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)

The effect of mammalian crystalline glucagon (0.5 mg and 2.0 mg/kg) on the blood glucose level and pancreatic islets of Rana tigrina was studied at different stages after its treatment. This frog is moderately sensitive to glucagon and exhibits hyperglycemia and regressive changes, primarily in the beta- and secondarily in the alpha-cells of the islet tissue. The effectiveness of the hormone depends upon the dose employed. The restricted damage in only a fraction of the alpha-cells indicates that this fraction is like the glucagon secreting alpha2-cells of mammals and is the source of glucagon in Rana tigrina also.
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PMID:Histophysiology of the pancreatic islets of Rana tigrina, treated with glucagon. 80 7

The prevalence of diabetes due to chronic pancreatitis would appear to be increasing. In western countries this is associated with the known increase in alcohol consumption and AIP. Malnutrition may be etiologic in tropical areas. The incidence of diabetes in chronic pancreatitis is dependent on a number of factors. It is more common in alcohol-induced pancreatitis, rarely occurs after the first attack but tends to increase with time and rises markedly in calcific pancreatitis. Abnormal glucose tolerance occurred in 91% of patients with calcific pancreatitis and 70% of patients with noncalific AIP in our follow up of five to 12 years. This stresses the importance of serial regular glucose tolerance tests in these patients (Table I). The insulin-reserve is severely depleted in most patients who do not yet demonstrate abnormal glucose tolerance, indicating that pancreatitis regularly affects the islets and that nearly all patients are potential diabetics. The beta cells appear to respond better to oral glucose, glucagon or secretin than to i.v. glucose suggesting a selective glucose receptor loss or block to hyperglycemia in chronic pancreatitis. The alpha cells seem to be more resistant to the effects of chronic pancreatitis but true hypoglucagonemia was found in 16% of patients. In addition, stimulated growth hormone secretion may be deficient in pancreatic diabetes. These last two factors, among others, may be responsible for the protracted and even fatal hypoglycemia to which some patients with AIP on insulin therapy are liable. The danger of drug-induced hypoglycemia, coupled with the infrequency of vasculopathy, retinopathy and nephropathy in pancreatic diabetes has induced us to keep these patients hyperglycemic and glycosuric rather than in a sugar-free state, as long as symptoms are contained. Recurrent abdominal pain, marked weight loss and associated steatorrhea often raise special problems in the management of the pancreatic diabetic.
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PMID:Clinical and hormonal aspects of pancreatic diabetes. 80 21

To study the individual effects of glucagon and growth hormone on human carbohydrate and lipid metabolism, endogenous secretion of both hormones was simultaneously suppressed with somatostatin and physiologic circulating levels of one or the other hormone were reproduced by exogenous infusion. The interaction of these hormones with insulin was evaluated by performing these studies in juvenile-onset, insulin-deficient diabetic subjects both during infusion of insulin and after its withdrawal. Infusion of glucagon (1 ng/kg-min) during suppression of its endogenous secretion with somatostatin produced circulating hormone levels of approximately 200 pg/ml. When glucagon was infused along with insulin, plasma glucose levels rose from 94 +/- 8 to 126 +/- 12 mg/100 ml over 1 h (P less than 0.01); growth hormone, beta-hydroxy-butyrate, alanine, FFA, and glycerol levels did not change. When insulin was withdrawn, plasma glucose, beta-hydroxybutyrate, FFA, and glycerol all rose to higher levels (P less than 0.01) than those observed under similar conditions when somatostatin alone had been infused to suppress glucagon secretion. Thus, under appropriate conditions, physiologic levels of glucagon can stimulate lipolysis and cause hyperketonemia and hyperglycemia in man; insulin antagonizes the lipolytic and ketogenic effects of glucagon more effectively than the hyperglycemic effect. Infusion of growth hormone (1 mug/kg-h) during suppression of its endogenous secretion with somastostatin produced circulating hormone levels of approximately 6 ng/ml. When growth hormone was administered along with insulin, no effects were observed. After insulin was withdrawn, plasma beta-hydroxybutyrate, glycerol, and FFA all rose to higher levels (P less than 0.01) than those observed during infusion of somatostatin alone when growth hormone secretion was suppressed; no difference in plasma glucose, alanine, and glucagon levels was evident. Thus, under appropriate conditions, physiologic levels of growth hormone can augment lipolysis and ketonemia in man, but these actions are ordinarily not apparent in the presence of physiologic levels of insulin.
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PMID:Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin. 82 Jul 17

