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)

This study was performed to investigate the role of pancreatic B-cell function on glucagon and somatostatin response to arginine. Isolated perfused rat pancreas was used for the experiment. Acute B-cell destruction was induced in vitro by 0.56 mM alloxan infused directly into the vascular system of the perfused pancreas. This resulted in a fall in basal insulin release and in a complete absence of hormone response to 20 mM arginine. Glucagon and somatostatin release during metabolic stimulus was superimposable on that observed in the control experiments (no alloxan infusion). We conclude that a normal B-cell function is not required for glucagon and somatostatin response to arginine.
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PMID:Pancreatic A- and D-cell response to arginine during acute alloxan-induced intra-islet insulinopenia. 289 95

When repeated epinephrine infusions are given to normal dogs as a partial stress model, there is exaggerated hyperglycaemia, associated with reduced plasma insulin levels and markedly decreased glucose clearance. In the present study, we have examined the hormonal and metabolic responses to two successive 60-min epinephrine (0.1 microgram . kg-1 . min-1) infusions with or without concomitant infusion of beta endorphin (0.3 microgram . kg-1 . min-1) in 6 alloxan-diabetic dogs. These studies have been compared to similar studies in 5 normal dogs. In the diabetic dogs, plasma glucose rose from 12.3 +/- 2.2 to 16.2 +/- 2.4 mmol/l (p less than 0.001) in response to the first epinephrine infusion and rose further to 18.1 +/- 2.5 mmol/l (p less than 0.001) during the second epinephrine infusion. The increases in plasma glucagon and glucose production were comparable with both infusions, but considerably greater than previously observed in normal dogs. In normal dogs, beta endorphin diminished the insulin response to the first epinephrine infusion (p less than 0.02), and abolished this response to the second (p less than 0.05). In addition beta endorphin also diminished the glucagon response to the second epinephrine infusion (p less than 0.01) and greatly potentiated epinephrine-induced suppression of glucose metabolic clearance during both infusions (p less than 0.001). However, beta endorphin did not appreciably alter the hyperglycaemic response to epinephrine due to a concomitant attenuation of the epinephrine-induced increase in hepatic glucose production. In contrast to normal dogs, beta endorphin did not modulate the effects of either the first or second epinephrine infusion on glucose kinetics in diabetic dogs. Also, beta endorphin failed to inhibit glucagon or insulin secretion in response to epinephrine in the diabetic animals. Since the alloxan-diabetic and normal dogs respond differently to the combined infusion of beta endorphin and epinephrine we conclude that the effects of beta endorphin observed in the normal dogs are dependent upon intact pancreatic endocrine function.
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PMID:Beta endorphin modulation of the glucoregulatory effects of repeated epinephrine infusion in alloxan-diabetic and normal dogs. 296 93

Alloxan diabetic dogs with insulin deficiency showed a transient but significant rise in glucagon levels after oral glucose load (1 g/kg). Pretreatment with atropine sulfate (0.2 mg/kg intravenously) totally suppressed this increase. So, the transient paradoxical rise of glucagon level observed in diabetic dogs after glucose intake is under cholinergic control.
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PMID:[Paradoxical hyperglucagonemia after oral administration of glucose in diabetic dogs. Impact of the cholinergic nervous system]. 297 Feb 86

The activities and zonal distribution of key enzymes of carbohydrate metabolism were studied in livers of diabetic rats. 48 h after alloxan treatment the following alterations were observed, intermediate values being reached after 24 h: Blood glucose, acetoacetate and beta-hydroxybutyrate were increased to more than 500%; liver glycogen was reduced to about 10%. Portal vein insulin was reduced to below 10%, portal glucagon was increased to almost 200%. The glucogenic enzymes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were enhanced to 320% and 150%, respectively. The glycolytic enzymes glucokinase and pyruvate kinase L (differentiated from the M2 isoenzyme with a specific anti-L-antibody) were lowered to 50% and 75%, respectively. The citrate cycle enzyme succinate dehydrogenase remained unchanged. The normal periportal to perivenous gradient of phosphoenolpyruvate carboxykinase of about 3:1, as measured in microdissected tissue samples, was enhanced to about 4:1 with activities elevated to 230% and 190%, respectively, in the two zones. The normal periportal to perivenous gradient of pyruvate kinase L of about 1:1.7, as determined with the microdissection technique, was reduced to about 1:1.4 with levels lowered to 55% and 45%, respectively, in the two zones. The even zonal distribution of pyruvate kinase M2 remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic zonation in liver of diabetic rats. Zonal distribution of phosphoenolpyruvate carboxykinase, pyruvate kinase, glucose-6-phosphatase and succinate dehydrogenase. 298 84

