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)

A somatostatin analog, [D-Ala5, D-Trp8]-somatostatin, has been found to selectively inhibit insulin and GH release in rats. The release of these hormones is inhibited by an analog dose of 5 microgram/kg in short term experiments (15 min from analog administration to blood sampling), while glucagon levels are not lowered by analog doses as high as 500 microgram/kg. The lowered insulin to glucagon ratio results in hyperglycemia. [D-Ala5, D-Trp8]Somatostatin is also long acting; a 1 mg/kg dose results in hypoinsulinemia for 2 h and hyperglycemia for 3 h.
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PMID:Prolonged suppression of insulin release by a somatostatin analog. 74 88

The effect of diabetes on rat hepatic ornithine decarboxylase (ODC) activity was studied in male rats 4 h to 8 days after the ip or iv administration of streptozotocin. Hepatic ODC activity increased 4-fold above control on the fourth day of diabetes. Increased ODC activity was observed with a dose of streptozotocin (70 mg/kg iv) which increased plasma ketones and glucagon and reduced plasma insulin. No change was seen with doses causing only mild hyperglycemia without change in plasma ketones, glucagon, or insulin. Insulin therapy prevented the increase in hepatic ODC activity in diabetic rats. Adrenalectomy or hypophysectomy also prevented the diabetes-associated increase of ODC activity. The studies suggest that insulin deficiency may result in increased hepatic polyamine synthesis.
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PMID:Effect of streptozotocin-induced diabetes on hepatic ornithine decarboxylase activity in the rat. 74 42

The respective roles of glucose and insulin in the regulation of glucagon release from the canine stomach were investigated using an isolated blood-perfused preparation. At normal blood glucose and plasma insulin levels, the stomach released small amounts of glucagon. Such basal gastric glucagon release was not modified by hyperglycemia. In contrast, gastric glucagon release was increased by hypoglycemia or 2-deoxy-D-glucose-induced cytoglycopenia. Antibody neutralization of basal circulating concentrations of insulin (10 +/- 1 microU/ml) doubled the stimulation induced by hypoglycemia alone. It is concluded that: 1) suppression of gastric glucagon release is observed with very low concentrations of insulin; 2) basal gastric glucagon release is not further suppressed by hyperglycemia; and 3) that hypoglycemia and cytoglycopenia stimulate gastric glucagon secretion.
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PMID:Glucose and insulin in the regulation of glucagon release from the isolated perfused dog stomach. 74 4

Effects of somatostatin on extrapancreatic glucagon secretion in totally depancreatized dogs were examined. Somatostatin infusion at a rate of 3 microgram/min showed a rapid decrease of total glucagon-like immunoreactive materials (total GLI) measured by nonspecific antiserum, AGS 10, and gut glucagon immunoreactivity (gut GI) measured by specific antiserum, AGS 18, in systemic blood. Gut GLI calculated as the difference between total GLI and GI did not decrease significantly within 30 min. No changes of blood glucose were noted. Significant decreases of all glucagon fractions were observed when the rate of somatostatin infusion was increased to 10 microgram/min and prolonged for 90 min, whereas again blood glucose did not change at all. It is concluded that somatostatin inhibits both gut GI and GLI secretion, although gut GLI remains in circulation longer than gut GI. Suppression of gut GI is not effective for the reduction of blood glucose once an extreme hyperglycemia is brought about by insulin deficiency.
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PMID:Failure of somatostatin to decrease blood glucose by suppression of extrapancreatic glucagon in severely diabetic depancreatized dogs. 75 98

