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)

Epinephrine caused hyperglycemia in part by increasing gluconeogenesis. However, the mechanism of its gluconeogenic effects has not been studied in ruminants. This study was undertaken to examine the effect of epinephrine on the net hepatic uptake of selected glucose precursors in sheep. The major abdominal blood vessels of the sheep were catheterized in normal and alloxan diabetic sheep. Glucose production, metabolic clearance of glucose, and the hepatic removal of certain glucose precursors were determined before, during, and after epinephrine infusion. Epinephrine increased the hepatic glucose output, the concentrations of lactate and glycerol in plasma, and the net hepatic uptake and fractional hepatic extraction of lactate and glycerol. These effects were independent of changes in the concentrations of insulin and glucagon in plasma. These results show that epinephrine directly stimulates hepatic gluconeogenesis in sheep.
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PMID:Effects of epinephrine on the net hepatic uptake of lactate, pyruvate, and glycerol in sheep. 205 10

The effect of a long-acting somatostatin analogue on the acute renal hypertrophy following induction of experimental diabetes in the rat has been studied. The kidney weight increase occurring at 2 and 7 days after alloxan injection was significantly lower in the diabetic group receiving somatostatin. Similarly, the previously reported increase in glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) found in the kidney at 2 and 7 days of diabetes was less marked in the group receiving SMS 201-995. The fall in renal phosphoribosyl pyrophosphate associated with early diabetic renal hypertrophy (7) was also lessened by administration of SMS 201-995. No effects of the drug were found in the normal rat on the same regimen of treatment. These observations indicate involvement of glucagon and/or growth hormone in the initiation of kidney growth in diabetes.
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PMID:The effect of a somatostatin analogue (SMS 201-995, Sandostatin) on the concentration of phosphoribosyl pyrophosphate and the activity of the pentose phosphate pathway in the early renal hypertrophy of experimental diabetes in the rat. 245 25

Insulin-like growth factor I (IGF-I, somatomedin C) was mapped by immunocytochemistry in the pancreas of normal and experimentally influenced rats. The polyclonal IGF-I antiserum K 37 was characterized and demonstrated to be specific. In the exocrine pancreas some duct cells showed IGF-I immunoreactivity, other components being negative. The three main endocrine cell types in the islets of Langerhans were IGF-I immunoreactive, most strikingly the D cells. Hypophysectomy resulted in loss of IGF-I immunoreactivity in all three endocrine cell types, i.e. D, A and B cells, while the levels of somatostatin, glucagon and insulin, respectively, remained unchanged. Starvation seemed to increase and feeding to decrease the IGF-I immunoreactivity in the B cells. Cysteamine pre-treatment reduced the normally intense IGF-I and somatostatin immunoreactivities in the D cells. In rats made diabetic with alloxan or streptozotocin, the B cells were irreversibly damaged and lost both their insulin and IGF-I immunoreactivities, while the IGF-I immunoreactivity was increased in A cells; the D cells remained unchanged. The concentrations of IGF-I mRNA in the pancreas were almost equal in normal and alloxan diabetic rats as were the concentrations of extractable IGF-I. We conclude that IGF-I immunoreactive material can be demonstrated in adult animals in all endocrine islet cells, most prominently in the D cells. The expression of IGF-I immunoreactivity is in part under pituitary control. In the adult rat only one islet cell type synthesizes IGF-I immunoreactive material, i.e. the D cells, while, in contrast, the B cells are likely to be a major IGF-I source in fetal and neonatal islets.
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PMID:Insulin-like growth factor I in the pancreas of normal and diabetic adult rats. 246 68

We studied the lipase and colipase activity in pancreatic acinar tissue of insulin-deficiency and insulin-resistance obese Zucker rats (fa/fa). After injection of streptozotocin (STX 75 mg/kg) in normal Sprague-Dawley rats, the activity of lipase and colipase in pancreatic acinar tissue was increased by approximately 100%, the increase in colipase occurring 3 days later than that of lipase. At the same time, the amylase activity was decreased by 98%. Injection of alloxan (125 mg/kg) induced a similar change of pancreatic enzyme pattern, with amylase activity strongly reduced by 79% and activity of lipase and colipase increased 20.5 and 18.6%, respectively. Correction of the diabetic state with insulin (1 U/100 g/day) reversed the activity of these enzymes to their prediabetic levels. Administration of insulin (6 U/100 g/day) to normal Sprague-Dawley rats increased the activity of amylase as well as lipase and colipase, whereas injection of glucagon (0.3 mg/100 g/day) decreased the activity of amylase and colipase but had no significant effect on lipase activity. In the obese Zucker rats (fa/fa), the activity of lipase and colipase at onset of obesity (5 weeks of age) was lower than that in their lean littermates (fa/o). Thereafter the activity of the two proteins increased with age, being 40% higher in the fa/fa rat than in the fa/o rat at age 7 weeks. During the same period, amylase activity decreased. These results indicate that pancreatic lipase and colipase activity are increased following either insulin deficiency or insulin resistance in rats by a mechanism related to the changed levels of insulin.
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PMID:Pancreatic lipase and colipase activity increase in pancreatic acinar tissue of diabetic rats. 247 69

