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)

Diazoxide 5 mg/kg/day was administered to four normal subjects for five days and, together with insulin, to ten diabetic subjects for seven days. In every case there was a substantial increase in the insulin response to combined stimulation of the pancreatic beta cells with 1 mg of glucagon and 2 g of tolbutamide given intravenously. Similar increases were not seen in four diabetics who received placebo with insulin. It is likely that the observed improvements reflected increased insulin stores which resulted from diazoxide inhibition of insulin release. These findings suggest that poor insulin responses in diabetics may be due, at least in part, to chronic overstimulation of the beta cells. Pharmacological agents such as diazoxide, which inhibit glucose-induced insulin release, may have a place in preserving and restoring insulin secretion in diabetes.
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PMID:Improvement in insulin secretion in diabetes after diazoxide. 5 17

There are several situations in which medical therapy of hyperinsulinism induced by islet cell tumors or hyperplasia is necessary and at present we have at our disposal several drugs which are capable of reducing endogenous hyperinsulinism. They are: -Streptozotocin, which represents today the most useful therapeutic agent for beta cell carcinoma therapy; -Diazoxide, which represents the drug of first choice for the treatment of most hypoglycemic syndromes caused by islet cell adenoma or hyperplasia; -Propranolol, Chlorpromazine, Diphenylhydantoin, which may be regarded as a useful alternative to diazoxide, although they are capable of giving rather inconstant results. These drugs may today effectively substitute for corticosteroids and glucagon in the medical treatment of almost every chronic hyperinsulinemic hypoglycemic syndrome, including malignant beta cell carcinoma.
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PMID:Medical treatment of endogenous organic hyperinsulinism. 17 29

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

The influence of previous exposure to glucose on the subsequent B- and A(2)-cell secretory responses to arginine was investigated in the perfused pancreas of the rat. Arginine (8 mM) was administered in two brief (9 min) pulses separated by a period of 66 min. In pancreata from 18-h-fasted animals the two pulses of arginine elicited biphasic glucagon secretory responses, while stimulation of insulin release was barely detectable. When 27.7 mM glucose was administered for 30 min during the intervening period up to 20 min before the second pulse of arginine, the glucagon response to arginine was diminished by 55% while the insulin release was markedly increased in comparison with the first pulse. 8.3 mM glucose, when administered before the second pulse of arginine, exerted effects that were smaller but otherwise similar to those of 27.7 mM glucose.The inclusion of 3.9 mM glucose during the stimulation periods with arginine decreased the glucagon and greatly increased the insulin secretory response. Under these conditions, previous exposure to 27.7 mM glucose inhibited the glucagon and enhanced the insulin response to the second stimulatory pulse of arginine to the same relative degree as when arginine was administered alone. Diazoxide (2 mM), when administered together with 27.7 mM glucose, almost completely inhibited insulin release induced by the presence of glucose, yet did not influence the modulation exerted by glucose on the subsequent insulin and glucagon secretory response to arginine. Conversely, these effects of the glucose pulse could not be reproduced by 1 mug/ml of porcine insulin. Previous exposure to glyceraldehyde (10 mM) mimicked the glucose effects.Also, in pancreata from fed rats, previous exposure to 27.7 mM glucose markedly inhibited subsequent arginine-induced glucagon secretion while the concomittant insulin response was enhanced.IT IS CONCLUDED THAT: (a) both A(2)- and B-cell responsiveness is modulated by a previous exposure to glucose which produces opposite effects in the two cell types, (b) this action of glucose does not depend on its insulin-releasing capacity, and (c) instead, a "memory" of glucose is induced as a consequence of the metabolism of the sugar in the A(2) and B cells.
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PMID:Glucose memory of pancreatic B and A2 cells: evidence for common time-dependent actions of glucose on insulin and glucagon secretion in the perfused rat pancreas. 38 26

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 secretion of insulin and glucagon was investigated in pancreatic islets from diabetic and nondiabetic sand rats of similar age and weight. The metabolic characterization was based on an intraperitoneal glucose tolerance test. Compared to nondiabetic animals diabetic sand rats had a diminished insulin content in their islets and a decreased insulin secretory response to glucose, glyceraldehyde and theophylline. Diazoxide inhibited insulin release in diabetic as well as in nondiabetic sand rats whereas mannoheptulose was effective only in the nondiabetic rats. There was no significant difference in glucagon content between the two groups. The glucagon secretion by pancreatic islets of diabetic animals was not suppressed by glucose, as in nondiabetic sand rats islets, but by glyceraldehyde. This indicates that the sensitivity to glucose rather than the suppressibility of glucagon release was altered.
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PMID:Insulin and glucagon secretion by pancreatic islets from nondiabetic and diabetic sand rats (Psammomys obesus). 76 20

