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)

In the 13 years since hepatic glycogen synthetase deficiency was first described in identical twins no further cases seem to have been observed. We report a child who had suffered from occasional morning convulsions since the age of 7. Three 24-hour metabolic profiles showed fasting hypoglycaemia, hyperketonaemia, but normal lactate. Hyperglycaemia and hyperlactataemia occurred after meals. Glucagon caused a rise in glucose 3 hours after a meal with a fall in lactate and alanine; no effect of glucagon was seen after a 12-hour fast. Normal increments in glucose followed oral galactose or alanine. Liver and abdominal wall muscle biopsies were taken. Glycogen content was subnormal in liver but normal in muscle. Glycogen synthetase (EC 2.4.1.11) was virtually absent from liver but fully active in muscle. Hepatic glycogen synthetase deficiency causing fasting hypoglycaemia has been confirmed. It is postulated that some children with "ketotic hypoglycaemia" may suffer from this disorder.
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PMID:Hepatic glycogen synthetase deficiency. Definition of syndrome from metabolic and enzyme studies on a 9-year-old girl. 14 12

In idiopathic or generalized epilepsy, serum glucose and cholesterol concentrations tend to be low, especially just before the seizure. Glucose tolerance curves are abnormal and variable. The electrolyte balance is disturbed, and epileptics tend to go readily into alkalosis. Serum [Na+] is usually unaffected, but [K+] is normal to low between attacks and increases during and after the seizure. Serum [Cl-] is usually high just before the seizure. Epileptics are generally mildly hypocalcemic, especially in the period before the seizure. Serum urea and nonprotein nitrogen values are low between paroxysms but increase after the seizure. Serum protein concentration is usually normal. Stress, which releases epinephrine and corticotropin, results in high serum citrate concentration, which probably contributes to decreased serum [Ca2+] just before a seizure. In the healthy individual, any increase in serum citrate is accompanied by increasing [Ca2+]. In the rabbit, convulsions can be induced with corticotropin, a result of increased serum citrate concentration coupled with a decrease in [Ca2+]. The net result is severe hypo-ionic-calcemia. A similar phenomenon has been reported in a few humans. Administration of insulin causes serum citrate concentrations to decrease. Apparently, the dynamic system that controls glucose and lipid metabolism, and thus electrolyte balance, through the hormones epinephrine, corticotropin, insulin, glucagon, calcitonin, and parathormone, is abnormal in the epileptic.
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PMID:Clinical biochemistry of epilepsy. I. Nature of the disease and a review of the chemical findings in epilepsy. 22 Nov 36

Persistent hypoglycemia in the neonate and young infant usually results from inappropriate, excessive secretion of insulin, or a deficiency of one of the hepatic gluco-regulatory enzymes. Hypoglycemia due to hyperinsulinism, whether associated with nesidioblastosis, islet cell hyperplasia, adenoma or normal islets, may have devastating consequences in this age group and demands recognition and effective treatment. Medical management consisting primarily of frequent feeding, the intravenous infusion of glucose and the administration of glucagon, glucocorticoids, epinephrine, and diazoxide is often ineffective and may be punctuated by repeated episodes of hypoglycemia, convulsions, and central nervous system damage. Although subtotal-total pancreatectomy is effective in restoring blood sugar to normal, almost half of the reported patients are mentally retarded. This may be due in part to unwarranted delays in performing pancreatectomy. Experience with 6 patients undergoing subtotal--total pancreatectomy for intractable hypoglycemia supports the contention that this procedure is effective. A euglycemic state was restored in all 6 patients and there was no evidence of residual central nervous system damage. The spleen should be preserved in view of its importance in maintaining normal immunodefense mechanisms.
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PMID:Neonatal and infantile hypoglycemia due to insulin excess: new aspects of diagnosis and surgical management. 32 12

