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)

A new, spontaneously diabetic syndrome has been recognized in nonobese outbred Wistar rats of both sexes. The age at detection of first glycosuria has varied from 48 to 120 days, with a mean of 67 days. Eighteen rats have been studied, 14 untreated and four during and after cessation of insulin treatment. The affected animals have demonstrated a spectrum of severity, with hyperglycemia (252-732 mg./dl.), hypoinsulinemia (0-1 ng./ml.), and hyperketonemia. The severely ketotic rats, with total blood ketone body levels between 6 and 13 mM, showed rapid loss in weight and dehydration over one to six days. The moderately ketotic (1-5 mM) declined gradually in weight over 15 days, with marked polyuria and glycosuria. The stable rats, with ketonemia less than 1 mM, sustained their weights, polyuria, and glycosuria for longer than 40 days. A relative or absolute increase in plasma immunoreactive glucagon and elevated levels of free fatty acids and branched-chain amino acids were observed in relation to the severity of the syndrome. Intraperitoneal arginine or tolbutamide elicited no insulin response, but the glucagon response to arginine was exaggerated. Pancreatic insulin content was normal or moderately decreased. Light-microscopic examination of pancreases of ketotic animals at the end stage of the disease showed islets to be very small and rare, consisting virtually of non-beta cells. In stable and earlier ketotic rats, the islets were small, with reduction in beta-cell number and a striking inflammatory cell infiltration. Surviving beta cells showed variable degranulation. This model of spontaneous diabetes in nonobese rats displays insulin deficiency, glucagon excess, and ketosis, with a dramatic inflammatory lesion during active beta-cell destruction.
Diabetes 1977 Feb
PMID:The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. 32 72

To investigate the development of diabetes mellitus in patients with thalassemia major, plasma glucose and immunoreactive insulin (IRI) levels following oral glucose and intravenous tolbutamide and glucose disappearance rates following intravenous insulin were measured in 10 patients before and during five years on a high transfusion program (HTP). Plasma immunoreactive glucagon (IRG) levels following oral glucose, intravenous insulin, and arginine were measured during the sixth year. Serial percutaneous liver biopsies were performed on seven patients. The oral glucose tolerance tests (OGAT) and mean peak IRI levels were normal in nine of 10 patients before HTP. After HTP was begun a progressive deterioration of OGTT occurred despite normal IRI levels. Following tolbutamide, the mean per cent fall in plasma glucose in the patients before HTP was significantly less than in controls (p less than 0.01) and similar to that of controls during five years of HTP in spite of higher than normal peak IRI levels. Of seven survivors after six years of HTP, three had normal OGTT and four had chemical diabetes; mean peak IRI levels were normal, but fasting IRG levels were significantly higher than in controls (p less than 0.05). In all seven patients, plasma IRG failed to increase following insulin-induced hypoglycemia and was significantly higher than in controls after arginine (p less than 0.01); after oral glucose, plasma IRG fell significantly below that of fasting only in the patients with chemical diabetes (p less than 0.03). Following intravenous insulin, the mean per cent fall in glucose before and during HTP was significantly less than in controls (p less than 0.01). Hemosiderosis and cirrhosis were present in all biopsied patients. Four patients died; two had chemical and two had nonketotic insulin-dependent diabetes. These data suggest that diabetes mellitus occurs frequently in patients with thalassemia on HTP and that insulin resistance and hyperglucagonemia, possibly due to cirrhosis, are important etiologic factors.
Diabetes 1977 Mar
PMID:Carbohydrate metabolism and pancreatic islet-cell function in thalassemia major. 32 76

