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)

The effect of different thyroid states on the oxidation of free fatty acids was investigated in the isolated perfused liver of 24-h-starved rats. 1. Compared with the euthyroid control the oxidation of oleate to ketone bodies as well as to CO2 was increased in hyper-, while it was unchanged in hypothyroid livers. 2. The addition of carnitine stimulated oleate oxidation in livers from eu- and hyperthyroid rats, but was without effect in hypothyroid livers. 3. Glucose did not affect the thyroid hormone-mediated effect of oleate conversion to ketone bodies. 4. Hepatic oxidation of octanoate was similar in all thyroid states. 5. Re-esterification of oleate was enhanced in hypo-, but reduced in hyperthyroidism. 6. The concentration of hepatic malonyl-CoA was decreased in hypo- and unchanged in hyperthyroid livers. 7. The concentration of cyclic AMP was elevated in the liver of hyperthyroid rats, no differences were observed between eu- and hypothyroid livers. However, increasing the hepatic cyclic AMP content by the addition of glucagon did not stimulate ketogenesis in eu- and hypothyroid livers. 8. The results indicate that thyroid hormones stimulate oleate oxidation by an accelerated transport of its CoA derivative into the mitochondrial compartment.
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PMID:Effect of thyroid state on ketogenic capacity of the isolated perfused liver of starved rats. 627 88

(1) In order to assess the possible role of 3',5'-(cyclic)adenosine monophosphate (cAMP) in the control of glucose transport, the effect of the nucleotide or agents known to increase its intracellular concentration on sugar transport or 45Ca2+ washout were characterized in epididymal fat pads, free fat cells and soleus muscles of the rat. (2) When added to the incubation medium, cAMP (0.1-2.0 mM) stimulated 3-O-[14C]methylglucose washout from fat pads. This effect was abolished by cytochalasin B, and additive to that induced by submaximal (10-25 microU/ml), but not by supramaximal (10 microU/ml) concentrations of insulin. (3) cAMP (2 mM) stimulated the conversion of [U-14C]glucose into CO2 and triacylglycerols. This effect was additive to that of insulin (100 microU/ml). (4) ACTH, glucagon, adrenaline, noradrenaline and salbutamol, which are all known to increase the cAMP content of adipose tissue, stimulated the washout of 3-O-[14C]methylglucose and 45Ca2+ from preloaded fat pads. The fractional losses of the two isotopes were significantly correlated (P less than 0.001, r = 0.73). (5) In free fat cells, adrenaline (10(-6) M) and salbutamol (10(-5) M) stimulated the uptake of 3-O-[14C]methylglucose, and salbutamol (10(-5) M) did not interfere with the stimulating effect of insulin (25 microU/ml) on sugar uptake. (6) In rat soleus muscles, adrenaline and salbutamol produced a dose-dependent stimulation of the washout of 3-O-[14C]methylglucose and 45Ca2+. The effect of adrenaline on sugar efflux was abolished by propranolol. (7) It is concluded that the activation of the glucose transport system by insulin is unlikely to be mediated by a drop in the cellular concentration of cAMP. An increase in cAMP brought about by beta-adrenoceptor agonists or lipolytic hormones may induce a mobilization of calcium ions from cellular pools into the cytoplasm, which in turn leads to the activation of the glucose transport system demonstrated in the present as well as in several earlier studies.
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PMID:The stimulating effect of 3',5'-(cyclic)adenosine monophosphate and lipolytic hormones on 3-O-methylglucose transport and 45Ca2+ release in adipocytes and skeletal muscle of the rat. 629 57

A method is described for measuring rates of mitochondrial pyruvate carboxylation in hepatocytes treated with the polyene antibiotic, filipin, to render the plasma membrane permeable to substrates. With this approach it was possible to demonstrate that treatment of cells with glucagon or catecholamines results in a stimulation of mitochondrial CO2 fixation measured in situ comparable with that observed in the isolated mitochondria, in terms of time of onset of the response, hormone selectivity and sensitivity. In addition, angiotensin II and vasopressin were shown to enhance the activity of pyruvate carboxylase in both the intact mitochondria and filipin-treated cells, thus strengthening the postulate that this site is a major locus of hormone action in the control of gluconeogenesis. Addition of 3-mercaptopicolinic acid, to inhibit gluconeogenesis at the level of phosphoenolpyruvate carboxykinase, had no significant effect on the stimulation of pyruvate carboxylation by adrenaline, suggesting that the effect of the hormone at this site is independent of changes in activity of other enzymes further on in the pathway. The data presented preclude the possibility that acute effects of hormones on mitochondrial metabolism are solely artifacts of the preparation procedure.
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PMID:Hormonal stimulation of mitochondrial pyruvate carboxylation in filipin-treated hepatocytes. 641 Oct 66

