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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxin from the scorpion Leiurus quinquestriatus was used to release norepinephrine from sympathetic nerve endings in the perfused rat pancrease. Addition of toxin, 10 mug./ml., to perfusate containing 0.3 mg./ml. glucose caused a large increase in release of norepinephrine and glucagon. Glucagon secretion was suppressed by perfusate containing 3.0 mg./ml. glucose but still responded to stimulation with scorpion toxin. Atropine, 10 muM, had no effect on either norepinephrine or glucagon release in response to scorpion toxin. The release of glucagon was blocked by 100 muM propranolol, 10 muM phentolamine, or 30 muM phenoxybenzamine. Somatostatin, 55nM, did not affect the release of norepinephrine by scorpion toxin but totally inhibited the glucagon response. These results suggest that pharmacologic stimulation of the adrenergic nerve endings in the rat pancreas can elicit a rapid release of glucagon. This response can be prevented by appropriate concentrations of either alpha or beta adrenergic blocking agents or somatostatin.
Diabetes 1976 Aug
PMID:Stimulation of glucagon secretion by scorpion toxin in the perfused rat pancreas. 78 80

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

Eighteen diabetic patients with lactic acidosis (L.A.) were analyzed for possible causal factors, metabolic changes, and efficacy of treatment. An antecedent phenformin therapy was performed in fifteen cases and was associated with renal insufficiency in ten cases and liver disease in eight cases. Tissular anoxia of primary hemodynamic or respiratory origin was absent in all cases. The severe metabolic acidosis (pH m.93 +/- 0,03; HCO3-= 6 +/- 1 MM; PaCO2 = 18 +/- 2 MM. Hg) and hyperlactatemia (14.2 +/- 0.3 mM) were associated with high lactate/pyruvate ration (70 +/- 22). High alanine levels (up to 4.6 mM) were measured in some of these patients. High beta-hydroxybutrate levels were sometimes measured (up to 7.6 mM), and substantial amounts of acetoacetate were also detected in twelve cases. Glucagon level was always increased (1,050 +/- 240 pg./ml.), and insulin/glucagon ratio was low. Cortisol (49 +/- 10 mug./100 ml.) and HGH (10.8 +/- 0.6 ng./ml.) were also elevated. Increased plasma levels of phenformin were measured in five L.A. diabetic subjects (50 +/- 5 mug./ml.) by comparison with other phenformin-treated diabetic subjects. The specificity of the assay was investigated, and phenformin metabolites were characterized by thin-layer chromatography. Por the treatment of L.A., adjunction of dialysis and furosemide improved the efficacy of early and massive sodium bicarbonate infusion. It is suggested that accumulation of phenformin via renal insufficiency plays a determinant role in causing L.A. through an impairment of lactate metabolism in the liver. An accelerated epuration of the drug may be helpful in therapy of L.A. Phenformin treatment should be avoided in case of renal and/or liver insufficiency.
Diabetes 1975 Sep
PMID:Phenformin-induced lactic acidosis in diabetic patients. 80 37

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.
Diabetes 1977 Jan
PMID:Abnormalities of endogenous glucagon and insulin in unstable diabetes. 83 May 63

Glucagon response to insulin hypoglycemia was tested in diabetics with autonomic neuropathy (N=9), diabetics without neuropathy (N=8), and normals (N=9). With similar levels of hypoglycemia, growth hormone and plasma cortisol increased in all groups. The glucagon response in normals (121+/-19 vs. 308+/-30 pg./ml., mean+/-S.E.M. of baseline vs. hypoglycemia peak) was significantly less in nonneuropathic diabetics than in normals (128+/-13 vs. 209+/-30) and absent in neuropathic diabetes (128+/-23 vs. 115+/-20). Arginine stimulation produced a glucagon response in the neuropathic diabetics (106+/-16 vs. 523+/-103). The data indicate that the capacity to release glucagon during hypoglycemia is lost in diabetic neuropathy while glucagon responsiveness to arginine is retained. Neuropathy in diabetes may contribute to metabolic instability.
Diabetes 1977 Mar
PMID:Lack of glucagon response to hypoglycemia in diabetic autonomic neuropathy. 83 71

An extracorporeal "closed-loop" system has been employed to maintain glycemia in the normal range during consumption of meals in nine insulin-treated diabetics. This artificial pancreas system incorporated continuous blood glucose monitoring (0.05 ml. per minute, delay time 90 seconds), a computer programed to respond to glycemia, and a hormone delivery system. Intravenous insulin delivery rates were determined by control parameters responsive to both glucose concentration and its rate of change. Because insulin-dependent diabetics often defend themselves poorly against hypoglycemia (in some cases due to inadequate glucagon responses), the instrument was also programed for exogenous glucagon delivery. A priori selection of ideal parameters for insulin and glucagon delivery for each individual is not yet possible. Consequently, when the parameters were used for the first time on each subject, they were varied over a reasonable range. This approach resulted in a corresponding variety of glycemic responses, the average of which characterized a set of initial parameters that is generally applicable. Appropriate control parameters are presented that successfully prevented hypoglycemia. Glucagon delivery directly related to glycemia appeared sufficient for this purpose, thus obviating the need for dextrose administration. This system provides a technique for complete normalization of blood glucose concentration in the types of diabetics tested, during both fed and interprandial periods. It has yielded insights essential to the development of more sophisticated future devices.
Diabetes 1977 Jul
PMID:Normalization of glycemia in diabetics during meals with insulin and glucagon delivery by the artificial pancreas. 87 73