To evaluate the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia, the counterregulatory hormones, glucagon, epinephrine, and cortisol were infused alone as well as in double and triple combinations into normal conscious dogs in doses that were designed to simulate changes observed in severe stress. Infusion of glucagon, epinephrine, or cortisol alone produced only mild or insignificant elevations in plasma glucose concentration. In contrast, the rise in plasma glucose produced by combined infusion of any two counterregulatory hormones was 50-215% greater (P < 0.005-0.001) than the sum of the respective individual infusions. Furthermore, when all three hormones were infused simultaneously, the increment in plasma glucose concentration (144+/-2 mg/dl) was two- to fourfold greater than the sum of the responses to the individual hormone infusions or the sum of any combination of double plus single hormone infusion (P < 0.001). Infusion of glucagon or epinephrine alone resulted in a transient rise in glucose production (as measured by [3-(3)H]glucose). While glucagon infusion was accompanied by a rise in glucose clearance, with epinephrine there was a sustained, 20% fall in glucose clearance. When epinephrine was infused together with glucagon, the rise in glucose production was additive, albeit transient. However, the inhibitory effect of epinephrine on glucose clearance predominated, thereby accounting for the exaggerated glycemic response to combined infusion of glucagon and epinephrine. Although infusion of cortisol alone had no effect on glucose production, the addition of cortisol markedly accentuated hyperglycemia produced by glucagon and(or) epinephrine primarily by sustaining the increases in glucose production produced by these hormones. The combined hormonal infusions had no effect on beta-hydroxybutyrate concentration. It is concluded that (a) physiologic increments in glucagon, epinephrine, and cortisol interact synergistically in the normal dog so as to rapidly produce marked fasting hyperglycemia; (b) in this interaction, epinephrine enhances glucagon-stimulated glucose output and interferes with glucose uptake while cortisol sustains elevations in glucose production produced by epinephrine and glucagon; and (c) these data indicate that changes in glucose metabolism in circumstances in which several counterregulatory hormones are elevated (e.g., "stress hyperglycemia") are a consequence of synergistic interactions among these hormones.
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PMID:Synergistic interactions of physiologic increments of glucagon, epinephrine, and cortisol in the dog: a model for stress-induced hyperglycemia. 76 40

Extreme hyperinsulinism was observed in endotoxin-shock dogs made hyperglycemic by glucose infusion. Qualitatively (at least in terms of gel filtration characteristics), the insulin secreted under these conditions was normal. Hyperinsulinism was not observed in endotoxin-shock dogs not given glucose. Thus hyperinsulinism does not explain the hypoglycemia so frequently observed in endotoxin-treated dogs. Hyperinsulinsm could not be impaired degradation of insulin as disappearance of labeled insulin as well as cold insulin was comparable in control and endotoxin-treated animals. An adrenergic mechanism (either beta receptor stimulation or postadrenergic hyperresponsiveness of the beta cells) probably does not explain the hyperinsulinism observed in endotoxin-shock dogs given glucose as beta blockade failed to inhibit the hyperinsulinsm. Hyperinsulinism was not observed in endotoxin-shock dogs given tolbuamide. A tenfold rise in plasma IRG was observed in endotoxin-treated dogs whether glucose was infused or not. The persistently low IRI levels in endotoxin-treated dogs not given glucose suggest that hyperresponsiveness of the beta cell to glucagon was not present in these animals. Extreme hyperinsulinsm in response to induced hyperglycemia in endotoxin-shock dogs is unexplained. Hyperresponsiveness of the beta cell to glucose during endotoxin shock seems likely.
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PMID:Hyperinsulinism in endotoxin shock dogs. 77 54

To examine whether abnormal pancreatic alpha-cell function found in human diabetes mellitus may represent a selective insensitivity to glucose, plasma glucagon responses to hyperglycemia and elevation of plasma free fatty acid levels (both known suppressors of glucagon secretion) were compared in juvenile-onset, insulin-requiring diabetic subjects, and in normal nondiabetic subjects. In the latter, both elevation of plasma free fatty acid levels induced by heparin administration of hyperglycemia produced by intravenous infusion of glucose resulted in a comparable 30--40% suppression of circulating glucagon levels (P less than 0.01). In the diabetic subjects, glucagon suppression by hyperglycemia (less than 20%) was less than that occurring in normal subjects (P less than 0.01), even when accompanied by infusion of supraphysiologic amounts of insulin. However, suppression of glucagon levels by elevation of plasma free fatty acids in the diabetic group was similar to that found in normal subjects and of comparable magnitude to that due to hyperglycemia in the normal subjects. These results thus demonstrate a selective impairment of the diabetic alpha-cell response to glucose and provide further evidence for the presence of an abnormal alpha-cell glucoreceptor in human diabetes mellitus.
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PMID:Comparison of the suppressive effects of elevated plasma glucose and free fatty acid levels on glucagon secretion in normal and insulin-dependent diabetic subjects. Evidence for selective alpha-cell insensitivity to glucose in diabetes mellitus. 78 98

