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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 various doses of insulin (25-, 50-, and 150 U/kg body weight) on the blood glucose level and islet-cytology of the frog Rana tigrina was studied until 96 h. Following the hormonal administration the frogs exhibited hypoglycemia, abnormal neuromuscular activity and degranulation of both the insulin secreting beta- and glucagon secreting alpha-(alpha2-) cells of the pancreatic islets. The action of insulin was dose and temperature dependent; the higher the dose and temperature, the greater the hypoglycemia and atrophy of islet tissue. The insulin-induced convulsive activity appears to be due to the direct action of this hormone on the nervous system; the shocks are not influenced by thermal variation. The great sensitivity of Rana tigrina to exogenous insulin seems to be related to only a few alpha2-cells in the endocrine pancreas and consequently, a smaller amount of circulating glucagon in this animal.
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PMID:Insulin administration in the frog Rana tigrina: studies on the blood glucose and the histology of the endocrine pancreas. 36 39

The regulation of hepatic glucose production by glucagon and insulin has been studied in the intact dog. An attempt has been made to evaluate the role of basal physiological concentrations of the hormones in the regulation of glycogenolysis and gluconeogenesis. Somatostatin was infused continuously into postabsorptive dogs to inhibit the secretion of both glucagon and insulin. Either or both hormones were then replaced intraportally by continuous infusion as desired. The main observations were as follows. (1) When both hormones were simultaneously replaced for periods up to 4.5h, plasma insulin and glucagon concentrations, total glucose output (glycogenolysis plus gluconeogenesis), glucose utilization and the plasma glucose concentration closely matched the same parameters in 0.9% NaCl-infused controls. (2) When glucagon alone was infused, thereby creating a selective insulin deficiency, glucose output (primarily glycogenolysis) rapidly increased by as much as threefold. Glycogenolytic glucose production then fell off progressively and returned to the control value within 4h. The gluconeogenic conversion of [14C]alanine and [14C]lactate into [14C]glucose was stimulated markedly and increased progressively throughout the test period. Glucagon therefore converted the liver from an organ largely dependent on glycogenolysis for glucose production to one heavily dependent on gluconeogenesis. The potent inhibitory effect of basal insulin on postabsorptive glucose output was also clearly apparent. (3) When insulin alone was infused, thereby creating a selective glucagon deficiency, glucose output (glycogenolysis) fell abruptly by about 30% and remained decreased. Gluconeogenesis also decreased (20%) after the selective removal of both insulin and glucagon, but it only remained suppressed for 1h. The low glucose output led to a modest fall in the blood glucose concentration. Thus glucagon plays an important role in maintaining basal glucose production. (4) When insulin was infused and the plasma glucose was kept at its control concentration by infusion of glucose in similar experiments to the above, the hepatic output of glucose fell by as much as 75%. This demonstrates the presence of a glucagon-independent metabolic reflex triggered by a low plasma glucose concentration, the purpose of which is to maintain glucose output at a rate capable of preventing castastrophic hypoglycaemia.
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PMID:Control of hepatic glucose output by glucagon and insulin in the intact dog. 37 68

The present status of knowledge about glucagon pathophysiology in diabetes is reviewed. 1) A-cells behave abnormally in all varieties of diabetes mellitus, spontaneous and experimental, except perhaps in case of pancreatectomized humans. These abnormalities are : hyperreactivity of A-cells to arginine, non suppressibility by glucose, and absence of stimulation following hypoglycemia. 2) These abnormalities appear as secondary in most instances : a) A-cells behave in a normal way in most studies with prediabetics ; b) plasma glucagon concentration is normalized by excellent control of diabetes or following prolonged insulin infusion. High doses of insulin are required most of the times to obtain a normalization of A-cell function : in insulin-dependent diabetics, the physiological portoperipheral insulin gradient no longer exists, and the high doses of insulin which are necessary may be the only mean to reconstitute the high insulin concentrations supposed to be present at the A-cell level. 3) Conflicting results have been collected about the role of this glucagon excess in aggravating the diabetic metabolic syndrome. Evanescent effects follow sustained glucagon infusions: but in diabetics, glucagon bursts rather than permanent hyperglucagonemia are observed and these appear deleterious to glucose tolerance. It seems clear however that insulin deprivation is required for the full expression of the consequences of glucagon excess.
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PMID:Glucagon and diabetes mellitus. 37 65

