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 direct effects of porcine insulin and glucagon on bone collagen and non-collagen protein synthesis have been examined in cultures of calvaria obtained from 21-day fetal rats. Bones were incubated for 24 to 96 h and [3H]proline was added for the last 2 h of culture. Incorporation of the label into collagenase-digestible protein (CDP) and noncollagen protein (NCP) was determined using purified bacterial collagenase. Insulin increased the labeling of CDP by 60 to 115% at concentrations of 10(-9) to 10(-6) M. A smaller stimulatory effect was observed on NCP. The effect on CDP appeared after 12 to 24 h of culture, was maintained for 96 h in the continuous presence of the hormone, but was lost within 3 h of removal of insulin from the culture medium. Insulin appeared to have a direct effect on collagen synthesis and not on collagen breakdown. Insulin did not affect the incorporation of [3H]uridine or [3H]thymidine into the RNA and DNA fractions of bone at 24 h. Insulin opposed the inhibitory effects of parathyroid hormone and dibutyryl cyclic-3',5'-adenosine monophosphate and to a lesser extent, the inhibitory effect of isobutylmethylxanthine on the labeling of CDP. Glucagon did not affect the response to insulin and by itself had small and variable inhibitory effects on proline incorporation.
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PMID:Hormonal control of bone collagen synthesis in vitro. Effects of insulin and glucagon. 40 59

The administration of cyproheptadine (25 mg/kg; i.p.) resulted in an increase of plasma insulin and glucagon (measured using 30 K antibody) 30, 60 and 120 min after injection to fasted rats. This dose of cyproheptadine also induced a hyperglycemia whereas a lower dose (5 mg/kg; i.p.), which did not alter plasma hormone levels, was associated with a hypoglycemia. Fed rats showed a reduction of plasma insulin with a similar elevation of blood glucose after cyproheptadine. Administration of an exogenous load of arginine resulted in increases of plasma insulin and glucagon of a greater magnitude than induced by cyproheptadine, however, cyproheptadine pretreatment (25 mg/kg) completely suppressed the pancreatic response to the amino acid, resulting in blood hormone levels similar to values seen after cyproheptadine administered alone. Cyproheptadine pretreatment also prevented the hyperinsulinemia and hypoglucagonemia resulting from glucose loading. alpha-Adrenergic receptor blockade (with phentolamine), beta adrenergic receptor blockade (with propranolol) and adrenodemedullation did not alter pancreatic responsiveness to the drug.
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PMID:Paradoxical short-term effects of cyproheptadine on insulin and glucagon release in the rat. 43 34

The effects of continuous infusions of insulin in physiologic doses on glucose kinetics and circulating counterregulatory hormones (epinephrine, norepinephrine, glucagon, cortisol, and growth hormone) were determined in normal subjects and diabetics. The normals received insulin at two dose levels (0.4 and 0.25 mU/kg per min) and the diabetics received the higher dose (0.4 mU/kg per min) only. In all three groups of studies, continuous infusion of insulin resulted in an initial decline in plasma glucose followed by stabilization after 60-180 min. In the normal subjects, with the higher insulin dose there was a fivefold rise in plasma insulin. Plasma glucose fell at a rate of 0.73+/-0.12 mg/min for 45 min and then stabilized at 55+/-3 mg/dl after 60 min. The initial decline in plasma glucose was a result of a rapid, 27% fall in glucose output and a 33% rise in glucose uptake. Subsequent stabilization was a result of a return of glucose output and uptake to basal levels. The rebound increment in glucose output was significant (P < 0.05) by 30 min after initiation of the insulin infusion and preceded, by 30-45 min, a significant rise in circulating counterregulatory hormones. With the lower insulin infusion dose, plasma insulin rose two- to threefold, plasma glucose initially fell at a rate of 0.37+/-0.04 mg/min for 75 min and stabilized at 67+/-3 mg/dl after 75 min. The changes in plasma glucose were entirely a result of a fall in glucose output and subsequent return to base line, whereas glucose uptake remained unchanged. Plasma levels of counterregulatory hormones showed no change from basal throughout the insulin infusion. In the diabetic group (plasma glucose levels 227+/-7 mg/dl in the basal state), the initial rate of decline in plasma glucose (1.01+/-0.15 mg/dl) and the plateau concentration of plasma glucose (59+/-5 mg/dl) were comparable to controls receiving the same insulin dose. However, the initial fall in plasma glucose was almost entirely a result of suppression of glucose output, which showed a twofold greater decline (60+/-6%) than in controls (27+/-5%, P <0.01) and remained suppressed throughout the insulin infusion. In contrast, the late stabilization in plasma glucose was a result of a fall in glucose uptake to values 50% below basal (P < 0.001) and 39% below that observed in controls at termination of the insulin infusion (P < 0.01). Plasma norepinephrine and glucagon failed to rise during the insulin infusion, whereas plasma epinephrine, cortisol, and growth hormone rose to values comparable to controls receiving the same insulin dose. It is concluded that (a) in normal and diabetic subjects, physiologic hyperinsulinemia results in an initial decline followed by stabilization of plasma glucose despite ongoing infusion of insulin; (b) in the normal subjects, a rebound increase in glucose output is the initial or principal mechanism counteracting the fall in plasma glucose and occurs (with an insulin dose of 0.25 mU/kg per min) in the absence of a rise in circulating counterregulatory hormones; (c) in diabetics, although the changes in plasma glucose are comparable to controls, the initial decline is a result of an exaggerated suppression of glucose output, whereas the stabilization of plasma glucose occurs primarily as a consequence of an exaggerated fall in glucose uptake; and (d) failure of plasma norepinephrine as well as glucagon to rise in the diabetics may contribute to the exaggerated suppression of glucose output.
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PMID:Influence of continuous physiologic hyperinsulinemia on glucose kinetics and counterregulatory hormones in normal and diabetic humans. 44 32

