Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that the hyperglucagonemia observed in diabetic animals and man may be due to an impairment of glucose uptake and metabolism by the alpha-cells resulting in a decreased production of ATP. To test this hypothesis glucose, ATP, glucagon, and insulin were measured in pancreatic islets of normal and alloxan or streptozotocin diabetic rats. Two experimental approaches were used. In the first, the pancreas was perfused in vitro for assessing insulin and glucagon release due to 10 mM amino acids with and without 5 mM glucose. These perfusions were performed in the presence and absence of insulin. After perfusion, the pancreas was frozen and processed for analysis of islet glucose, ATP, insulin, and glucagon content. The second approach was to investigate the islet sucrose, urea, and glucose spaces together with ATP, insulin, and glucagon content in vivo in normal and in insulin-treated and untreated streptozotocin diabetic rats. Perfusion of the pancreas in vitro with 5 mM glucose resulted in higher glucose content of normal islets than in alloxan and streptozotocin diabetic islets. Similarly in the in vivo studies, the intracellular glucose space of the streptozotocin diabetic islets was 30% the value found in normals. In the in vivo experiments, despite the relatively small intracellular glucose space of alpha-cell islets, the ATP content of these islets was only 15-20% lower than the ATP content of normal islets. In the in vitro experiments, perfusion with glucose resulted in ATP contents of alpha-cell islets and of normal mixed alpha-beta-cell islets which were indistinguishable. However, the ATP content of alpha-cell islets was maintained for prolonged periods in the absence of glucose in contrast to mixed islets, composed primarily of beta-cells, in which the ATP level decreased by 45% when glucose-free medium was perfused for sustained periods. Finally, insulin infused in high concentrations or administered to the diabetic animal had no effect on the glucose spaces or the ATP contents of normal or alpha-cell islets. It can be calculated that in vivo the intracellular glucose level of islets from streptozotocin treated rats is approximately 15 mM. Since in normals an extracellular glucose concentration of this magnitude inhibits stimulated glucagon release completely, it would seem unlikely that a lack of intracellular glucose is the cause of the apparent glucose "blindness" of the alpha-cells in diabetes. In fact, in perfusion studies as little as 2.5 mM free intracellular glucose was sufficient to suppress glucagon secretion from diabetic alpha-cells. The results of the ATP measurements clearly eliminate a possible energy deficit of diabetic alpha-cells as cause of the apparent glucose resistance of alpha-cells.
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PMID:Glucose and ATP levels in pancreatic islet tissue of normal and diabetic rats. 13 53

ATP stimulates glucagon and insulin secretions from the isolated perfused rat pancreas. This effect is modulated by glucose. Glucagon secretion is stimulated by ATP only in the absence or in the presence of a low glucose concentration (0.5 g/1). As to insulin secretion, it is strongly stimulated only in the presence of a glucose concentration of 1.5 g/1.
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PMID:[Adenosine triphosphate (ATP) and glucose. Action on insulin and glucagon secretion]. 13 51

Rhesus monkey pancreatic alpha-cell function in streptozotoc-induced glucose-intolerant pregnancy is similar to that in normal primate pregnancy. Specifically, basal maternal and fetal plasma glucagon levels equate, and the fetal alpha cell does not respond to the glucagonogenic stimulus of either intravenous alanine or insulin-induced hypoglycemia. This contrasts with the accelerated maturation of the fetal beta cell in glucose-intolerant pregnancy, and does not support the concept of functional coupling of the pancreatic islet by a common glucose-based process. Fetal plasma glucagon levels do increase after L-dopa injection to the fetus. These data indicate that alpha cell unresponsiveness is a function of the glucagon-releasing mechanism rather than inadequate hormonal synthesis.
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PMID:Fetal pancreatic glucagon responses in glucose-intolerant nonhuman primate pregnancy. 13 66