The A-, D-, and B-cells--the islet cells that contain, respectively, immunoreactive glucagon, somatostatin, and insulin--are distributed within a specialized heterocellular region of the islets of Langerhans as if to permit heterologous contacts between all three cell types. Inasmuch as each one of the three secretory products of these three cell types influences the secretion of at least one of its neighboring cells, "paracrine" influence on islet hormone secretion becomes a reasonable hypothesis. Glucagon stimulates both insulin and somatostatin release, while insulin and somatostatin both inhibit glucagon release, providing the basis for a feedback relationship through which A-cell secretion may be restrained. In addition, glucagon-mediated insulin secretion may be estrained by glucagon-stimulated somatostatin release. Such intercellular relationships could help determine the composition of the insulin and glucagon mistures released within a given metabolic setting.
Diabetes 1977 Mar
PMID:Possible roles of the pancreatic D-cell in the normal and diabetic states. 32 77

Effect of synthetic gastric inhibitory polypeptide (GIP) on insulin and glucagon secretion was stuied in vivo and in vitro in the rat. Intravenous administration of 1 microng./kg. GIP along with 0.625 gm./kg. glucose caused a more prominent rise of plasma insulin than did 0.625 gm./kg. glucose alone. The suppression of plasma glucagon levels induced by glucose was attenuated partially but not significantly by the concomitant administration of GIP. GIP (1 microng./kg. i.v.) alone raised both plasma insulin and glucago levels. In in-vitro experiments with isolated pancreatic islets, GIP significantly augmented insulin release induced by either 8.3 mM or 16.7 mM glucose, whereas the augmentation of glucagon release was observed at 3.3 mM, 8.3 MM, and 16.7 mM glucose concentrations. Three peptides, consisting of 1-28, 22-43, and 15-43 amino acids of GIP, failed to potentiate insulin and glucagon secretion. These results suggest that synthetic GIP has a stimulating effect on insulin and glucagon secretion.
Diabetes 1977 May
PMID:Synthetic gastric inhibitory polypeptide. Stimulatory effect on insulin and glucagon secretion in the rat. 32 91

Somatostatin, a peptide inhibitor of growth hormone release originally isolated from the hypothalamus, is also present in D cells of pancreatic islets. Its ability to inhibit the secretion of insulin and glucagon suggests that it may be a local regulator of pancreatic A- and B-cell function. Studies using synthetic somatostatin have provided evidence that glucagon is a physiologically important hormone that exacerbates the consequences of insulin deficiency in human diabetes mellitus. The ability of somatostatin to diminish both fasting and post-prandial hyperglycemia and to forestall the development of ketoacidosis after withdrawal of insulin in insulin-dependent diabetics suggests a potential therapeutic use of this agent in diabetes. Presently, however, its short half-life and diverse actions preclude such use and have prompted the search for more specific and longer-acting analogs.
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PMID:Somatostatin. Its possible role in carbohydrate homeostasis and the treatment of diabetes mellitus. 32 23

Gastric inhibitory polypeptide (GIP) is insulinotropic and is released after ingestion of glucose in normal man. Changes in plasma immunoreactive gastric inhibitory polypeptide (IRGIP) were therefore studied during a 50-gm. oral glucose tolerance test in 10 normal subjects and 20 subjects with maturity-onset diabetes mellitus. The diabetics were nonobese and treated by diet alone; they exhibited exaggerated increments of plasma IRGIP in association with delayed and diminished peak increases in plasma immunoreactive insulin, suggesting relative failure of the beta-cell response to GIP. The diabetic subjects also showed a paradoxic rise in mean plasma immunoreactive glucagon, with a peak coinciding with that of plasma IRGIP. It is suggested that the defective beta-cell response may lead to diminished feedback inhibition of GIP secretion by insulin in diabetes mellitus and that the glucagonotropic action of GIP may be expressed under these conditions.
Diabetes 1977 Jun
PMID:Hypersecretion of gastric inhibitory polypeptide following oral glucose in diabetes mellitus. 32 34

