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)

1,3-Butanediol is an ethanol dimer that induces systemic ketosis. It has previously been shown to increase hypoxic survival time and reduce neurologic deficit in several experimental preparations. The aim of this study was to determine if the mechanism of 1,3-butanediol-induced cerebral protection was elevation of blood ketone levels, blood glucagon levels, or both. Blood beta-hydroxybutyrate levels, glucagon levels, or both produced by a previously reported protective dose of 1,3-butanediol (47 mmol/kg) were simulated by direct i.v. infusion of the ketone beta-hydroxybutyrate and glucagon separately and in combination, and the effect on hypoxic survival time in instrumented Levine rats (unilateral carotid ligation and hypoxic exposure) was determined. To test if the mechanism was a direct or osmotic effect of the alcohol, an equimolar dose of ethanol (47 mmol/kg) was administered and the effect on hypoxic survival time was compared with that produced by 1,3-butanediol. As in previous studies, 1,3-butanediol significantly increased hypoxic survival time (241% of control, Scheffe p less than 0.05). Various doses of beta-hydroxybutyrate and glucagon were infused to approximate the blood levels of beta-hydroxybutyrate and glucagon produced by a protective dose of 1,3-butanediol. Although beta-hydroxybutyrate or glucagon infusions produced blood levels of these substances that were comparable with those produced by administering butanediol, they failed to prolong hypoxic survival time as long as 1,3-butanediol. No correlation was detected between hypoxic survival time and blood levels of beta-hydroxybutyrate, glucagon, insulin, or glucose. An equimolar dose of ethanol did not significantly increase hypoxic survival time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevated blood ketone and glucagon levels cannot account for 1,3-butanediol induced cerebral protection in the Levine rat. 381 Jul 56

The hyperglycemia and ketosis of diabetes mellitus are generally associated with elevated levels of glucagon in the blood. This suggests that glucagon is a contributing factor in the metabolic abnormalities of diabetes mellitus. A glucagon-receptor antagonist might provide important evidence for glucagons's role in this disease. In this work we describe how we combined structural modifications that led to glucagon analogues with partial agonist activity to give glucagon analogues that can act as competitive antagonists of glucagon-stimulated adenylate cyclase activity. Using solid-phase synthesis methodology and preparative reverse-phase high-performance liquid chromatography, we synthesized the following seven glucagon analogues and obtained them in high purity: [D-Phe4,Tyr5,Arg12]glucagon (2); [D-Phe4,Tyr5,Lys17,18]glucagon (3); [Phe1,Glu3,Lys17,18]glucagon (4); [Glu3,Val5,Lys17,18]glucagon (5); [Asp3,D-Phe4,Ser5,Lys17,18]glucagon (6); I4-[Asp3,D-Phe4,Ser5,Lys17,18]glucagon (7); [Pro3]glucagon (8). Purity was assessed by enzymatic total hydrolysis, by chymotryptic peptide mapping, and by reverse-phase high-performance liquid chromatography. The new analogues were tested for specific binding, for their effect on the adenylate cyclase activity in rat liver membranes, and for their effect on the blood glucose levels in normal rats relative to glucagon. Analogues showing no adenylate cyclase activity were examined for their ability to act as antagonists by displacing glucagon-stimulated adenylate cyclase dose-response curves to the right (higher concentrations). The binding potencies of the new analogues relative to glucagon (= 100) were respectively 1.0 (2), 1.3 (3), 3.8 (4), 0.4 (5), 1.3 (6), 5.3 (7), and 3 (8). Glucagon analogues 3-5 and 8 were all weak partial agonists with EC50 values of 500 (3), 250 (4), 1600 (5), and 395 nM (8), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Design and synthesis of glucagon partial agonists and antagonists. 381 83

This study examined ketosis in response to 90 min of running before and after the ingestion of 50 g glucose or 50 g L-alanine in thirty-three athletes. Everyone ran 20 km at 07.30 h and then rested, while fasting, till 16.00 h. There were four test groups: 'glucose-before', 'glucose-after', 'alanine-before' and 'alanine-after' according to whether glucose or alanine was ingested at 07.00 h, or 09.00 h. Controls did not ingest either test substance. The control 3-hydroxybutyrate concentration rose from 0.23 +/- 0.03 mmol/l (S.E. of mean) at 07.00 h to 0.74 +/- 0.27 mmol/l at 12.00 h, and 0.94 +/- 0.33 mmol/l at 16.00 h. Glucose ingestion before or after exercise did not influence post-exercise ketosis significantly, despite high insulin: glucagon ratios, low free fatty acid concentrations and hyperglycaemia. Alanine significantly lowered the 3-hydroxybutyrate levels, especially after exercise (to 0.14 +/- 0.07 mmol/l at 12.00 h; P less than 0.05) despite reversed insulin: glucagon ratios. This suggests that hepatic responsiveness to portal hyperglycaemia and the main hormones of metabolism is altered immediately after exercise, presumably to promote muscle glycogen synthesis in preference to liver glycogen synthesis.
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PMID:Post-exercise ketosis in post-prandial exercise: effect of glucose and alanine ingestion in humans. 388 75

