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)

Alloxan diabetic rats maintained on protamine zinc insulin for two weeks were used for these studies. Hepatocytes were isolated from these rats at various time intervals after withdrawal of insulin (0, 48, 72 and 96 hr). Gluconeogenesis with various concentrations of lactate and fructose was studied. Both lactate and fructose stimulated gluconeogenesis and showed progressive increases in glucose production up to 72 hr after the insulin withdrawal. Glucose production decreased at 96 hr. Protein synthesis in isolated hepatocytes from diabetic liver cells, as measured by the incorporation of radioactive isoleucine, valine and phenylalanine into protein, showed a decrease (5- to 6-fold) with time after insulin withdrawal. Glucagon (10(-6)M) alone increased cyclic AMP levels 10-fold in liver cells, in isolated cells from rats maintained on insulin (0 hr) or from rats withdrawn from insulin for 48 hr. The ability of glucagon to elevate cyclic AMP levels in isolated diabetic liver cells decreases 72 hr following insulin withdrawal.
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PMID:Studies on gluconeogenesis, protein synthesis and cyclic AMP levels in isolated hepatocytes from alloxan diabetic rats. 17 99

Isloated rat islets were maintained in vitro in a perifusion system, exposed to alloxan (20 mg/100 ml) for 5 minutes in the presence of agents which affect cAMP metabolism and subsequently stimulated with glucose. The rate of insulin secretion was monitored throughout the period of perifusion. Exposure to alloxan alone produces complete inhibition of glucose-induced insulin release [18] whereas concomitant exposure to carreine and theophylline for this brief interval provided almost complete protection of the islets from the inhibitory action of alloxan. Glucagon, cAMP and CBcAMP did not protect the islets form alloxan. Pre-treatment of the islets with either theophylline or glucagon and DBcAMP did not provide protection. These findings indicate that the protective action of theophylline and carreine against alloxan is unrelated to the effect of these agents on cAMP metabolism in the beta cell.
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PMID:Effect of methylxanthines on alloxan inhibition of insulin release. 17 10

1. The development of glycerolkinase before and after birth was investigated in liver and kidney of rat and hamster. In rat liver, enzyme activity increased very slowly before birth and rapidly thereafter, reaching adult values at the 6th day of postnatal life. In hamster liver, glycerolkinase was considerably elevated already in utero, increased dramatically within the 1st day of postnatal life and reached adult values at the end of the 1st week. The development of hepatic glycerolkinase was compared with that of hepatic phosphoenolpyruvate carboxykinase of rat and hamster up to the 20th day of postnatal life. The different time-courses of the levels of these two enzymes before and after birth as well as the known kinetics of serum insulin, glucagon and corticosterone during that time suggested that none of these hormones is involved in the perinatal development of hepatic glycerolkinase activity. In contrast to liver, kidney glycerolkinase activity in both, rat and hamster, showed a delayed increase during the first week of postnatal life followed by a more pronounced elevation to adult values within the following 2 weeks. 2. When liver and kidney glycerolkinase activity was investigated during starvation (+/- refeeding), in alloxan diabetes(+/- insulin) and after adrenalectomy (+/- cortisol) no significant change in enzyme activity per g tissue could be detected either in liver or in kidney. However, total hepatic glycerolkinase activity was diminished during starvation as a consequence of decreasing liver weight. 3. Incorporation of U-[14C]-glycerol into CO2, lipids and glucose + glycogen by rat liver and kidney cortex slices was studied under the above gluconeogenetic conditions. Despite unchanged glycerolkinase activity in both organs, gluconeogenesis from glycerol was enhanced during starvation and in chronic alloxan diabetes, and could be reversed by refeeding and insulin replacement, respectively. 4. Feeding 20% of linolic acid to normal, alloxan-diabetic or adrenalectomized rats resulted in a significant increase in glycerolkinase activity in liver but not in kidney. 5. From the present findings it is suggested that the first step of gluconeogenesis from glycerol in liver and kidney is not influenced by glucagon, insulin and glucocorticoids, which are generally believed to regulate the rate of gluconeogenesis from non-glycerol precursors, but probably by the change in blood glycerol concentration.
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PMID:Glycerolkinase--a regulatory enzyme of gluconeogenesis? 18 91

Normal male rats were made chronically diabetic by injection of alloxan or acutely diabetic by injection of anti-insulin serum. The concentration of cyclic AMP in epididymal adipose tissue was increased approximately 2 1/2-fold 24 h after alloxan administration and up to 7-fold 72 h post-alloxan. Treatment of alloxan-diabetic rats with insulin for 4 h completely suppressed lipolysis but only partially suppressed cyclic AMP levels; 6 h following insulin treatment cyclic AMP levels were normal. When segments of the epididymal fat bodies were incubated in vitro the high cyclic AMP levels were not maintained but instead decreased spontaneously. Addition of insulin to the incubation media decreased lipolysis in tissues of diabetic rats to levels measured in tissues of normal rats and accelerated the decline in cyclic AMP levels but did not return cyclic AMP levels to normal. Rats rendered acutely insulin deficient by injection of anti-insulin serum showed increased plasma glucose and free fatty acid levels and increased adipose tissue free fatty acid, and cyclic AMP levels 30 min following injection of the antiserum. Plasma glucagon levels increased but not until 2 h following anti-insulin serum, thereby excluding the possibility that an increment in plasma glucagon is the primary stimulus for the acceleration of lipolysis in diabetes. These data are consistent with the view that control of adipose tissue cyclic AMP levels in situ is an important physiologic action of insulin.
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PMID:Adenosine 3',5'cyclic monophosphate in adipose tissue of diabetic rats. 18 24