Perinatal rat islets of Langerhans, isolated and cultured in vitro, were examined following long-term allotransplantation across a major histocompatibility barrier in nonimmunosuppressed recipients. Islets were isolated to varying degrees of purity without the use of collagenase digestion. Newborn bovine serum was a component of the incubation medium and the atmosphere during culture was air: 5% CO2. Islets transplanted without rigorous purification were fully rejected by 14 days posttransplantation. However, if islets were maintained in subculture, permitting their subsequent meticulous purification, no evidence of rejection was observed after 45 days at the kidney subcapsular site. Grafts consisted of morphologically intact islets. The three major endocrine cell types of the islet were identified by immunocytochemical localization of insulin, glucagon, and somatostatin. These results demonstrate that perinatal islets can exhibit altered immunogenicity, as evidenced by prolonged allograft survival, when isolated and purified by the nonenzymic in vitro method.
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PMID:Modification of allograft immunogenicity in perinatal islets isolated and purified in vitro. 642 93

Glucagon has been shown previously to increase further the enhanced tolerance for hypoxia observed in mice with elevated blood ketones. Glucagon is also known to increase blood glucose and to alter directly the metabolism of some (liver) cells. Both the increase in blood glucose and altered cellular metabolism could contribute to the increase in tolerance for hypoxia observed in mice given glucagon in combination with the ketone, beta-hydroxybutyrate. To evaluate the systemic component of this hypothesis, blood glucose, beta-hydroxybutyrate, and glucagon were elevated alone or simultaneously and hypoxic tolerance of mice was measured. To identify possible cellular effects of glucagon on glucose or ketone metabolism, we measured the incorporation of radiolabeled glucose or beta-hydroxybutyrate into CO2 or total lipid in isolated rat brain slices. Both glucagon and glucose increased hypoxic tolerance of ketotic mice but our data do not support the hypothesis that glucagon's action was only through an elevation of blood glucose. In brain slices glucagon stimulated the incorporation of beta-hydroxybutyrate into CO2 both in the presence or absence of additional glucose. These results demonstrate that glucagon has a direct effect on brain metabolism which may contribute to the increased tolerance for hypoxia. They, however, do not exclude the possibility that glucagon is working in addition to increase hypoxic survival in ketotic mice by increasing the availability of glucose to the brain.
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PMID:Glucagon stimulates ketone utilization by rat brain slices. 642 89

Glucagon induced a rapid (within 3 min) increase in glucose radioactivity and a decrease in the labeling of ketone bodies when isolated hepatocytes were incubated in the presence of [1-14C]palmitate. Simultaneously, the hormone induced a decrease in the levels of pyruvate and Krebs cycle intermediates and an increase in the level of phosphoenolpyruvate (PEP). The glucagon-induced increase in glucose radioactivity was much larger than the simultaneous decrease in lactate labeling. A comparison of the incorporation of labeled carbon from [1-14C]palmitate and [U-14C]palmitate into glucose and CO2 indicates a selective stimulatory action of glucagon on the flux through the phosphoenolpyruvate carboxykinase (PEPCK) reaction.
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PMID:The effect of glucagon on the carbon flux from palmitate into glucose, lactate and ketone bodies, studied with isolated hepatocytes. 646 42

Adaptations of in vitro incorporation of gluconeogenic substrates into glucose and adaptations of metabolite concentrations of liver to subcutaneous phlorizin and dietary 1,3-butanediol were examined for liver samples from dairy steers. Later, the same adaptations were examined after 6 days of feed restriction. Feeding 1,3-butanediol significantly decreased conversion of carbon-14 of lactate and propionate to glucose and to carbon dioxide. There were no changes of concentrations of hepatic glycogen or triglyceride, and increases were only minor for beta-hydroxybutyrate concentration. Both phlorizin, with or without 1,3-butanediol, and feed restriction significantly increased rates of carbon incorporation into glucose from aspartate, lactate, and propionate but did not change rates of oxidation to carbon dioxide. Phlorizin had no effect on hepatic glycogen or triglyceride concentrations, but feed restriction decreased liver glycogen and increased triglyceride concentrations. Changes associated with either phlorizin treatment or feed restriction are consistent with a decreased ratio of insulin to glucagon of blood plasma. When combined, phlorizin and 1,3-butanediol seem to have some utility for developing a ketosis model.
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PMID:In vitro hepatic gluconeogenesis during experimental ketosis produced in steers by 1,3-butanediol and phlorizin. 650 46