Severe neonatal hypoglycemia with pathologic findings of diffuse nesidoblastosis of the pancreas is described in five children of both sexes from two families with unaffected parents. This appears to represent an autosomal recessive disorder of pancreatic development. Despite extensive testing, the diagnosis of hyperinsulinism was difficult in the index case of each family and delayed definitive treatment. Medical therapy with steroids and diazoxide was unsuccessful; pancreatectomy was required to treat persistent hypoglycemia. An abnormality of circulating glucagon found in one child with this disorder suggested that hyperinsulinism may not be the sole hormonal imbalance present, but rather that this disease is one of generalized disturbance of islet cell function. The history of severe, persistent neonatal hypoglycemia in an older sibling should lead the physician to investigate subsequent children for the presence of asymptomatic hypoglycemia.
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PMID:Familial nesidioblastosis: severe neonatal hypoglycemia in two families. 38 29

Ketonemia can be a physiological response to a reduction in dietary intake. It also may occur when energy demands exceed the energy intake. Normally, alimentary ketogenesis is the major source of ketone bodies in ruminants. During ketonemia there is increased hepatic ketone body production. During physiological ketosis, the mobilization of free fatty acids is inadequate to support a high rate of hepatic ketogenesis. However, during clinical ketosis, the hormonal status (low insulin, high glucagon/insulin ratio) in combination with hypoglycemia promotes excessive lipid mobilization and a greater hepatic removal of fatty acids and switches the liver to a higher rate of ketogenesis. The low insulin, furthermore, can impair maximal ketone body utilization, thus exacerbating the hyperketonemia.
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PMID:Roles for insulin and glucagon in the development of ruminant ketosis -- a review. 38 36

Six normal subjects and six normotensive insulin-dependent diabetics underwent two insulin hypoglycaemia tests after administration for three days of either a placebo or of acebutolol--a cardioselective beta-blocker--at a dose of 400 mg per day. The order in which the tests were performed was decided by random selection. Acebutolol suppressed the tachycardia which occurred as a reaction to hypoglycaemia but did not interfere with other warning symptoms and signs. In both normal subjects and diabetics, acebutolol neither worsened the initial hypoglycaemia nor did it delay a return to normal values. The increase in lactate levels following hypoglycaemia was not reduced by acebutolol but free fatty acid rebound was suppressed. Hormonal responses (glucagon, cortisol, growth hormone) were unaffected by the beta-blocker. If they are confirmed by long term studies, these results would suggest that acebutolol is safer to use than non-cardioselective beta-blockers in the treatment of coronary insufficiency and of hypertension in diabetics exposed to the risk of hypoglycaemia.
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PMID:[The effects of acebutolol on endocrine and metabolic reactions induced by acute hypoglycaemia. Study in normal subjects and in insulin-dependent diabetics (author's transl)]. 39 44

A case of carcinoma of the stomach associated with severe hypoglycemia is reported. Diagnosis of insulinoma was excluded on the basis of history as well as laboratory tests. Postmortem examination revealed widespread small metastases to various organs; no metastasis was found in the pancreas; the histology of this gland did not show any pathological finding. No impairment in pituitary, thyroid, adrenal and liver function was detected. Fasting blood sugar ranged from 18 to 56 mg/100 ml. An oral glucose tolerance test showed a diabetic pattern with low insulin. Tolbutamide, glucagon and glucose injected i.v. gave only a moderate rise in plasma insulin levels; plasma glucagon response to arginine was subnormal. The determination of NSILA-s and gastrin in the serum of this patient gave normal values. Diazoxide infusion induced an increase in blood glucose and subsequent treatment with diazoxide relieved hypoglycemia for some months. The occasional detection of an islet cell antibody by immunofluorescence in this case is not easily understandable, but it might partly account for the carbohydrate intolerance. An impairment in gluconeogenesis dependent upon some substrate deficiency might account for the hypoglycemia in this patient.
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PMID:Gastric carcinoma associated with severe hypoglycemia sensitive to diazoxide. 39 98