Liver protein kinase was determined in the absence and presence of cAMP4. Experimental alloxan diabetes resulted in a decrease in total protein kinase (+cAMP) and an increase in the activity ratio (-cAMP) divided by (+cAMP) in liver. Insulin treatment of diabetic rats reversed the observed changes in protein kinase in liver. Glucagon administered in vivo to normal rats caused an increase in the activity ratio and a decrease in total protein kinase activity in liver. The changes are similar to those in diabetes. A decrease in the ratio of insulin to glucagon in diabetes may account for the changes in protein kinase observed.
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PMID:Effect of experimental diabetes and glucagon on cAMP-dependent protein kinase in rat liver. 19 20

Ketotic, insulin-requiring diabetes mellitus and a severe peripheral neuropathy developed in a previously healthy 25-year-old man several days after he attempted suicide with rat poison containing N-3-pyridylmethyl N'-p-nitrophenyl urea. Study of islet-cell function ten months after ingestion showed a reduced disappearance rate of intravenous glucose and depressed C-peptide response to intravenous glucose when compared with a normal control but no impairment of glucagon release after intravenous arginine stimulation. Nerve conduction studies demonstrated severe sensory and mild motor neuropathy. Quadriceps capillary basement membrane thickness was in the diabetic range. Because at least 15 similar occurrences have been reported to the manufacturer, this agent appears to be diabetogenic in man, probably causing beta-cell destruction. Niacinamide, which can prevent glucose intolerance in both streptozocin- and alloxan-treated animals and prevents death in rats given this rodenticide, may be a useful antidote.
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PMID:Diabetes mellitus following rodenticide ingestion in man. 20 29

Venous blood returning from the splanchnic viscera has liver-supporting (hepatotrophic) qualities not found to the same degree in other kinds of arterial or venous blood. The effects of portal blood have been noted in animals with two livers (or a differential portal blood supply to different regions of one liver) to include hypertrophy, glycogen storage, hyperplasia, capacity for regeneration, increase of several synthetic functions, and maintenance of normal structure. The main splanchnic venous hepatotrophic factors are endogenous hormones of which the single most important is insulin. Thus, the foregoing portal hepatotrophic effects are largely eliminated with the diabetes produced by alloxan or total pancreatectomy. The injury of portacaval shunt is caused by the diversion of the hormones around the liver. Accordingly, the atrophy, injury to the organelles, and loss of the capacity for cell renewal is minimized if insulin is infused into the portally deprived liver. In these and other experiments, exogenous glucagon alone or the addition of glucagon to insulin has had no effect, but this may be because of the masking presence of gut glucagon and other hormonal or non-hormonal substances in our models. At present, the effects on the liver of exogenous insulin, glucagon, epidermal growth factor, and numerous other hormones are being determined by their intraportal infusion into eviscerated dogs in which other endogenous splanchnic factors have been eliminated.
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PMID:A hundred years of the hepatotrophic controversy. 20 94

The hepatic cysteine dioxygenase activity of rats was markedly decreased by the intraperitoneal administration of glucagon. The enzyme activity was also decreased by either dibutyryl cyclic AMP or theophylline. The prior administration of actinomycin D completely blocked the glucagon-mediated decrease of enzyme activity, while administrations of this inhibitor of protein synthesis after glucagon injection did not block the decrease of enzyme activity. A single administration of actinomycin D resulted in a slight increase of cysteine dioxygenase activity in the rat liver. On the other hand, the injection of cycloheximide resulted in a rapid decrease of the hepatic cysteine dioxygenase with a half-life of 2.5 h. The half-life of the enzyme in rat liver after glucagon administration was one hour. The administration of hydrocortisone or insulin had no effect on the glucagon-mediated decrease of cysteine dioxygenase of rat liver. The enzyme activity of alloxan diabetic rat liver was almost the same as that of the intact rat liver. The evidence obtained here suggests that enhancement of degradation or inactivation of cysteine dioxygenase is responsible for the glucagon-mediated decrease of the enzyme activity in rat liver.
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PMID:Decrease of rat liver cysteine dioxygenase (cysteine oxidase) activity mediated by glucagon. 21 16

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.
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PMID:Glucose and 3-O-methylglucose protection against alloxan poisoning of pancreatic alpha and beta cells. 33 68

The pancreatic insulin-, glucagon-, and somatostatin-positive cell populations were quantitated in normal and alloxan-diabetic rats. The method of quantitation (linear scanning) allowed an estimation of absolute changes in these cell populations through 14 months of diabetes. The changes in cell masses were correlated with changes in plasma and pancreatic immunoreactive insulin and glucagon. A marked reduction in the insulin-positive beta cells was demonstrated within seven days after alloxan treatment. No significant change in the glucagon-positive alpha cell population was noted in the diabetic rats when compared with normoglycemic controls. A statistically significant increase in the pancreatic somatostatin-positive delta cell population was demonstrable only after 14 months of alloxan diabetes. The results would suggest that the hyperglucagonemia of insulin-deficient diabetes is not a consequence of an increased pancreatic alpha cell population. In addition, since the increase in the pancreatic delta cell mass was found only late in the course of alloxan diabetes in the rat, the increase in delta cells is probably not of significance in the pathophysiology of diabetes in this experimental model.
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PMID:Morphometric quantitation of the pancreatic insulin-, glucagon-, and somatostatin-positive cell populations in normal and alloxan-diabetic rats. 33 4


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