Pancreatic beta-cell secretory activity was measured in 17 patients with insulin-dependent diabetes mellitus of less than 19 months' duration and in 10 nondiabetic subjects by means of the peripheral plasma C-peptide response to 1 mg. of glucagon I.V. The C-peptide response to a meal was also measured in the diabetic patients. Residual beta-cell function was present in all the diabetic patients as indicated by significant amounts of C-peptide in plasma. Significant increases in C-peptide were observed in 16 after glucagon stimulation and in 15 after the meal. Both absolute and relative increase in C-peptide were reduced in the diabetic patients. The increase in C-peptide was correlated to the fasting C-peptide concentration both after glucagon (r=0.86, p less than 0.001) and after the meal (r=0.66, p less than 0.01). The responses to the meal and to glucagon were correlated (r=0.77, p less than 0.005), indicating a high predictive value of the glucagon test as to how the beta-cells will respond during normal daily life.
Diabetes 1977 Jul
PMID:C-peptide response to glucagon. A test for the residual beta-cell function in diabetes mellitus. 32 4

In order to correlate the different cell types of the human endocrine pancreas to a specific secretion product, an immunoelectron microscopic localization of the hormones whose production had been attributed to pancreatic islets was conducted. Glucagon and insulin were respectively localized in the typical A- and B-cells, whereas no subclasses of A-cells could be identified. With antibodies that reacted with the gastrin cells in the human gastric mucosa, it was not possible to detect gastrin in any of the islet cell types. In confirmation of recent results obtained by light microscopy, somatostatin was found in all the typical D-cells containing large, weakly electron-dense secretory granules. The human pancreatic polypeptide (HPP), a newly postulated hormone, was clearly associated with a fourth cell type, which is characterized by the presence of small secretory granules (100-150 nm.). These results suggest that each of the four cell types that are easily identifiable by ultrastructural observations is responsible for the production of a specific secretory product.
Diabetes 1977 Aug
PMID:Identification of four cell types in the human endocrine pancreas by immunoelectron microscopy. 32 32

Alloxan infused into the isolated perfused rat pancreas caused transient insulin secretion release. Alloxan poisoning also prevented subsequent induction of glucose-mediated unsulin release and also prevented the inhibition of glucagon release by glucose. Glucose or 3-O-methylglucose infused simultaneously with alloxan protected the alpha- and beta-cell, allowing subsequent glucose inhibition of glucagon secretion and stimulation of insulin release. The above alloxan effects were dose-related, the alpha-cell being one fourth as sensitive to alloxan as the beta-cell. The data indicate that (1) alloxan and glucose suppression of amino-acid-stimulated glucagon secretion is independent of concomitant insulin secretion; (2) alloxan, like glucose, affects alpha-and beta-cells directly, stimulating the beta-cell and inhibiting the alpha-cell; and (3) alloxan acts on a glucoreceptor system with comparable physicochemical characteristics common to both cell types.
Diabetes 1977 Oct
PMID:Glucose and 3-O-methylglucose protection against alloxan poisoning of pancreatic alpha and beta cells. 33 68

Thirty-nine patients (14 non-diabetics, 8 chemical diabetics, and 17 overt diabetics) with circulating islet cell antibodies (ICA) were studied. Insulin and glucagon secretion after oral (100 g) and intravenous glucose loading (200 mg/kg bolus injection followed by an infusion of 20 mg/min over 60 min) and arginine infusion (25 g over 30 minutes) were evaluated in these patients and in non diabetic and diabetic ICA-negative controls. In the non-diabetic groups with or without ICA, insulin and glucagon responses to glucose were similar. Moreover, in ICA positive patients the response of these hormones to arginine infusion was reduced. Similar alterations in insulin and glucagon secretion were observed in the CIA positive and negative patients with chemical or overt diabetes. In particular, fasting hyperglucagonaemia and glucagon hyperresponse to arginine are associated with a lack of insulin secretion in the patients with overt diabetes. Hormonal differences between diabetics with and without ICA could not be detected.
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PMID:Insulin and glucagon secretion in diabetic and non-diabetic patients with circulating islet cell antibodies. 33 69


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