Infusion of diazoxide (16.5 mg./kg. in 10 minutes) into normal unanesthetized dogs resulted in a prompt hyperglycemia due to increased hepatic glucose production as measured with a 3-3H-glucose primer-infusion technique. Plasma insulin and glucagon were decreased. Glucose uptake failed to increase. Diazoxide administration during period of alpha adrenergic receptor blockade with phentolamine still caused hyperglycemia and increased glucose production. Glucose uptake was inhibited despite adequate plasma insulin. Infusion of somatostatin along with insulin prevented the effects of diazoxide on plasma glucose and glucose production. It is concluded that diazoxide hyperglycemia is not due solely to decreased insulin secretion or increased epinephrine secretion and that glucagon is not a contributory factor. Diazoxide may act directly to increase glucose production and inhibit glucose uptake. Somatostatin appears capable of blocking the effect of diazoxide on glucose production by an unknown mechanism.
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PMID:On the mechanism of diazoxide-induced hyperglycemia. 90 62

Five infants with persistent hypoglycaemia due to hyperinsulinism were reported. Provocative tests for insulin release were unhelpful. Diazoxide was useful in the treatment of three patients but many side-effects were observed. These included petechial rash, hypertrichosis, acute renal failure, fluid retention and cardiac failure. Two patients underwent spontaneous remission. Three patients had nesidioblastosis, two of whom were subjected to 95% pancreatectomy. Postoperatively, recurrence of hypoglycaemia was due to hyperinsulinism in one patient and to presumed glucagon deficiency in the other. Phenytoin effectively corrected the hypoglycaemia in the patient who had postoperative hyperinsulinism. It is recommended that medical therapy with diazoxide (10-15 mg/kg per day) together with a diuretic be commenced once hyperinsulinism is diagnosed. Subtotal pancreatectomy should be performed early in these patients if hypoglycaemia cannot be controlled with medical therapy or if side-effects of treatment are documented.
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PMID:Hyperinsulinism in infancy. 276 41

The relation between hepatic glucose production rate (HGPR) and plasma concentrations of insulin and glucagon was investigated in four term neonates who had severe hypoglycaemia. The hepatic glucose production rate was less than 20% of normal for fasting term neonates in all four babies and yet insulin concentrations were never greater than 12 microU/ml; two babies had very low glucagon concentrations (less than 60 ng/l). Two further neonates with similar histories also had plasma glucagon concentrations that were also extremely low (less than 20 ng/l). A single intravenous bolus of glucagon caused a rapid rise in hepatic glucose production rate towards the normal range, which was sustained for many hours after the bolus had been given. Diazoxide given to one baby suppressed previously 'normal' insulin concentrations still further (4.2 to less than 1.6 microU/ml) and thereby restored the hepatic glucose production rate to normal. In view of the normal plasma insulin concentrations at a time when the hepatic glucose production rate was reduced, we feel that the absolute concentration of insulin may be less important than the insulin/glucagon molar ratio in the control of glucose homeostasis in this group of infants. The changing of this ratio by means of boluses of glucagon may be useful in preventing rebound hypoglycaemia, which so often occurs when dextrose infusions are reduced either accidentally or in an attempt to restart oral feeds.
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PMID:Effect of diazoxide or glucagon on hepatic glucose production rate during extreme neonatal hypoglycaemia. 331 27

Diazoxide was used to prevent the high insulin secretion after glucagon administration to rabbits. Using of this benzothiadiazine allowed to investigate an effect of glucagon on the blood glucose, free fatty acids and triglycerides without raised insulin. The concentration of serum glucose was increased in all experiments (with or without diazoxide infusion), however both normoinsulinemic and hyperinsulinemic rabbits showed return to the control value in the end of experiments. In the case of FFA the high level of insulin was necessary to return their concentration to the control value. Glucagon alone had no effect on serum TG level.
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PMID:[Use of diazoxide in the studies of the effect of glucagon on the blood serum levels of glucose, free fatty acids and triglycerides in rabbits]. 333 61


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