Fatty acid synthesis and CO2 production were evaluated in hepatocytes from lean and obese Zucker rats in the presence of 3H2O, and several carbon precursors. The incorporation of 3H2O into fatty acids was greater in obese compared to lean rats in both the isolated hepatocyte and in vivo. The rates of incorporation of 3H2O into fatty acids and cholesterol in hepatocytes of both lean and obese rats were linear for 2 hr, in the absence or presence of 16.7 mM glucose. Rates of fatty acid synthesis were higher in the presence of 16.7 mM glucose compared to the absence of glucose in both lean and obese while rates of cholesterol synthesis were similar. The incorporation of 3H2O into fatty acids, but not into cholesterol, was correlated with increasing glucose concentration and was 2 to three-fold higher in hepatocytes of obese compared to lean rats in the presence of several carbon precursors. Differences in CO2 production between lean and obese rats suggested increased pentose phosphate shunt activity, decreased pyruvate dehydrogenase activity, and lower tricarboxylic acid cycle activity in obese rats. Fatty acid synthesis and CO2 production from 3H2O and [U-14C]glucose in hepatocytes of lean and obese rats was similarly elevated by insulin and depressed by glucagon at several concentrations, suggesting that hepatocytes of obese animals respond to these hormones. These data indicate that rates of hepatic fatty acid synthesis although higher in obese rats respond to modulation in a fashion which is similar to the response in lean rats. The present studies suggest that the oxidation of several carbon precursors in the tricarboxylic acid cycle is diminished in obese compared to lean rats, but pentose phosphate shunt activity is greater in the obese Zucker rats.
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PMID:Regulation of lipid synthesis in hepatocytes from lean and obese Zucker rats. 679 6

Ketone body production and oxidation of 14C fatty acids to CO2 were measured in hepatocytes isolated from lean and obese Zucker rats. The oxidation of [1-14C]octanoate, [1-14C]palmitate and [1-14C]palmitoyl carnitine to 14CO2 was 50%--70% less in obese than in lean rats. Although ketone body production in hepatocytes from both lean and obese rats was increased by fasting, there was a significantly lower rate of ketone body production in hepatocytes from obese rats. Ketone body production was reduced to a comparable extent by increasing the glucose concentration in the incubation media of hepatocytes from both lean and obese rats. Glucagon and carnitine increased ketogenesis and the effect were additive and similar in lean and obese rats. These data suggest that beta-oxidation and ketogenesis are suppressed in the obese Zucker rat, and further that ketone bodies can be modulated similarly in hepatocytes from lean and obese rats by nutritional and hormonal intervention. It is postulated that the decreased beta-oxidation and ketone body production may play a role in the development or maintenance of obesity in the Zucker rat.
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PMID:Oxidation and ketogenesis in hepatocytes of lean and obese Zucker rats. 680 48

The uptake and metabolism of [1-14C]oleate (0.3 mmol/L) were studied in isolated hepatocytes from lean and obese Zucker rats fed either a control (low-fat) diet or a high-fat diet. With the control diet, [1-14C]oleate uptake was increased by 70% in the obese rats, and fat-feeding decreased this uptake to values comparable to that of their lean littermates. Interestingly, the hepatocyte mean surface area was increased in the obese mutants by 21% with the control diet and by 30% with the high-fat diet. The possible reasons for the differences in oleate uptake are discussed. With the control diet, cells from the obese rats showed a four-fold rise in [1-14C]oleate esterification, while ketogenesis (beta-hydroxybutyrate + acetoacetate production) as well as the radioactive acid-soluble products were greatly depressed. Production of CO2 was very low and similar in both groups of animals. Adaptation to the high-fat diet in the obese rats resulted in a reversal between esterification and oxidation of oleate: the latter became the major metabolic pathway as in the lean rats. The ketogenic capacity was greatly if not completely restored. In the lean animals, glucagon stimulated ketogenesis both in the presence or absence of oleate and decreased [1-14C]oleate esterification. In the obese rats, the hormone exerted a significant ketogenic effect only if oleate was present and did not influence its esterification. The data demonstrate the following abnormalities in the hepatocytes of obese Zucker rats: (1) an enlargement of cell size, (2) an increased oleate uptake, (3) a virtual absence of a ketogenic response to exogenous oleate, and (4) a markedly increased esterification of the latter. The metabolic defects, but not the cell size, appear to be largely corrected by an adaptation to a high-fat diet. The hepatic response to glucagon was decreased in the obese rats at the level of endogenous ketogenesis.
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PMID:Oleate metabolism in isolated hepatocytes from lean and obese Zucker rats. Influence of a high fat diet and in vitro response to glucagon. 686 56


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