The effects of exogenous insulin upon the response of immunoreactive glucagon (IRG) to i.v. glucose were studied in diabetic and nondiabetic subjects. In nondiabetics, a rapid injection of 25 g of glucose lowered plasma IRG levels. In adult-onset diabetics, the glucose-induced decline in IRG was normal despite a subnormal glucose-induced insulin rise, in contrast to impaired IRG suppressibility previously reported when such patients received an oral glucose load. The magnitude of their glucose-induced IRG decline was not augmented by exogenous insulin, even when insulin levels were acutely raised above 300 micro units/ml. In juvenile-type diabetics, basal IRG levels were normal following overnight insulin infusion, but the glucose-induced IRG decline was only half that of the nondiabetics. However, it became normal when hyperinsulinemia was acutely produced by supplementary insulin. Thus, whenever insulin levels rise in response to an increase in hyperglycemia, as they do spontaneously in nondiabetics and in adult-type diabetics and as they do when juvenile diabetics are given supplementary insulin together with the glucose bolus, the decline in IRG in response to an i.v. glucose load is as great as in nondiabetics. The findings are compatible with the view that glucose-induced suppression of IRG may require a concomitant rise in insulin.
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PMID:Effects of insulin on the response of immunoreactive glucagon to an intravenous glucose load in human diabetes. 44 98

The response of gastric inhibitory polypeptide (GIP) levels to oral glucose in 11 insulin-dependent diabetics was compared to that in 8 age- and sex-matched healthy controls to determine whether they would show the pattern of GIP hypersecretion reported by other workers in maturity-onset, insulin-independent diabetes. One gram of glucose per kg bw resulted in a higher level of glycemia and a significantly diminished GIP response in diabetics when compared to controls (6,018 +/- 1,337 vs. 11,343 +/- 2,353 pg/ml.180 min min, respectively). There was virtually no beta cell response in the diabetics, as measured by changes in the levels of free insulin and connecting peptide. A significant lowering of glucagon levels occurred in the controls, while an inconsistent response was seen in the diabetics. An insulin infusion test was administered to test the hypothesis that insulin suppresses GIP secretion. Although hyperinsulinism, hypoglycemia, and suppression of endogenous insulin secretion were produced in the controls, no suppression of baseline GIP was detected. Similarly, hyperinsulinism and hypoglycemia failed to suppress baseline GIP levels in the diabetics. These results do not support a direct role for insulin in suppressing GIP in normal or diabetic subjects.
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PMID:Gastric inhibitory polypeptide response to hyper- and hypoglycemia in insulin-dependent diabetics. 45 45

Porphyria cutanea tarda (PCT) has a known increased incidence of diabetes mellitus and hepatic involvement. We investigated glucose tolerance and glucoregulatory hormone alterations in seven patients with PCT and correlated these results with hepatic histology by percutaneous liver biopsy. Abnormal glucose tolerance was observed in six of the seven patients (87%). Fasting serum insulin levels were normal range, and normal glucose and growth hormone responses to standard, exogenous intravenous insulin were observed. Fasting serum glucagon and urine free cortisol levels were normal in those patients in whom they were measured. While varying degrees of abnormalities were found on histopathologic exam of the liver biopsies, no patient met the criteria for cirrhosis, and none of the patients demonstrated abnormal levels of insulin counterregulatory hormones commonly seen in cirrhosis. Thus, liver disease may not be the sole cause of the observed glucose intolerance and hyperinsulinemia in PCT patients.
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PMID:Carbohydrate metabolism in porphyria cutanea tarda. 46 44