In 51 surgical intensive-care patients, who were given 400 to 650 g glucose per day i.v., 18% of arterial blood sugar values were found to be above 250 mg/100 m1 in spite of frequent insulin administration. In 8 lobectomized patients increased plasma levels of pancreatic glucagon, cortisol, and growth hormone were observed which may in part explain postoperative glucose intolerance. In addition previous carbohydrate deprivation was found to impair glucose tolerance. Several measures are suggested to reduce the incidence of hyperglycemia during i.v. glucose feeding. In a further study 24 cholecystectomized or vagotomized patients received in alternate sequence either a combination of glucose (G), fructose (F) and xylitol (X), the G/F/X-ratio being 1/2/1, or glucose alone for 5 days. The infusion rate was 1.42 g carbohydrate/kg/24 hrs. On operation day and was increased by the same amount every day up to 7.14 g/kg/24 hrs. Tolerance was good in both groups but urinary losses of infused substrates were higher in the group receiving the GFX-combination. It is concluded that after surgery of intermediate magnitude the GFX-combination offers no advantage over glucose alone. However, in severely ill patients, where glucose intolerance is more pronounced, further carefully monitored studies with sugar substitutes appear of interest.
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PMID:Postoperative tolerance to glucose and sugar substitutes. 82 90

Long term reversal of alloxan diabetes has been accomplished by intraperitoneal isotransplantation of enzymatically dispersed neonatal pancreas. In contrast, allotransplanted recipients showed only a transient recovery from the alloxan diabetes followed by a return to the diabetic state at the time of the homograft rejection. These data strongly suggest that the reversal of the diabetic state was a consequence of the transplanted islets. This conclusion is further supported by quantitative analysis of biopsied pancreases from successfully reversed recipients which reveals only 3% of the normal beta cell mass. By comparison, recovery of transplanted islets composed primarily of aldehyde fuchsin positive beta cells was routinely accomplished in these recipients. Utilization of the more specific unlabeled immunoperoxidase method has revealed that some of the transplanted islets are composed of cells positive for glucagon and somatostatin, as well as insulin. Other recovered transplanted islets (generally smaller in size) are composed primarily of one cell type or the other. The presence of insulin, glucagon, somatostatin, and delete pancreatic polypeptide positive cells in the islets of normal rat pancreas has been confirmed. In addition, cells reacting positively for these hormones have been observed in the alloxan diabetic rat pancreatic islets and in islets from reversed recipients. The time required for the disappearance of glycosuria and hyperglycemia (usually occurring from one to eleven weeks posttransplantation) appeared to be related to the amount and age of the donor islet tissue transplanted. Fetal islet tissue was more effective on a per milligram basis in reversing the diabetic state. In addition, while reversal was obtained by transplantation of as little as 5 mg of neonatal islet tissue, relatively large amounts (20 mg) were required before successfully reversed recipients responded normally to glucose tolerance test. By comparison, a similar reversal of diabetes with normal response to glucose load was attained by transplanting only 3 mg of fetal islet tissue. Quantitative morphological evidence of large increases in absolute islet mass, obtained in fetal transplants at the renal subcapsular site suggests that the superiority of fetal islet donor tissue may by in its high growth potential. No adverse effects of an in vitro organ culture period, prior to transplantation, were observed with regard to the ability of neonatal tissue to reverse the diabetic state or for fetal islet tissue to continue to survive at the renal subcapsular site. Likewise, no advantage in regard to amelioration of the homograft rejection response was observed in cultured islet tissue; allotransplants of which were rejected at the kidney site.
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PMID:Transplantation of islet tissue in the rat. 82 63

A hypotensive, gut-contracting peptide neurotensin (NT), recently isolated from bovine hypothalami, has been found to produce hyperglycemia within minutes after iv injection into anesthetized rats. The dose-response relationship (deltaglucose, 15 min after injection) was linear over the range 30-200 pmol/100 g BW. NT did not alter the disappearance rate of [14C]glucose from plasma during the development of the hyperglycemia. However, the peptide caused a fall in liver glycogen (52 +/- 6.5 to 41 +/- 3.3 mg/g) and a 7-fold increase in the activity of the 5'-AMP independent form of liver glycogen phosphorylase. Activation of liver glycogen phosphorylase did not occur in vitro under conditions found suitable for demonstrating the effectiveness of glucagon, suggesting the possible involvement of an intermediary substanc(s) in vivo. Acute adrenalectomy did not prevent the response. Hypophysectomized rats (4 days post-operative) were less sensitive to NT, perhaps as a consequence of their diminished liver glycogen levels (normal, 52 +/- 6.5 mg/g; hypophysectomized, 23 +/- 1.8 mg/g); however, the presence of the pituitary was not essential for this response. NT was also effective in rats with hereditary diabetes insipidus (Brattleboro strain). At the time intervals sampled, radioimmunoassayable plasma levels of growth hormone, glucagon, and insulin were not significantly changed after injection of NT into normal rats. Pretreatment of rats with reserpine (7 mg/kg), morphine sulfate (10 mg/kg), propranolol (5mg/kg), or phenoxybenzamine (10 mg/kg) did not prevent the response. These findings characterize the action of NT on liver glycogen metabolism and blood glucose levels, but a physiological role for NT in this regard remains to be demonstrated.
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PMID:Hyperglycemic effect of neurotensin, a hypothalamic peptide. 82 91