The insulin release from isolated pancreatic islets grafted under the kidney capsule was examined by means of a modified kidney-perfusion technique. The grafts, consisting of 150 C57BL/6 or 250 C57BL/Ks mouse islets, were implanted syngeneically under the left kidney capsule of normoglycemic or alloxan-induced diabetic recipients 4 wk before the perfusion. In both mouse strains, islets grafted to normoglycemic animals showed an immediate distinct peak of insulin release when challenged with high glucose, whereas no response was observed from islets grafted to hyperglycemic mice. In a similar way in C57BL/Ks mice, arginine stimulated insulin release from the islet grafts in normoglycemic but not in hyperglycemic recipients. Insulin treatment of the diabetic recipients, however, partially normalized the insulin response to glucose. Islet grafts were removed in toto and analyzed for contents of insulin, glucagon, somatostatin, and DNA or rates of glucose-stimulated (pro)insulin biosynthesis. In both mouse strains, islets implanted into hyperglycemic animals contained significantly less insulin, and their rates of (pro)insulin biosynthesis were markedly decreased. Insulin treatment only marginally affected these parameters. The glucagon content of the grafted islets was unaffected by the hyperglycemia in both strains of mice, whereas a significant decrease in the somatostatin content was observed in the C57BL/Ks mice. We concluded that grafted islets exposed to prolonged hyperglycemic stress become functionally impaired in mice of both strains. Our perfusion technique of islet-graft-bearing kidneys in combination with biochemical studies on the removed grafts provides a suitable model for studies of the effects of prolonged hyperglycemia on islet beta-cell function.
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PMID:Effects of hyperglycemia on function of isolated mouse pancreatic islets transplanted under kidney capsule. 249 93

Compounds with a reported in vivo and in vitro effect on the diabetogenicity of alloxan were studied with regard to the uptake of calcium in mouse islet mitochondria, with the aim of obtaining information on the susceptibility and selectivity of alloxan toxicity. A strong correlation was found between the uptake of calcium in mouse islet mitochondria, which is believed to be associated with the activation of oxidative enzymes involved in energy production and secretion of insulin, and the protection afforded by the injection of D-glucose, D-mannose, L-leucine and glucagon, and by the in vitro administration of cyclic AMP, L-glutamine and L-leucine. The effect of D-glucose was abolished by D-mannoheptulose. A correlation was also seen between reduced mitochondrial uptake of calcium and the potentiation of alloxan cytotoxicity afforded by 1.25-dihydroxycholecalciferol, methylene blue and menadione. The observations suggest an association between functional activity and alloxan cytotoxicity. The selectivity of the cytotoxic action of alloxan is believed to be dependent on a reduced mitochondrial uptake of calcium and an associated reduction of the energy production at low functional activity in the B-cells (e.g. in starvation which is well-known to potentiate the alloxan effect).
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PMID:Alloxan diabetogenicity: determinants of potentiation, protection and B-cell selectivity. 254 7

Hepatocyte membranes from both lean and obese Zucker rats exhibited adenylate cyclase activity that could be stimulated by glucagon, forskolin, NaF and elevated concentrations of p[NH]ppG. In membranes from lean animals, functional Gi was detected by the ability of low concentrations of p[NH]ppG to inhibit forskolin-activated adenylate cyclase. This activity was abolished by treatment of hepatocytes with either pertussis toxin or the phorbol ester TPA, prior to making membranes for assay of adenylate cyclase activity. In hepatocyte membranes from obese animals no functional Gi activity was detected. Quantitative immunoblotting, using an antibody able to detect the alpha subunit of Gi, showed that hepatocyte plasma membranes from both lean and obese Zucker rats had similar amounts of Gi-alpha subunit. This was 6.2 pmol/mg plasma membrane for lean and 6.5 pmol/mg plasma membrane for obese animals. Using thiol pre-activated pertussis toxin and [32P]-NAD+, similar degrees of labelling of the 40 kDa alpha subunit of Gi were found using plasma membranes of both lean and obese Zucker rats. We suggest that liver plasma membranes from obese Zucker rats express an inactive Gi alpha subunit. Thus lesions in liver Gi functioning are seen in insulin-resistant obese rats and in alloxan- and streptozotocin-induced diabetic rats which also show resistance as regards the acute actions of insulin. Liver plasma membranes of obese animals also showed an impairment in the coupling of glucagon receptors to Gs-controlled adenylate cyclase, with the Kd values for activation by glucagon being 17.3 and 126 nM for lean and obese animals respectively. Membranes from obese animals also showed a reduced ability for high concentration of p[NH]ppG to activate adenylate cyclase. The use of [32P]-NAD+ and thiol-preactivated cholera toxin to label the 43 kDa and 52 kDa forms of the alpha-subunit of Gs showed that a reduced labelling occurred using liver plasma membranes from obese animals. It is suggested that abnormalities in the levels of expression of primarily the 52 kDa form of alpha-Gs may give rise to the abnormal coupling between glucagon receptors and adenylate cyclase in liver membranes from obese (fa/fa) Zucker rats.
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PMID:Multiple defects occur in the guanine nucleotide regulatory protein system in liver plasma membranes of obese (fa/fa) but not lean (Fa/Fa) Zucker rats: loss of functional Gi and abnormal Gs function. 256 40

