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)

Oral glucose tolerance tests were conducted in 10 noninsulin-dependent diabetic and 14 healthy control subjects with a 75-g glucose load. The tests were repeated 1 week later with 43 g of ethanol mixed with the glucose. Blood samples were analyzed for ethanol, glucose, insulin, C-peptide, and glucagon levels. The blood ethanol peak was nearly equal in diabetic and control subjects (mean +/- SEM values of 55 +/- 8 and 48 +/- 6 mg/dl 45 min after ethanol ingestion). Ethanol did not affect glucose tolerance in either of the study groups. Mean +/- SEM values of the sum of the increment above the baseline glucose level were 659 +/- 48 vs. 675 +/- 76 mg/dl with or without ethanol in diabetics and 227 +/- 35 vs. 244 +/- 36 mg/dl in control subjects. The plasma insulin and C-peptide responses to glucose were delayed in diabetic patients compared to controls but were not affected by ethanol. In vitro, ethanol, at a concentration of 100 mg/dl or greater, significantly decreased insulin binding to erythrocytes in a dose-related manner. Scatchard analysis of competitive insulin binding to erythrocytes indicated that ethanol reduced insulin binding affinity (1.6 +/- 0.5 vs. 4.2 +/- 0.8 x 10(8)/M), but not binding capacity (4.5 +/- 2.4 vs. 4.4 +/- 1.7 nM, with and without ethanol, respectively).
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PMID:Effect of alcohol on glucose tolerance in normal and noninsulin-dependent diabetic subjects. 306 31

The first branch point in gluconeogenesis occurs at the conversion of pyruvate to oxaloacetate. To determine the amount of lactate carbon reaching glucose via the direct pyruvate carboxylase pathway versus the tricarboxylic acid cycle, adult rat hepatocytes in primary culture were incubated for 2 h with one of the following isotopic substrates: [1-14C]lactate, [U-14C]lactate, or [1,2-14C]acetate. Production of 14CO2 and [14C]glucose from each substrate was assessed. The amount of lactate carbon 2 and 3 incorporated into glucose or oxidized to CO2 was determined by subtracting values using [1-14C]lactate from those using [U-14C]lactate. After quantitation of CO2 formed from carbons 2 and 3 of lactate, the amount of these carbons incorporated into glucose via the tricarboxylic acid cycle can be determined by simple proportionality from the ratio of label incorporated into glucose or CO2 from [1,2-14C]acetate. The remaining carbons 2 and 3 of lactate incorporated into glucose are derived from the pyruvate carboxylase pathway directly. Ethanol which on oxidation provides NADH and acetate decreased lactate oxidation and enhanced the pyruvate carboxylase pathway. Glucagon increased carbon flux through both pathways but primarily through the pyruvate carboxylase pathway. In summary, a simple model is presented to examine carbon flux from lactate via the pyruvate carboxylase and tricarboxylic acid pathways during gluconeogenesis.
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PMID:Model to examine pathways of carbon flux from lactate to glucose at the first branch point in gluconeogenesis. 318 10

Acute administration of ethanol increases portal blood flow by 40-60%. This increase in blood flow compensates for the increase in O2 consumption that follows alcohol intake and may play a protective role against hypoxic hepatocellular necrosis. We have investigated the mechanism of this hemodynamic effect of ethanol in the rat using the labeled microsphere technique. We ruled out a direct role of systemic glucagon and of acetaldehyde in mediating the increase in portal flow. However, the increase in flow is maximal at a blood ethanol concentration of 3.5 mM, corresponding to that required to achieve the Vmax of alcohol dehydrogenase, and is suppressed by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Alcohol ingestion results in zonal liver hypoxia and in increases in acetate, both of which have been shown to increase the levels of adenosine, a potent vasodilator, in blood and tissues. Ethanol produces a 400% increase in arterial adenosine. Adenosine infusion leads to a dose-dependent increase in portal blood flow of up to 100%, an effect that is suppressed by administration of 8-phenyltheophylline, an antagonist of adenosine at A1 and A2 receptors. Similarly, the ethanol-induced increase in portal blood flow is fully suppressed by 8-phenyltheophylline. In conclusion, adenosine appears to play an important role in the mechanism by which ethanol increases portal blood flow.
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PMID:New insights on the mechanism of the alcohol-induced increase in portal blood flow. 328 79