Adult rats were rendered diabetic by a single iv injection of streptozotocin (70 or 75 mg/kg). In these rats, serum insulin fell to minimal levels during the 48 h following drug treatment, and this was roughly paralleled by a progressive decrease in the ability of the lung to oxidize glucose. The addition of insulin to diabetic rat lung slices in vitro had no restorative effect on the depressed glucose oxidative rate during a 2 h incubation period; however, two daily treatments of the rats with 1 unit of protamine, zinc insulin completely restored lung glucose oxidation rate to normal, without significantly reducing the hyperglycemic state of the rats. An examination of the temporal changes in glucose utilization by the rat lung after acute insulin treatment revealed that the diabetic lung responded directly to serum levels of insulin, whereas the normal lung appeared to be unaffected by serum insulin levels as hihg as 87 ng/ml. The reduced rate of glucose oxidation in the diabetic lung was apparent after perfusion of the lung with glucose-free medium, and was characterized by a significant reduction in Vmax without an alteration in Km. This was attended by a depressed ability of the lung to incorporate [3H]leucine into protein and an increased ability to produce lactate, but hexose monophosphate shunt activity was normal. Specific receptors for insulin have been identified and partially characterized in crude membrane preparations of normal rat lung. The interaction of insulin with these receptors was rapid, reversible, saturable, and was dependent upon time and temperature. The binding of labeled insulin was inhibited by low concentrations of unlabeled insulin and by high concentrations of proinsulin, whereas it was unaffected by the presence of glucagon, gastrin, prolactin, ACTH, or growth hormone in microgram amounts. These observations suggest that insulin regulates the transport and utilization of glucose in the rat lung, and that this tissue contains specific receptors for insulin.
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PMID:Pulmonary insulin responsivitiy: in vivo effects of insulin on the diabetic rat lung and specific insulin binding to lung receptors in normal rats. 14 46

The decrease of insulin binding to plasma membranes of liver, adipose, and muscle tissues observed in obese-hyperglycemic (ob/ob) mice was reversed towards normal by prolonged fasting or streptozotocin treatment. The extent of this reversal was related to that of the decrease in hyperinsulinemia of the obese mice. In contrast, binding of glucagon to liver plasma membranes was little influenced by fasting or streptozotocin treatment of obese animals. The relationship between insulin binding and metabolic effects of the hormone did not appear to be identical in all tissues. In muscle, insulin binding and insulin effect on glucose uptake and metabolism changed in parallel--i.e., when binding increased, tissue sensitivity to the hormone increased. In the liver, the increase in insulin binding that followed fasting or streptozotocin treatment was not accompanied by any detectable metabolic effect of insulin on hepatic metabolism. A similar situation appeared to prevail in adipose tissue. The varying relationships observed between the state of insulin binding to membranes and the target tissue responsiveness to the hormone probably reflect the multiplicity of the factors operative in these processes and help us to understand why the over-all obese-hyperglycemic syndrome of ob/ob mice cannot be improved simply by decreasing endogenous hyperinsulinemia.
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PMID:Effect of fasting and streptozotocin in the obese-hyperglycemic (ob/ob) mouse. Apparent lack of a direct relationship between insulin binding and insulin effects. 14 Aug 28

In the 13 years since hepatic glycogen synthetase deficiency was first described in identical twins no further cases seem to have been observed. We report a child who had suffered from occasional morning convulsions since the age of 7. Three 24-hour metabolic profiles showed fasting hypoglycaemia, hyperketonaemia, but normal lactate. Hyperglycaemia and hyperlactataemia occurred after meals. Glucagon caused a rise in glucose 3 hours after a meal with a fall in lactate and alanine; no effect of glucagon was seen after a 12-hour fast. Normal increments in glucose followed oral galactose or alanine. Liver and abdominal wall muscle biopsies were taken. Glycogen content was subnormal in liver but normal in muscle. Glycogen synthetase (EC 2.4.1.11) was virtually absent from liver but fully active in muscle. Hepatic glycogen synthetase deficiency causing fasting hypoglycaemia has been confirmed. It is postulated that some children with "ketotic hypoglycaemia" may suffer from this disorder.
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PMID:Hepatic glycogen synthetase deficiency. Definition of syndrome from metabolic and enzyme studies on a 9-year-old girl. 14 12

In the presence of a glucose concentration of 1.5 g/1 the secretion of insulin from the isolated perfused rat pancreas is clearly weaker at 28 degrees C than at 37.5 degrees C. In response to cholinergic stimulation, the absolute increase of insulin secretion rate is less at 28 degrees C than at 37.5 degrees C. However, when evaluated in percentage in relation to the baseline value, this increase is more important at the lower temperature. As to glucagon secretion, lowering of the temperature from 37.5 degrees C to 28 degrees C modifies neither this secretion in the presence of glucose alone, nor the increased secretion provoked by the cholinergic stimulation.
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PMID:[Influence of temperature on the secretion of insulin and glucagon induced by stimulation of cholinergic receptors in the presence of glucose]. 14 15