We have examined insulin and glucagon degrading activities of muscle and fat tissues in 11 subjects (4 lean controls, 3 insulin-resistant obese subjects, 2 non-insulin-dependent diabetic subjects, and 2 insulin-treated diabetic subjects) and correlated degrading activity with (1) basal insulin level and (2) state of insulin resistance. We found hyperinsulinemia and insulin resistance to be significantly correlated with accelerated insulin and glucagon degrading activity. Weight reduction in an insulin-resistant obese patients results in parallel reduction in both basal insulin level and insulin-glucagon degrading activity. These data are consistent with the hypothesis that an alternative mechanism for insulin resistance may be an accelerated insulin degradation at the level of target tissues.
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PMID:Accelerated insulin degradation: an alternate mechanism for insulin resistance. 51 Jan 40

The effect of glucagon and/or epinephrine on the response to physiologic insulin infusion was evaluated in dogs. Insulin alone produced a transient fall (50%) in glucose output, a threefold rise in glucose clearance, and a decline in plasma glucose, which then stabilized (40--45 mg/dl) afer 1 h. Glucagon infusion prevented the fall in glucose output, but had no effect on insulin-induced elevations in glucose clearance. The fall in plasma glucose was delayed (20 min), but late hypoglycemia was unaltered. Epinephrine infusion blocked the fall in glucose output as well as the insulin-induced rise in glucose clearance and uptake. Thus, while epinephrine and glucagon were equally effective in preventing the fall in glucose output induced by insulin, epinephrine was more effective in preventing insulin-induced hypoglycemia by virtue of its direct inhibitory action on insulin-stimulated glucose utilization. Simultaneous addition of glucagon and epinephrine increased glucose output twofold, suppressed glucose clearance, and caused a 15--30 mg/dl increase in plasma glucose despite ongoing hyperinsulinemia. Our data thus indicate that synergistic hormone interactions may play a role in the counterregulation of insulin hypoglycemia.
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PMID:Insulin antagonistic effects of epinephrine and glucagon in the dog. 51 45

The effect of glucagon on aspirin-induced damage to human gastric mucosa and its effect on gastric mucosal potential difference were studied in 27 healthy volunteers. Intragastric instillation of 600 mg of aspirin suspended in 100 ml of isotonic saline caused significant damage to 21 +/- 3% of surface epithelial cells and a marked reduction in gastric potential difference within 15 min of aspirin instillation. Glucagon, 2 mg given intravenously, caused hyperglucagonemia, hypophosphatemia, hyperinsulinemia, increased blood glucose levels and gastric pH, as well as significant prolonged elevation of gastric potential difference. Glucagon injection given 15 min before aspirin instillation effectively prevented surface epithelial cell damage, decreasing percentage of damaged cells to 3.5%. Glucagon did not prevent the drop in gastric potential difference evoked by aspirin, but did, however, prevent potential difference from falling below base line values after aspirin. This study showed in man that glucagon protects gastric mucosa against aspirin damage and suggests possible therapeutic value in clinical situations requiring prevention of aspirin-induced gastric mucosal damage.
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PMID:Effect of glucagon on aspirin-induced gastric mucosal damage in man. 62 Aug 96

Carbohydrate intolerance is a common abnormality in patients with chronic renal failure. In this group of patients we investigated the interrelation among glucose, insulin, and growth hormone and confirmed the presence of carbohydrate intolerance and hyperinsulinemia. In addition we demonstrated alterations in growth hormone regulation, characterized by (1) the lack of suppression of growth hormone by orally induced hyperglycemia and paradoxical increase in serum levels of growth hormone after the administration of intravenous glucose or glucagon; (2) lack of release of growth hormone with induced hypoglycemia and an exaggerated response to levodopa administration. Furthermore, thyrotrophin-releasing hormone stimulated growth hormone release, a phenomenon not observed in the control population. Our studies show an impaired hypothalamic regulation of growth hormones secretion in patients with renal failure undergoing long-term hemodialysis.
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PMID:Abnormalities in the regulation of growth hormone in chronic renal failure. 62 54


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