Hepatocytes from fasted, alloxan-diabetic rats were incubated in the absence of gluconeogenic substrates to deplete residual glycogen stores. Glucose production from lactate and pyruvate was enhanced in cells from diabetic rats relative to similarly treated hepatocytes from fasted, nondiabetic control rats. Gluconeogenesis from dihydroxyacetone, fructose, or glycerol was not increased but the formation of lactate plus pyruvate from dihydroxyacetone was decreased. The stimulation of gluconeogenesis by exogenous fatty acids was decreased by diabetes. The rates of gluconeogenesis in the presence of lactate plus pyruvate plus oleate were equal in hepatocytes from diabetic and control rats and indicate that the maximal rate of gluconeogenesis was not increased. With lactate plus pyruvate as substrates, stimulation of gluconeogenesis by norepinephrine or dibutyryl-cAMP was not altered by diabetes. The catecholamine stimulation of gluconeogenesis from glycerol also was unaffected. In contrast, diabetes decreased the maximal stimulation of gluconeogenesis from dihydroxyacetone by dibutyryl-cAMP, glucagon, or norepinephrine and this decrease was proportional to the decreased production of lactate plus pyruvate. The concentrations of glucagon or norepinephrine required for half-maximal stimulation were not altered by diabetes. Thus, the hormonal stimulation of gluconeogenesis from dihydroxyacetone is decreased by diabetes, probably because of decreased pyruvate kinase activity, but the interaction of glucagon and norepinephrine with hepatocytes and the subsequent stimulation of gluconeogenesis from physiologic substrates is not impaired.
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PMID:Regulation of gluconeogenesis in hepatocytes from fasted alloxan-diabetic rats. 299 Oct 49

Activities (mumol X min-1 X g liver) and zonal distributions of key enzymes of carbohydrate metabolism were studied in livers of streptozotocin-diabetic rats and compared to the values in alloxan-diabetes. Streptozotocin led to a non-ketotic diabetes with blood glucose being increased by more than fivefold but ketone bodies being in the normal range, while alloxan produced a ketotic diabetes with blood glucose, acetoacetate and beta-hydroxybutyrate being elevated by more than fivefold. Portal insulin was decreased to about 20% in streptozotocin- and more drastically to about 7% in alloxan-diabetes. Conversely, portal glucagon was increased in the two states to about 250% and 180%, respectively. The glucogenic key enzyme phosphoenolpyruvate carboxykinase (PEPCK) was enhanced in streptozotocin- and alloxan-diabetes to over 300%, while the glycolytic pyruvate kinase L (PKL) was lowered to 65% and 80%, respectively. The normal periportal to perivenous gradient of PEPCK of about 3:1, as measured in microdissected tissue samples, was maintained with elevated activities in the two zones. The normal periportal to perivenous gradient of PKL of 1:1.7 was diminished with lowered activities in the two zones. The glucogenic glucose-6-phosphatase (G6Pase) was increased in streptozotocin- and alloxan-diabetes to 130% and 140%, respectively, while the glucose utilizing glucokinase (GK) was decreased to 60% and 50%, respectively. The normal periportal to perivenous gradient of G6Pase, demonstrated histochemically, remained unaffected. Carnitine palmitoyltransferase (CPT) was increased to over 190% and acetyl-CoA carboxylase (ACC) was decreased to 60% in streptozotocin, non-ketotic diabetes, while the two enzymes were altered more drastically to 400% and 50%, respectively, in alloxan, ketotic diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gluconeogenic-glycolytic capacities and metabolic zonation in liver of rats with streptozotocin, non-ketotic as compared to alloxan, ketotic diabetes. 302 62

Alterations in content of glucose, insulin and glucagon in blood as well as binding of insulin with specific erythrocyte receptors were studied in 120 rats with alloxan diabetes and in intact animals. Content of insulin and glucagon was decreased in rat blood within 14 days of maintaining at high altitude, whereas glycemia developed only slightly. Binding of insulin with erythrocytes was increased more distinctly in control rats, which exhibited low index of this function at low altitude. Importance of this mechanism in activation of cellular glycolysis, an increase of 2,3-diphosphate glucose level in erythrocytes as a compensatory response to high altitude hypoxia are discussed.
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PMID:[The effect of altitude on insulin binding by erythrocytes in experimental alloxan diabetes]. 304 71