D-glucose in the pyranose (ring) form exists as two anomers. The alpha-anomer is more effective than the beta-anomer in promoting insulin secretion, suppressing that of glucagon, and protecting beta-cells against alloxan toxicity. Streptozotocin (SZ), a beta cell toxin, is composed of a cytotoxic moiety, 1-methyl 1-nitrosourea, attached to carbon-2 of glucose and exists as either of two anomers in the pyranose form. In 24-hour-fasted male rats, predominantly alpha- or predominantly beta-SZ was injected intravenously and plasma glucose levels were obtained 48 hours later. The alpha-anomer produced significantly greater beta-cell necrosis at doses of 30, 35, and 40 mg./kg. body weight. At higher doses, no differences between the alpha and beta anomers were observed. 3-O-Methyl glucose (3-OMG) protected against both SZ anomers; however, the alpha-SZ remained more toxic. Larger doses of glucose protected against the lower doses of SZ and, under such conditions, the individual glucose anomers appeared equally potent. Finally, mannitol at comparable molar concentrations was ineffective in protecting against the SZ toxicity. This study suggests that streptozotocin's beta cell toxicity is mediated through recognition by the beta cell. In addition, 3-OMG and, to a lesser but significant extent, glucose were shown to protect against the streptozotocin toxicity, whereas mannitol did not.
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PMID:Pancreatic beta cell toxicity by streptozotocin anomers. 14 86

The endocrine pancreatic tissue from patients with severe primary chronic pancreatitis (n=6). secondary chronic pancreatitis due to duct obstruction by carcinoma (n=6) and non-diabetic, non-pancreatitic controls (n=4) was studied qualitatively and quantitatively using specific immunocytochemistry and electron microscopy. Grouping of variously sized islets in the sclerotic tissue (sclerosis islets), islet neoformation by ductuloinsular proliferation, and intrainsular fibrosis were the main qualitative findings. Immunocytochemical quantitation of the distribution of insulin (B), glucagon (A), somatostatin (D) and pancreatic polypeptide (PP) producing cells revealed a significant relative increase in the number of A cells and a decrease in the number of B cells of the sclerosis islets in primary chronic pancreatitis ((B-44.1+/-9.3%:A-38.3+/-2.4%:D-8.6+/-5.1%:PP-4.6+/-4.1%) as well as in secondary chronic pancreatitis B-38.0+/-14.3%:A-38.4+/-19.0%:D-9.1+/-5.8%:PP-14.5+/-23.4%) compared with controls (B-71.1+/-8.1%:A-24.3+/-5.5%:D-8.0+/-2.8%:PP-0.5+/-0.4%). The number of PP cells was significantly increased in primary chronic pancreatitis only. It is suggested that scarring of the exocrine pancreas affects islet composition, probably by impairment of the local circulation and of glucose diffusion, thus leading to reduction of the number and glucose sensitivity of B cells. The hyperplasia of A and PP cells appears to be a secondary phenomenon due to the loss of B cells.
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PMID:The endocrine pancreas in chronic pancreatitis. Immunocytochemical and ultrastructural studies. 14 59

Glucose and arginine infusion tests were performed on 12 healthy volunteers (8 males, 4 females) before and after serotoninergic activation [oral administration of L-5-hydroxytryptophan (5-HTP-) for 6 days] and serotoninergic inhibition (oral treatment with D,L-p-chloropenylalanine for 6 days). 5-HTP treatment markedly increased urinary 5-hydroxyindoleacetic acid excretion, increased the mild hyperglycemic effect of arginine infusion, and lowered the glucose disposal rate constant. The adverse effect of serotoninergic activation on glucose tolerance is not sufficiently explained by the observed changes in insulin and glucagon secretion during the fasting state and after intravenous glucose and arginine infusions. Serotoninergic inhibition did not affect the carbohydrate tolerance of normal individuals. The results of this work supports the idea that excessive indoleamine production is probably the main cause for carbohydrate intolerance in carcinoid tumors.
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PMID:Serotoninergic activation and inhibition: effects on carbohydrate tolerance and plasma insulin and glucagon. 14 82


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