The role of glucagon in regulating plasma lipid concentrations (nonesterified fatty acids, ketone bodies, and triglycerides) is reviewed. The effects of glucagon-induced insulin secretion upon this lipid regulation are discussed that may resolve conflicting reports in the literature are resolved. In addition, the unresolved problem concerning the pharmacologic versus physiologic effects of glucagon is stressed. Glucagon's role in stimulating lipolysis at the adipocyte serves two important functions. First, it provides plasma nonesterified fatty acids for energy metabolism and secondly, it ensures substrate for hepatic ketogenesis. In vitro, glucagon's lipolytic activity has been consistently observed, but in vivo, this activity has sometimes been obscured by the effects of glucagon-induced insulin secretion. Frequently, a biphasic response has been reported in which a direct lipolytic response is followed by a glucagon-induced insulin suppression of plasma nonesterified fatty acid concentration. When the glucagon-induced insulin secretion has been controlled by various in vivo techniques, glucagon's lipolytic activity in vivo has frequently been demonstrable. In the 1960s, in vitro liver perfusion experiments demonstrated that glucagon enhanced hepatic ketogenesis independent of glucagon's lipolytic activity. However, this direct effect of glucagon on the hepatocyte was not universally accepted because of conflicting reports in the literature. Failure to observe an in vitro ketogenic effect of the hormone in some studies may have been due to suboptimal experimental conditions. Certain factors are now known to influence the ketogenic response, such as the concentration of fatty acids in the media and the nutritional status of the animal. Under optimal in vitro conditions with liver preparations from fed animals, the ketogenic response to physiologic concentrations of glucagon has been demonstrated. However, further study is necessary to define the quantitative ketogenic role of the hormone. In spite of this early in vitro work, glucagon was not definitely shown to be ketogenic in vivo (independent of fatty acid availability) both in the rat and in diabetic man until 1975. Since these observations, several reports have confirmed the ketogenic action of glucagon in vivo by direct hepatic catheterization experiments. Glucagon's role in decreasing hepatic triglyceride synthesis and secretion in vitro has been repeatedly shown but the mechanism is unresolved. This lipid regulatory action of glucagon has been more difficult to demonstrate in vivo because of the many variables that affect triglyceride synthesis. Under specific experimental conditions, however, glucagon has been shown to decrease plasma triglyceride concentration in man at both physiologic and pharmacologic concentrations. Hepatic catheterization experiments have also confirmed this effect in man. The regulation of lipids by glucagon fits well into its role as a stress hormone...
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PMID:The role of glucagon in the regulation of plasma lipids. 37 41

In a newborn baby, suffering from persistent severe hypoglycaemia with convulsions glucagon deficiency was shown. Treatment with zinc-protamine-glucagon injection twice daily resulted in normal blood glucose levels. Motor development is delayed.
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PMID:Persistent neonatal hypoglycaemia due to glucagon deficiency. 66 60

A new-born baby with Beckwith's syndrome had severe hypoglycaemia, and was treated with glucagon and prednisone. Treatment was stopped at 1 month of age and his blood glucose levels were satisfactory for the ensuing 6 weeks. However, at 10 weeks of age, he had a hypoglycaemic convulsion and required large doses of diazoxide and prednisone for the next 2 months to maintain the blood glucose above 40 mg/100 ml. Insulin excretion was raised until he was 4 months old. Cases of Beckwith's syndrome which develop hypoglycaemia, should be treated with diazoxide and corticosteroids until insulin excretion is normal.
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PMID:Management of prolonged hypoglycaemia in Beckwith's syndrome. 87 Aug 93

Plasma glucose, insulin and glucagon concentrations were measured before and after the ingestion of a protein-rich meal in 11 healthy pregnant women in the last trimester of pregnancy, and again in the same subjects postpartum. Compared to postpartum, basal levels of plasma glucose were lower in late pregnancy whereas basal insulin and glucagon concentrations were both enhanced. After the meal, insulin and glucagon concentrations in plasma increased in gestation as well as postpartum. Plasma glucose increased slightly in pregnancy but remained unchanged postpartum. The mean insulin response to the meal was unaffected by pregnancy whereas that of glucagon was reduced. Thus following protein ingestion, plasma glucose rose in pregnancy in spite of unchanged levels of insulin and depressed levels of glucagon. Favouring analbolism, the reduced glucagon response to protein ingestion in pregnancy fits in the concept of 'facilitated anabolism' in late pregnancy and, moreover, it lend further support to the idea that changes in glucagon secretion per se are not involved in the pathogenesis of the diabetogenicity of pregnancy.
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PMID:Effect of pregnancy on the glucagon response to protein ingestion. 88 72