Glucagon suppression by somatostatin reduces or abolishes hyperglycemia in dogs made insulin-deficient by somatostatin, alloxan, or total pancreatectomy. This suggests that the development of severe diabetic hyperglycemia requires the presence of glucagon, whether secreted by pancreatic or newly identified gastrointestinal A cells, as well as a lack of insulin. Glucagon suppression could improve therapeutic glucoregulation in diabetes.
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PMID:Glucagon: role in the hyperglycemia of diabetes mellitus. 108 99

We recently demonstrated increased plasma glucagon but nomal insulin in rats fed a high-protein, carbohydrate-free (HP) diet; however, other investigators have reported that both plasma glucagon and insulin are increased after protein feeding. For this reason, we have investigated the ffects of an HP diet on pancreatic secretion of insulin and glucagon. Male rats were fed an HP or control diet for one, three, or five days, and, at the end of the feeding period, blood was taken for glucose, insulin, and glucagon determinations. Additional animals fed the HP and control diets for up to 10 days were sacrificed, the pancreases removed, and islets of Langerhans isolated. Islets were incubated for 30 minutes in media with glucose concentration of1.7, 8.3, 16.7, or 33.4 mM. Insulin and glucagon secreted into the media were determined by radioimmunoassay. Plasma insulin was markedly reduced after one day of HP feeding but gradually returned to normal by the fifth day. Plasma glucagon was not altered on day 1 but was significantly increased after three days of HP feeding. The I/G molar ratio, which declined precipitously on day 1, increased thereafter but, as shown previously, remained at a level that promotes gluconeogenesis for up to 10 days. Insulin secretion by isolated islets of control and HP rats increased more than 10-fold as medium glucose was raised from 1.7 to 16.7 mM. There was no difference in insulin release by the two groups of islets. Glucagon secretion by HP islest at low medium glucose remained normal during the first five days; however, beginning on day 3 there was gradual loss of the suppressive effect of high medium glucose on glucagon secretion. After one week of HP feeding, glucagon secretion at low medium glucose was doubled and there was complete lack of suppression of the elevated hormone production by high medium glucose. The alterations of alpha-cell function induced by HP feeding are similar to those found in human and experimental diabetes.
Diabetes 1976 Jan
PMID:A nonsuppressible increase of glucagon secretion by isolated islets of high-protein-fed rats. 110 94

Although the stimulatory effect of glucagon on gluconeogenesis has been well demonstrated in certain systems in vitro, this effect has never been established in man. The present study was undertaken, therefore, to determine whether glucagon could stimulate gluconeogenesis from alanine in normal fasting man. Glucagon might stimulate this process by increasing the hepatic alanine uptake and/or by shunting the extracted alanine within the liver into the gluconeogenic pathway. In order to be able to examine these two aspects of gluconeogenesis, we combined the hepatic vein-brachial artery catheterization technic with an istopic infusion of alanine-14C. Alanine-14C specific activity was measured in whole blood and plasma by use of a rapid chromatographic technic. Since plasma contributed 93 per cent of the alanine extracted by the splanchnic bed with a specific activity three times that of the red blood cells, plasma alanine specific activity was used to study the conversion of alanine to glucose. A constant infusion of alanine-14C achieved a relatively stable arterial specific activity by forty minutes. The administration of glucagon by constant infusion (15-50 ng./kg./min.) had no affect on thf splanchnic extraction of alanine. Net splanchnic glucose-14C production, however, doubled during the glucagon infusion, and the conversion of alanine to glucose increased from 30 plus or minus 2 to 58 plus or minus 9 mumol/min. These data (1) demonstrate that in normal man fasted twelve to fourteen hours, glucagon at supraphysiologic levels can double the rate of gluconeogenesis from alanine and (2) indicate that this stimulatory effect of glucagon is exerted within the liver by shunting the extracted alanine toward new glucose formation rather than by increasing the hepatic extraction of alanine.
Diabetes 1975 Jun
PMID:Gluconeogenesis from alanine in normal postabsorptive man. Intrahepatic stimulatory effect of glucagon. 114 May 13

Eight normal subjects and ten diabetic patients were studied to compare the response of plasma insulin to glucagon with that to glucose and tolbutamide. Oral glucose tolerance test, glucagon test and tolbutamide-glucagon test were performed at intervals of several days. In glucose tolerance test, insulin response was reduced in the patients with severe diabetes. Plasma insulin increased and reached the peak 3 min after glucagon injection (glucagon I) in the normal controls, while plasma insulin response was reduced in diabetic patients, especially in the severe diabetics. In the normal controls plasma insulin rose and reached the peak 6 min after the tolbutamide injection and thereafter fell to the initial level. Glucagon injection following tolbutamide (glucagon II) caused the rise in insulin in the control subjects. In diabetics insulin response to either tolbutamide or glucagon I was reduced. Tolbutamide or glucagon II caused a significant difference in plasma insulin response in all the diabetic groups compared with the normal subjects, while glucose or glucagon I showed a significant increment of plasma insulin between the normal subjects and the severe diabetics. These results suggest that injection of tolbutamide as well as glucagon II provides a definite discrimination of insulin response in diabetics from the normal controls. The usefulness of the tolbutamide-glucagon test in the diagnosis of diabetes mellitus was discussed. -- glucose tolerance test; glucagon test; tolbutamide-glucagon test; plasma insulin.
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PMID:Glucagon-induced insulin secretion in normal diabetic subjects. 115 79


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