Experiments on mice and rats with alloxan diabetes were conducted for comparative assessment of the effectiveness of therapeutic use of adaptogenic plant pharmaceuticals as well as some other commonly used plant drugs. Of marked antidiabetic properties were root and leaf ginseng tincture (LGT), Echinopanax tincture, extracts of Eleutherococcus, Rhodiola (ER) and Leuzia which decreased the blood level of glucose in a CTT (5 g h of glucose per I kg of the animal body mass) from 17.15 to 11.19, 11.50, 12.72, 11.69, 13.47 mmol/l and increased the alloxan-reduced level of liver glycogen by 50-80% (P less than 0.05). Aralia and Schizandra tinctures for this diabetic model were ineffective. Yarrow, everlastings and birch leaf tea also possessed marked hypoglycemic and glycogen sparing properties. The most effective experimentally plant adaptogens LGT and ER increased the blood level of insulin in alloxan diabetic rats in a GTT from 16.75 up to 44.42, 35.31 microU/ml and decreased the level of glucagon from 495 to 195 and 138 pg/ml, respectively. The authors discussed mechanisms of antidiabetic, insulinotropic and hypoglucagonemic action of the effective plant pharmaceuticals and the prospects of their use in multimodality therapy of diabetes mellitus of type I.
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PMID:[The action of adaptogenic plant preparations in experimental alloxan diabetes]. 262 92

The plasma concentration of glucagon (IRG), catecholamines, and hepatic glucose production (Ra) were followed in insulin-induced hypoglycemia in dogs before (normal) and at 14-21 and again at 89-119 days after the injection of alloxan (diabetic). Some diabetic dogs were also tested when euglycemia was restored by phlorizin. In the normal state plasma IRG and epinephrine were raised by a factor of 3 and 15, respectively. Ra increased in two phases, an early peak (350% basal) was followed by a plataeu at about twice basal. In diabetes, irrespective of its duration, plasma IRG was decreased in hypoglycemia, and the rise in plasma epinephrine was significantly reduced. Ra remained unchanged. In phlorizin-treated euglycemic diabetic dogs plasma IRG fell, and the response in plasma epinephrine remained blunted. There was no early rise in Ra, but the same elevated plateau was reached at the same time as in normal animals. In conclusion, the following is observed in diabetic dogs. 1) The sensitivity of alpha-cells to insulin is maintained, but that to hypoglycemia is lost. The concentration of plasma catecholamines is raised less than in normals. With no increase in plasma glucagon this rise is not sufficient to increase Ra. 2) Restoration of euglycemia with phlorizin does not restore normal IRG and epinephrine responses to hypoglycemia but restores the delayed increase of Ra. Thus the restoration of euglycemia in severely diabetic dogs partially restores the responses of the liver, but not of the alpha-cell or sympathetic discharge, to hypoglycemia.
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PMID:Phlorizin-induced normoglycemia partially restores glucoregulation in diabetic dogs. 264 87

Diabetes mellitus was acutely produced in nine pregnant sheep by the intravenous administration of alloxan 40 mg/kg in the maternal inferior vena cava. Maternal and fetal plasma concentrations of glucose, lactate, beta-hydroxybutyrate, insulin, glucagon, and PaO2, oxygen content, and pH were determined before and at days 1, 3, and 5 after the injection of alloxan. Two animals aborted between days 1 and 3 after alloxan administration. In the other animals, significant changes occurred from baseline to day 5: maternal hyperglycemia (56.8 +/- 5.2 vs. 227.3 +/- 54.6 mg/dl; p less than 0.01), maternal hypoinsulinemia (6.2 +/- 3.5 vs. 1.0 +/- 0.4 microU/ml, p = 0.016); maternal hyperketonemia (beta-hydroxybutyrate: 0.79 +/- 0.27 vs. 4.69 +/- 2.64 mmol/L, p less than 0.01); fetal hyperglycemia (17.0 +/- 2.6 vs. 86.0 +/- 16.2 mg/dl, p less than 0.001); fetal hyperinsulinemia (8.4 +/- 4.5 vs. 19.2 +/- 6.4 microU/ml, p less than 0.001); fetal hyperketonemia (beta-hydroxybutyrate: 0.03 +/- 0.03 vs. 0.06 +/- 0.02 mmol/L, p less than 0.05); fetal hypoxemia (arterial PO2: 21.6 +/- 1.8 vs. 18.0 +/- 2.8 mm Hg, p less than 0.05, and oxygen content: 7.1 +/- 0.5 vs. 4.5 +/- 1.9 vol/dl, p less than 0.02). Thus alloxan administered in the pregnant ewe can produce major metabolic and endocrine derangements acutely simulating those occurring in human insulin-dependent diabetic pregnancy.
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PMID:Alloxan-induced diabetes mellitus in the pregnant ewe: metabolic and cardiovascular effects on the mother and her fetus. 265 13


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