A new active peptide was purified from the acid-alcohol extract of pork pancreas. It markedly suppressed the insulin activity detected by either in vivo mouse convulsion assay or in vitro free-fat cell assay. When the extract was subjected to chromatography on a carboxymethylcellulose column, the insulin fraction completely passed through the column, whereas the glucagon fraction was absorbed. The fact that the total apparent biological activity of insulin in the exclusive eluate was higher than in the original extract and the insulin radioimmunoactivity remained unchanged led to the discovery of a potent insulin inhibitor in the extract. The inhibitor was separated from glucagon and insulin in the extract by ion-exchange chromatography on a carboxymethylcellulose column followed by gel filtration on a Bio-Gel P-6 column and finally purified by reverse-phase high-performance liquid chromatography (HPLC) on a C-18 column. The antagonistic effect of this inhibitor on insulin was dose dependent with an ED50 of 2 x 10(-10) M, which was the same level used for insulin in vitro assay (1.7 x 10(-10) M). Amino acid analysis of the inhibitor showed that it was rich in arginine and glycine. It was estimated to be approximately 3000 Mr. The NH2-terminal of the peptide was proved to be blocked because it could not be degraded by Edman degradation. Based on the physicochemical and biochemical characteristics of the inhibitor and compared with other active peptides known to be in the pancreas, the inhibitor is probably a new active peptide that might play an important role in homeostasis of carbohydrate metabolism.
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PMID:Purification and preliminary characterization of new peptide inhibitor of insulin from pork pancreas. 193 26

Since the original description 26 years ago, of the hepatic glycogen synthetase deficiency, only one more case was reported in 1977. We present the studies carried out on an Argentine boy of Italian ancestry who at age 21 months, showed signs of hepatic deficiency with mild clinical symptoms which contrasted with a remarkable fatty liver degeneration. A totally atypic reaction to fructose overload (Table 1, Fig. 1) was the first key to the diagnosis. Glucose levels were not significantly modified by glucagon after 12-hours fasting, but it did increase the glycemia, with decrease of lactate and alanine 3 hours after-meal (Fig. 2a, b). The 24-hours metabolic profile showed fasting hypoglycemia, hyperketonemia, low alanine concentrations and mild lactatemia and hyperglycemia and a net post-prandial increase of lactate (Fig. 3). This profile when reduced to 14 hours, 12-fasting hours and 2-postprandial hours (Fig. 4), revealed similar alterations in an asymptomatic younger brother. The development of the investigation led to a second hepatic biopsy which confirmed hepatic steatosis and to an ultrastructural study, which showed subcellular alterations in the liver and also in muscle (Fig. 5). Moreover low content of hepatic glycogen was observed along with glycogen synthetase activity between 20-25% that of controls, being normal the enzyme activity in muscle and fibroblasts cultured from a skin biopsy (Table 2). The clinical pattern mainly without hypoglycemia, convulsions and/or mental retardation and a normal height and body mass development, allowed us to postulate that this Argentine report would be a mild variant of the disease formerly described and would be correlated with a partial deficiency of the hepatic glycogen synthetase.
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PMID:[Hepatic glycogen synthetase deficiency or glycogen storage disease-zero. Mild phenotype with partial enzymatic defect]. 213 Feb 23

Hyperinsulinemia due to an excessive secretion of insulin independent on normal regulation is the most frequent cause of persistent neonatal hypoglycemia. We report on clinical course, diagnostic procedures and treatment of nesidioblastosis in three patients. Main symptoms observed in newborn period were hypoglycemia, respiratory embarrassment, cyanosis and convulsions. Primary treatment was started by continuous infusion of glucose, administration of diazoxide and prednisolone or glucagon. Most important investigations were performed simultaneously. In all three children subtotal resection of pancreas was necessary, because there was no constant blood glucose level. Histological specimens confirmed diagnosis. In two of three patients pancreatectomy followed. One suffers from diabetes mellitus, the other one fed normally, has stable blood glucose level possibly due to existence of extrapancreatic insulin producing cells.
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PMID:[Clinical aspects, diagnosis and therapy of nesidioblastosis]. 233 45


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