The responses of glucagon, growth hormone, and insulin secretion to the oral administration of glucose and to the intravenous infusion of saline, arginine, and insulin were measured in seven patients who had stable diabetes, eight who had unstable diabetes, and seven healthy volunteers. Hyperglycemia suppressed secretion of glucagon in normal subjects but not in diabetics. The oral glucose and arginine infusion tests demonstrated partial preservation of insulin-secretory ability in stable diabetics and its virxual absence in unstable diabetics. Glucagon responses to arginine infusion were similar in all three groups. In response to hypoglycemia induced by insulin infusion, the concentrations of plasma glucagon increased in normal subjects and, to a lesser extent, in stable diabetics but increased in only two of the unstable diabetics. The impairment in glucagon response during hypoglycemia in diabetics correlated positively with the degree of diabetic instability and insulin deficiency during glucose and arginine testing. The severity of the insulin deficiency also correlated with the degree of diabetic instability. These findings support the hypothesis that inherent abnormalities of insulin and glucagon secretion may account for many of the clinical characteristics of unstable and stable diabetic patients.
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PMID:Abnormalities of endogenous glucagon and insulin in unstable diabetes. 83 May 63

Glucose-glucagon relationships were examined in adult sheep. Hyperglycemia was induced by infusing glucose at 120 mg/hr/kg body weight. Hypoglycemia was obtained by infusing insulin at 1.2 U/hr. In several experiments glucose at 40 mg/hr/kg was infused with insulin to obtain hyperinsulinemia without hypoglycemia to distinguish glucose-insulin effects. Glucagon concentrations decreased during hyperglycemia and increased during hypoglycemia. This study indicates that glucose-glucagon interactions may be important in regulation of glucagon secretion in sheep.
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PMID:Glucose-glucagon relationships in adult sheep. 83 95

The suppressibility of plasma glucagon concentrations by glucose was investigated in normal and diabetic children. Fasting concentrations of plasma glucagon were similar in normal and in diabetic children despite the hyperglycemia of the latter. Infusion of glucose promptly suppressed glucagon values in the normal as well as in the diabetic children pretreated with half of their usual morning dose of insulin. Glucose alone, however, did not suppress plasma glucagon in diabetic patients, despite the attainment of significant hyperglycemia. Administration of insulin during an ongoing glucose infusion in the diabetic patients lowered their blood glucose concentration; the concentration of glucagon rose transiently when the glucose concentration fell. These data confirm the existence of relative hyperglucagonemia inappropriate for the degree of blood glucose concentration in diabetic children deprived of insulin. The data also suggest that this hyperglucagonemia is secondary to insulin deficiency and suppressibility of glucagon by glucose can be restored by insulin therapy.
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PMID:Suppressibility of glucagon secretion by glucose in juvenile diabetes. 83 65

A system consisting of an isolated dog stomach perfused with whole blood has been designed to study gastric glucagon secretion. Under basal conditions, gastric glucagon release was 0.0-3.1 ng glucagon/100g of stomach per min. Arginine, at an arterial plasma concentration averaging 10 mM, elicited a rapid glucagon release. This gastric glucagon release was almost completely abolished by somatostatin (100 ng/ml). The release of gastric glucagon was not affected by hyperglycemia alone but was reduced by about 40% when hyperglycemia was concomitant with an hyperinsulinemia within the physiological range. These observations support the concept that adequate concentrations of insulin are necessary in order for hyperglycemia to inhibit gastric glucagon secretion. Furthermore, it is suggested that the isolated perfused dog stomach might provide a unique tool permitting investigation of alpha-cell function in the absence of endogenously released insulin.
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PMID:Factors controlling gastric-glucagon release. 84 58


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