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.
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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.
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PMID:Carbohydrate metabolism and pancreatic islet-cell function in thalassemia major. 32 76

Carbohydrate metabolism was studied in fourteen patients with myotonia dystrophica (MD) using oral glucose, fructose and galactose tolerance tests. Insulin responses to tolbutamide, glucagon, arginine and leucine were determined and insulin resistance was measured with exogenous iv insulin. Glucose tolerance was impaired in twelve of the four teen subjects while hyperinsulinism was found in all patients studied. Insulin response to the various substances was excessive. The insulin tolerance test revealed insulin resistance in all patients and this generally correlated well with the degree of hyperinsulinism to provocative tests. Serum galactose levels after an oral load were much lower in MD compared to normal subjects and were associated with a correspondingly greater rise in glucose, indicating an increased conversion of galactose to glucose. A similar response to oral galactose was found in diabetics. The hyperinsulinism seen with the fructose and galactose tests corresponded well to the rise in glucose during the test. Urinary sorbitol excretion was normal. It is concluded that the impaired carbohydrate metabolism seen in MD is due to peripheral insulin resistance affecting various organs including the liver and it is suggested that the excessive beta-cell response is secondayr to the peripheral resistance.
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PMID:Carbohydrate metabolism and insulin resistance in myotonia dystrophica. 32 Feb 24

Various types of insulin secretion may be differentiated in diabetes mellitus. In juvenile diabetes, there can not be induced in general any stimulation of insulin secretion, whereas in maturity-onset type diabetes a significant increase of the serum level was found after stimulation with glucagon or tolbutamide. However, neither moderate glucose doses given orally nor very high glucose doses given intravenously were able to stimulate insulin secretion in some of these patients. These findings suggest a complete insufficiency of beta cell glucose receptors in this specific type of maturity-onset diabetes.
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PMID:[Various disturbances in beta cell function in diabetes mellitus]. 33 25

A case of islet cell hyperplasia in a ten year old black male with symptomatic fasting hypoglycemia was documented histopathologically. Provocative studies with glucose, tolbutamide, glucagon, and diazoxide were performed to test the insulin response of hyperplastic islets. The islets responded to glucose, glucagon, and tolbutamide. Diazoxide potentiated the tolbutamide-induced insulin response, and this effect of diazoxide was not blocked by propranolol. In the diagnostic work up of islet cell hyperplasia, dizoxide may paradoxically potentiate tolbutamide-induced insulin release, a finding which may falsely suggest progression of the disease.
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PMID:Paradoxical enhancement of tolbutamide-induced insulin release by diazoxide in a patient with islet cell hyperplasia. 35 39

In order to investigate whether patients with long-standing juvenile diabetes mellitus (onset of diabetes before the age of 30) and a low daily insulin requirement (less than 0.50 units/kg body weight) still have functioning B-cells, plasma C-peptide was determined after stimulation (OGTT and glucagon/tolbutamide) in 64 patients with diabetes of more than 18 years' duration (mean 31 years). Measurable endogenous insulin production was found in 24% of the patients. The prevalence of severe retinopathy was lower in the secretors than in the non-secretor group. There was no difference in insulin antibody concentration between the two groups. Furthermore, the insulin requirement in the secretor group was relatively constant during the course of diabetes. Metabolic control was similar in both groups. It is concluded that a persisting but low activity of endogenous insulin production can be found in many long-term juvenile diabetics with a low insulin requirement, while others without any residual beta-cell function develop a low insulin requirement for unknown reasons.
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PMID:Persistent insulin secretion, assessed by plasma C-peptide estimation in long-term juvenile diabetics with a low insulin requirement. 35 94

Insulin and glucagon have been studied in 20 subjects (both of the subjects' parents were diabetic or in case of only one diabetic parent, the other showed a first degree familiarity of diabetes): 10 showed normal glucose tolerance ('true prediabetics') and 10 impaired glucose tolerance ('genetic chemical diabetes'). Mean insulin response to oral (100 g) and i.v. glucose load (200 mg/kg followed by 20 mg/kg/min for 60 min) and to arginine infusion (25 g in 30 min) was normal in the prediabetics and delayed and higher in the subjects with chemical diabetes as compared to the control group. Glucagon response to arginine was higher, but not significantly, in prediabetics and in subjects with chemical diabetes. In both of these groups glucagon suppression by glucose was not observed. The insulin/glucagon molar ratio was significantly reduced after glucose infusion in these two groups. No correlation was found between insulin and glucagon secretion after arginine or glucose. A possible alteration in the mechanism controlling glucagon secretion even in the earliest phases of diabetes is suggested.
Acta Diabetol Lat
PMID:Glucagon and insulin secretion in potential diabetes. 36 Jul 48

To determine the dynamics of insulin and of glucagon secretion in response to several sequential stimuli administered shortly after an arginine pulse (5 g), 20 nonobese, apparently healthy volunteers were given arginine (5 g), glucose (5 g), and tolbutamide (1 g) by rapid intravenous injection. The early insulin and glucagon area 0-8 min was studied. At the intervals and with the dosages used in this study, different stimuli with and without prestimulation with arginine did not lead to changes in early secretion of insulin. There was no exhaustion of the pool of insulin released after multiple sequential pulses. These results suggest a pattern in which stimulation induces a rapid release of insulin and activates the interchange between the stored and labile insulin pool; the 8-min interval is sufficient for the rapid return of the two compartments to a state of equilibrium. Also for glucagon, subsequent different stimuli did not exhaust glucagon release; nevertheless, glucagon is immediately suppressed by a submaximal glucose pulse.
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PMID:Early insulin and glucagon response to subsequent pulses of arginine, glucose, and tolbutamide in normal man. 36 91

Normal and hypophysectomized (hypox) rats, fed ad libitum, received intraperitoneal injections of tolbutamide (75 mg/kg/day) or of saline for 6 weeks. 24 h after the last injection, blood samples were taken for glucose, insulin and glucagon determinations. In normal rats, tolbutamide treatment did not alter serum glucose, insulin and glucagon, although it suppressed the secretion of insulin and glucagon by the pancreatic islets. In hypox rats, tolbutamide decreased serum glucose and insulin, elevated serum glucagon and stimulated the secretion of glucagon, but not that of insulin by the pancreatic islets. In addition, tolbutamide treatment increased the glucagon response to arginine in normal, but not in hypox rats. The serum glucose response to arginine was decreased by tolbutamide treatment and by hypophysectomy and, thus, appeared independent of the glucagon rise or preexisting glucagon level. We conclude that tolbutamide treatment decreased the secretion of glucagon and insulin in normal rats and stimulated that of glucagon in hypox rats, perhaps because of the low levels of insulin in the serum and in the pancreas of the latter. Our results are compatible with the hypothesis that the pancreatic action of tolbutamide is influenced by the pituitary.
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PMID:Secretion of glucagon and insulin in hypophysectomized rats: effect of tolbutamide. 38 97

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


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