The influence of a short-term treatment with acetylsalicylic acid (ASA 3,2 g/daily), an inhibitor of endogenous prostaglandin synthesis, on plasma glucose, glucagon and growth hormone responses to insulin-induced hypoglycemia, has been investigated in seven subjects. ASA caused a slight but significant reduction in basal glucose levels, but did not alter the pattern of glucagon and growth hormone secretion following hypoglycemia. On the basis of these results, it is hypothesized that endogenous prostaglandins are not implicated in the response of pancreatic alfa-cell to hypoglycemia.
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PMID:[Acetylsalicylic acid and hormonal response in insulin induced hypoglycemia]. 39 50

Hypoglycemia is known to stimulate human pancreatic polypeptide (hPP) secretion. To explore further the relationship between glucose availability and hPP release, we have examined the effect of tissue glucopenia induced by 2-deoxy-D-glucose (2-DG) on hPP plasma levels in normal subjects. As this glucose analogue activates the autonomic nervous system, we have also studied the influence of prior atropinization upon the hPP response to 2-DG. Moreover, we have tested the effects of iv epinephrine and norepinephrine on plasma hPP concentrations. Circulating glucagon was also measured. After the iv infusion of 2-DG (50 mg/kg), plasma hPP increased steeply from a fasting value of 104 +/- 24 pg/ml (SEM) to a peak of 2175 +/- 639 pg/ml at 45 min (P less than 0.01) and remained significantly elevated throughout the test. In contrast, prior injection of atropine (1 mg iv) lowered basal hPP levels and reduced conspicuously the hPP response to 2-DG. Epinephrine administration (6 micrograms/min for 60 min) did not significantly modify plasma hPP concentrations. However, 2 h after epinephrine withdrawal, circulating hPP showed a brisk elevation coinciding with the decline of glycemia to subbaseline values. During norepinephrine infusion (6 micrograms/min for 60 min), only a minor and transient increase of plasma hPP was found. Plasma glucagon rose significantly after 2-DG infusion, but this response was virtually absent in the atropine experiment. Whereas the well known glucagon tropic activity of epinephrine was evidenced, norepinephrine failed to exert an obvious effect on glucagonemia. Our data demonstrate that 2-DG induces a powerful stimulation of hPP secretion in normal subjects and suggest that this action is mediated in part, if not entirely, by the parasympathetic nervous system. On the other hand, a major role of the sympathoadrenal system in response of hPP to 2-DG or to hypoglycemia does not seem probable. Finally, the hyperglucagonemic effect of 2-DG seems also to be dependent on cholinergic transmission.
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PMID:Stimulation of pancreatic polypeptide and glucagon secretion by 2-deoxy-D-glucose in man: evidence for cholinergic mediation. 40 Jul 18

The direct effect of insulin on the secretion of insulin (as measured by C-peptide), glucagon, gastric inhibitory polypeptide, and gastrin was studied in normal subjects by infusing insulin while the plasma level of glucose was maintained in the normal fasting range (euglycemic clamp). Insulin-induced hypoglycemia resulted in increases in circulating glucagon and gastric inhibitory polypeptide, a decrease in C-peptide, and no change in gastrin levels. In contrast, during the euglycemic clamp, insulin was found to behave a direct suppressive effect on the secretion of glucagon, C-peptide, and gastrin, but no effect on levels of gastric inhibitory polypeptide.
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PMID:Direct effect of insulin on secretion of insulin, glucagon, gastric inhibitory polypeptide, and gastrin during maintenance of normoglycemia. 40 Jul 22


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