In this study we report the effect on splanchnic hemodynamics of acute oral ethanol at doses ranging from 0.25 to 4.0 g/kg body wt. Flows were determined by use of a radioactive microsphere technique. Ethanol was found to increase portal blood flow by 23-57%. In awake rats this increase reached a plateau at the 0.5 g/kg dose. In ketamine-anesthetized rats, the increase was observed only at doses of 3.0 g/kg or more, with the response at doses of 0.5, 1.0, and 2.0 g/kg being suppressed by ketamine. Inhibition of alcohol dehydrogenase by intra-arterial administration of 4-methylpyrazole resulted in suppression of the liver blood flow increase after ethanol was administered to awake animals. Ethanol in the range of doses studied did not result in changes in blood glucagon levels. Rats fed ethanol-containing diets for 4 wk and withdrawn for 18 h had the same response to acute oral ethanol as did naive rats. It is suggested that ethanol metabolism mediates the effects of ethanol on splanchnic blood flow. An increase in splanchnic blood flow when concurrent with an increase in liver O2 consumption induced by ethanol might protect the liver from hypoxic damage.
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PMID:Role of ethanol metabolism in the ethanol-induced increase in splanchnic circulation. 396 96

According to data obtained for different tissues, desensitization of the adenylate cyclase system in the myocardium is a reversible process which can be turned off in vivo with drugs known to decrease the catecholamine level. Contrary to the data obtained in other tissues (1,10,20), we found that resensitization of the myocardial adenylate cyclase system can occur in a simple system containing only plasma membranes and a beta-receptor antagonist. Ethanol, which changes the fluidity of the membrane and may alter the strength of the hydrophobic interactions among the protein components of the cyclase system, as well as dithiothreitol, which affects agonist binding to the beta-adrenergic receptors, can also produce resensitization of adenylate cyclase in vitro. The desensitized state of the beta-adrenergic receptors and adenylate cyclase in a number of tissues is sensitive to guanine nucleotides but not to the antagonist of the hormone (1,10,11,20). In our experiments on the myocardial membrane, we found that preincubation with guanine nucleotides does not change the number of binding sites for the hormone and its antagonist but increases the effect of the antagonist during resensitization of beta receptors. One of the most unusual effects is the hormone-nonspecific desensitization of myocardial adenylate cyclase: in vivo and in vitro desensitization to catecholamines makes the enzyme sensitive to the inhibitory effect of glucagon. The inhibition of basal and guanine nucleotide-activated adenylate cyclase by alprenolol demonstrated that in the myocardium the desensitized beta receptors were able to activate the enzyme. According to data that demonstrate the inhibition of catecholamine-stimulated adenylate cyclase by glucagon, we can interpret the inhibition of desensitized adenylate cyclase by glucagon in terms of competition for the enzyme between the glucagon receptors and desensitized beta-adrenergic receptors. Resensitization of the adenylate cyclase system reduces the activating effect of guanine nucleotides and the inhibitory effect of the antagonist, increases the stimulatory effect of catecholamines, and reverses the inhibitory effect of glucagon on activation. In myocardium as in other tissues (1,10,11,20), resensitization does not change the affinity of the adenylate cyclase system for guanine nucleotides, catecholamines, and their antagonists but increases the binding capacity of the beta-adrenergic receptors in the membranes (9).
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PMID:Regulation of adenylate cyclase by hormones and guanine nucleotides in normal, desensitized, and resensitized rabbit heart. 630 74

Both forskolin and ethanol elicit the activation of basal and ligand-stimulated adenylate cyclase activities in rat liver plasma membranes. Ethanol is most potent at activating the fluoride- and glucagon-stimulated activities whilst having little effect on basal activity. In contrast forskolin exerts its greatest effect on basal activity. Over the concentration range that ethanol activates adenylate cyclase, it also increases bilayer fluidity as indicated by a decrease in the values of the order parameters for an incorporated fatty acid spin probe. At high concentrations forskolin does increase bilayer fluidity. However, it only begins to do so at concentrations above those where forskolin has already exerted its maximal effect in activating adenylate cyclase. Forskolin can still activate, albeit to a reduced extent, detergent-solubilized adenylate cyclase whereas ethanol cannot. Forskolin elicits a pronounced rise in hepatocyte intracellular cyclic AMP concentrations, whereas ethanol does not. Both forskolin and ethanol reduce the temperature of onset of the lipid phase separation occurring in rat liver plasma membranes. This is detected in Arrhenius plots of both glucagon-stimulated adenylate cyclase activity and order parameters of an incorporated fatty acid spin probe, where we find that forskolin is particularly potent in decreasing the temperature at which this lipid phase separation occurs. Our results are consistent with the notion that forskolin exerts its effect on adenylate cyclase primarily by a direct action on the catalytic unit of the enzyme. However, as forskolin is a potent perturber of the organisation of the lipid bilayer it is possible that this could modulate its effect on adenylate cyclase and might be expected to affect the activity of other membrane enzymes.
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PMID:Forskolin and ethanol both perturb the structure of liver plasma membranes and activate adenylate cyclase activity. 630 64

