14 hr suppressed basal glucagon levels and normalized previously excessive glucagon responses to arginine in juvenile-onset, insulin-dependent diabetic subjects, indicating that abnormal pancreatic alpha-cell function in human juvenile-onset diabetes mellitus may be a consequence of insulin lack.
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PMID:Normalization of fasting hyperglucagonemia and excessive glucagon responses to intravenous arginine in human diabetes mellitus by prolonged infusion of insulin. 120 4


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