Changes in canine plasma glucose, immunoreactive glucagon (IRG), pancreatic polypeptide (PP) and insulin (IRI) were studied during the acute development of diabetes mellitus after iv alloxan injection. 100 mg or 75 mg/kg body weight of alloxan was injected iv and blood was taken successively till one or two days later. Plasma glucose showed four phases: first immediate and moderate decrease appeared 30 min after injection, second initial hyperglycemic phase, third hypoglycemic and fourth diabetic ones. Plasma IRI had already increased to 182 +/- 60 microU/ml 10 min after injection and again began to increase after about 6 h, peaking to 134 +/- 49 microU/ml at 18 h. Plasma IRG began increasing gradually soon after alloxan injection. The initial value was 196 +/- 26 pg/ml and it increased to 534 +/- 144 pg/ml at 4 h during the initial hyperglycemic phase, then reached a higher level through the hypoglycemic and diabetic phases. The change in plasma PP was similar to that in IRG. The initial value was 256 +/- 95 pg/ml at 12 h after injection, peaking to 840 +/- 100 pg/ml in the hypoglycemic phase. Similar blunted values were obtained following 75 mg/kg alloxan injection. Thus not only plasma IRI but also plasma IRG and PP varied greatly during the acute development of alloxan diabetes and some contribution of IRG to the initial hyperglycemic phase was suggested.
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PMID:Changes in plasma glucagon, pancreatic polypeptide and insulin during development of alloxan diabetes mellitus in dog. 305 65

The effects of sulfonylurea on glucagon secretion were characterized in the perfused rat pancreas using glibenclamide (1 microgram/ml) or tolazamide (10 micrograms/ml) in the presence of 3.3 mmol/l glucose. Glucagon release, which was unaffected by glibenclamide at 2.75 mmol/l calcium, was suppressed at 1.19 and 0.64 mmol/l but transiently stimulated at 0.25 mmol/l extracellular calcium. The insulinogenic effect of glibenclamide at 0.64 and 0.25 mmol/l calcium was enhanced by 35% and 89%, respectively, compared to the response at 2.75 mmol/l calcium. The stimulatory effect of the compound on somatostatin secretion, however, was lost at the lower calcium levels. The effects of tolazamide at 2.75 and 0.64 mmol/l calcium mimicked those of glibenclamide, thus indicating that our results with the latter compound may be representative for all sulfonylureas. In pancreata from insulin-deficient alloxan-diabetic rats, glibenclamide completely lost its inhibitory effect on glucagon release at 0.64 mmol/l calcium. Inhibition was not restored by adding insulin (25 U/l) to the perfusate. However, when diabetic rats had been treated with insulin for 6-7 days, glibenclamide suppressed glucagon release at low calcium levels in the absence of stimulated insulin and somatostatin release. It is concluded that, at low calcium concentrations, sulfonylureas suppress glucagon secretion by a direct action on the A cell and not through paracrine interactions by insulin and somatostatin. Prolonged insulin deficiency impairs the sulfonylurea action on glucagon secretion.
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PMID:Sulfonylurea-induced inhibition of glucagon secretion from the perfused rat pancreas: evidence for a direct, non-paracrine effect. 310 22

Insulin caused the inhibition of glucagon-stimulated adenylate cyclase activity in liver plasma membranes, but failed to inhibit this activity in liver membranes from rats made diabetic by treatment with either alloxan or streptozotocin. Treatment of streptozotocin-diabetic rats with insulin, to normalize their blood glucose concentrations, restored this action of insulin. Rats treated with the biguanide drug metformin exhibited a decreased content of the inhibitory guanine nucleotide regulatory protein Gi in liver plasma membranes assessed both structurally, by using a specific polyclonal antibody (AS7), and functionally. Treatment of normal rats with metformin did not alter insulin's ability to inhibit adenylate cyclase in liver plasma membranes; however, metformin treatment of streptozotocin-diabetic rats completely restored this inhibitory action of insulin. Liver plasma membranes from streptozotocin-diabetic animals which either had or had not been treated with metformin had contents of Gi which were less than 10% of those seen in control animals. We conclude that: (i) insulin does not inhibit adenylate cyclase activity through the inhibitory guanine nucleotide regulatory protein Gi; (ii) streptozotocin- and alloxan-induced diabetes elicit a selective insulin-resistant state; and (iii) metformin can exert a post-receptor effect, at the level of the liver plasma membrane, which restores the ability of insulin to inhibit adenylate cyclase.
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PMID:Treatment of streptozotocin-diabetic rats with metformin restores the ability of insulin to inhibit adenylate cyclase activity and demonstrates that insulin does not exert this action through the inhibitory guanine nucleotide regulatory protein Gi. 312 29


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