Carbohydrate metabolism has been studied in the offspring of rats fed liquid diet containing ethanol during gestation (EF group). Weight-matched control dams were given liquid diet either by the pair-fed technique (PF group) or ad libitum (AF group). EF and PF dams showed reduced food consumption and attenuated gain in body weight during the gestation period compared with the AF group. Blood glucose, liver glycogen, and plasma insulin levels were significantly reduced in EF and PF dams. Ethanol ingestion resulted in a significant decrease in litter survival and fetal body weight. At term, EF pups on average showed a 30% decrease in blood glucose levels and 40% decrease in plasma insulin levels compared with AF pups. One hour after birth, EF pups exhibited a marked increase in blood sugar level compared with either control group; subsequently, there was a marked decrease in blood glucose levels in EF pups. Liver glycogen stores were significantly reduced in term EF fetuses and were mobilized more rapidly in EF neonates than in either control group. Fetal hyperinsulinemia disappeared shortly after delivery in control pups, as expected; however, in EF pups, the fall in plasma insulin level was gradual. Fetal and neonatal plasma glucagon levels were not altered by ethanol exposure in utero. Blood glucose levels remained significantly low at 2 days of age in EF pups, but reached near control values at 4 days of age. Plasma insulin and glucagon were nearly equal in EF and control pups at 2 and 4 days of age. These results show aberrations in blood glucose, plasma insulin, and liver glycogen levels in offspring exposed to ethanol in utero.
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PMID:Effects of ethanol ingestion on maternal and fetal glucose homeostasis. 637 80

Primary cultures of adult rat hepatocytes were used to study the effects of 100 mM ethanol on various neutral amino acid transport systems. Ethanol exposure for 24 h selectively decreased amino acid uptake by the A and N systems by 40-70%, but had no significant effect on the ASC and L systems. The decrease in the A system was significant after 3 h of ethanol exposure, and the activity was not affected by the presence or absence of ethanol during the uptake measurements. Kinetic analysis showed that ethanol treatment affected predominantly the high-affinity component of A system activity by decreasing the apparent Vmax without significantly changing the apparent Km. Ethanol treatment did not prevent the cells from increasing A system activity in response to insulin and glucagon, but the magnitude of hormone-stimulated uptake was reduced.
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PMID:Ethanol treatment selectively decreases neutral amino acid transport in cultured hepatocytes. 647 6

A case of massive metoprolol poisoning (50 g) is described. Clinical signs included coma, seizures, hypoventilation, unmeasurable blood pressure, nodal bradycardia, and metabolic acidosis. Treatment comprised intubation, assisted ventilation, gastric lavage, atropine, bicarbonate, glucagon and repeated doses of prenalterol (a total of 160 mg over 15 hours). Prenalterol dosage was simple and could be guided by blood pressure response. Pacemaker treatment was not required. Ethanol concentration was 50 mmol/l (2.4%) on admission. Plasma metoprolol was 68 mumol/l (18 000 ng/ml) 2 hours after admission. The patient was awake after 15 hours.
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PMID:Massive metoprolol poisoning treated with prenalterol. 666 32

Effects of glucagon and ethanol on hepatic metabolism were examined with in situ perfused livers from fasted Swiss albino mice. In the absence of added gluconeogenic substrate, the presence of glucagon with ethanol effectively restored hepatic glucose production to a rate found with livers perfused with the hormone alone. When lactate was added to the perfusate, the presence of ethanol almost completely suppressed glucose formation but glucagon only partially overcame this inhibition. Ethanol and/or glucagon inhibited hepatic alpha-amino acid N release both in the absence and presence of added gluconeogenic substrate. Ketone body formation was increased three-fold when both glucagon and ethanol were added together to the medium of livers perfused in the absence of exogenous gluconeogenic precursor, yet neither agent alone had an effect. Ethanol utilization by the perfused liver was markedly inhibited by glucagon in the absence of added lactate. The presence of exogenous lactate also decreased ethanol removal by the liver and the addition of glucagon with lactate diminished ethanol clearance further. Thus, interrelationships between the consequences of glucagon and ethanol on hepatic metabolism have been delineated in the perfused mouse liver.
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PMID:Interrelationships between the metabolic effects of glucagon and ethanol in the perfused mouse liver. 672 2


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