Glucagon is secreted not only by A2-cells of the pancreatic islets but also by A cells in the gastric fundus and duodenum. Several reports have demonstrated that the glucagon plasma concentration is increased in genetic diabetes as well as in many conditions associated with a decreased glucose tolerance such as hepatic cirrhosis, myocardial infarction, infectious diseases, burns, taumatic shock, glucagonomas, acute pancreatitis, acromegaly, pheochromacytoma and Cushing's syndrome. Hyperglucagonemia is particularly important in diabetic ketoacidosis and in non-ketotic hyperosmolar coma. The mechanisms responsible for the diabetic's hyperglucagonemia remain controversial. According to several authors, the increased glucagon secretion is, for its main part, secondary to a prolonged defect in insulin secretion and thus relatively insensitive to an acute insulin administration. According to others, the A cell abnormality is of primary origin, independant from insulin deficiency and its effects are cumulative with those of the insulin lack. Several reports dealing with induced or spontaneous experimental diabetes are in favor of the first or the second hypothesis. It appears likely that glucagon plays a role in the metabolic derangments of diabetes. Indeed, hepatic glucose production is closely related to the ratio of molar concentrations of insulin and glucagon. Finally, in insulin-dependant diabetics, somatostatin infusion reduces plasma glucagon concentration and blood glucose and prevents the development of ketosis after withdrawal of insulin therapy. These results illustrate the contribution of glucagon in the pathogenesis of hyperglycemia and ketosis. Several arguments have been accumulated in favor of the following concept: diabetes hyperglycemia results both from glucose under-utilization secondary to insulin lack and from hepatic glucose over-production due to glucagon excess. Although controversial, the role of glucagon in ketogenesis appears likely.
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PMID:[The role of glucagon in hyperglycemia. A review (author's transl)]. 79 28

An extra-corporeal blood circuit was established between the cranial pancreatico-duodenal vein and the portal vein in the dog. Timed measurements of flow, hematocrit, insulin and glucagon concentrations in this circuit were made in order to calculate the secretion rates of insulin and glucagon. The plasma glucose concentration in the pancreatico-duodenal vein was monitored at steady state from 50 to 330 mg/100 ml for periods of 70 min by infusing a saline solution or glucose into the cranio-pancreatico-duodenal artery. No change in peripheral glucose concentrations was detected. 1. When glucose concentration in the PD vein was lowered from 100 mg/100 ml to about 50 mg/100 ml, the basal insulin secretion rate was not modified. When the glucose concentration was increased from 100 mg/100 ml to about 300 mg/100 ml, the insulin secretion rate increased linearly over the range of concentrations tested. 2. Glucagon secretion rate was unmodified throughout the range of glycemia tested. Whereas net pancreatic glucagon secretion rate was not reduced by selective pancreatic hyperglycemia, it was reduced by systemic hyperglycemia at about the same concentration. 3. In atropinized pancreas, low frequency (2 Hz) electrical stimulation of the distal end of the ligated mixed pancreatic nerve caused a mean decrease of 44% in the secretion rate of insulin, and a mean increase of 42% in the secretion rate of glucagon at all PD vein glucose concentrations studied. 4. It can be concluded, therefore, that the sympathetic nervous input at physiological frequencies controls the moment-to-moment secretory activity of the A and B cells of the pancreas independently of the concentrations of glucose.
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PMID:Control of A and B cells in vivo by sympathetic nervous input and selective hyper or hypoglycemia in dog pancreas. 79 26

On the basis of the blood glucose increase during the capitivity sand rats born in the desert were classified as normals, protodiabetics and diabetics, indicating a different adaptation to the new environment within a definite period. Isolated islets of animals, which did not develop a hyperglycemia, enhanced their insulin content during the adaptation period. The absolute insulin secretion rates in response to 16.5 mM glucose were rather similar between the three investigated groups and not modified by the insulin as well as glucagon content of pancreatic islets. But, since islets of hyperglycemic sand rats could not increase the insulin content, a significantly enhanced fractional secretion (as % of the content) could be observed. The results let us assume that the B-cell reaction during the adaptation period can be modified by further factors additionally to the changed environment.
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PMID:Pancreatic B-cell behaviour after changing the natural environment of sand rats (Psammomys obesus. 79 42


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