Six Holstein cows were sampled hourly for 24 h for plasma concentrations of hormones and metabolites. Cows were sampled at about 2 wk prepartum, at 3 wk postpartum, during a ketonemia induced by feed restriction to 54% of ad libitum intake, and after a recovery period. They were fed long alfalfa hay postpartum. The onset of lactation caused concentrations of growth hormone, glucagon, acetoacetate, beta-hydroxybutyrate, and total amino acids of plasma to increase and those of glucose and insulin to decrease. Feed restriction exacerbated changes at 3 wk postpartum except for total amino acids and glucagon, which both decreased to prepartal concentrations. Resumption of ad libitum feeding caused most hormones and metabolites to return to prepartum concentrations. Diurnal variations in response to feeding twice daily were most evident for growth hormone, free fatty acids, and total amino acids. The 3-wk postpartum and ketonemic periods gave the greatest responses to feeding. Molar ratios of insulin to glucagon and insulin to growth hormone tended to decrease at 3 wk postpartum and decreased further in ketonemia, demonstrating hormonal adaptations to decreased energy intake during lactation. Lactation ketosis results from more than severe energy deficit.
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PMID:Glucagon, insulin, growth hormone, and some blood metabolites during energy restriction ketonemia of lactating cows. 388 31

Azathioprine (2 mg/kg) was given, in addition to routine insulin treatment, to alternate patients presenting with recent-onset type I diabetes. Treated (N = 13) and untreated (N = 11) patients did not differ significantly at diagnosis with respect to age, duration of symptoms, body weight, blood glucose, hemoglobin A1c, or presence of ketosis. Eight patients were treated for 12 mo, three elected to stop treatment at 6 mo, and treatment was stopped in two because of side effects. Seven treated patients had a remission compared with one untreated patient. At 12 mo these seven patients were distinguished by significantly higher basal and glucagon-stimulated levels of C-peptide (1.98 +/- 0.52 and 3.88 +/- 0.34 micrograms/L, respectively) compared with the other six treated patients (0.93 +/- 0.52 and 1.32 +/- 0.85 microgram/L, respectively), and by the persistence of islet cell cytoplasmic antibodies. Remissions were not sustained in the 1-2 yr after treatment, although relapsed patients required less insulin for control. These results corroborate those from nonrandomized trials using cyclosporine and suggest that protracted treatment with nonspecific immunosuppressive drugs may be necessary to avert insulin dependence.
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PMID:Increase in remission rate in newly diagnosed type I diabetic subjects treated with azathioprine. 390 63

In an attempt to explain the rarity of ketonuria in Indian diabetics, plasma glucose, insulin and free fatty acid (FFA) levels were measured in 35 non-obese patients with non-insulin-dependent diabetes in the young and 35 matched controls during a 100 g oral glucose tolerance test. Compared with the controls, the patients had a severe degree of hyperglycaemia, fasting hyperinsulinism, and an attenuated and delayed insulinaemic response. However, in addition to the fasting plasma FFA levels being similar in the two groups, the decrement in the FFA responses was equivalent. Thus, the hormone-sensitive lipase of the adipose tissue appeared to be sensitive to inhibition by insulin. Also, the fasting insulin:glucagon molar ratios were computed and found to be no different in the two groups. The normal fasting FFA levels, relative sensitivity to insulin of lipolysis in the adipocyte and normal insulin: glucagon molar ratios may help to explain in part the general rarity of ketosis-prone diabetes in the South African Indian population.
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PMID:A plausible explanation for the aketonuria of young Indian non-insulin-dependent diabetics. 392 67

Adaptation to fasting results in ketosis, protein conservation, and diminished energy requirements. To determine whether the attenuation of these responses following injury is due to an altered hormonal environment, we infused the catabolic hormones cortisol, glucagon, and adrenaline into seven fasting subjects for 72 h. Saline alone was administered during a comparable control period. Hormone infusion achieved blood levels typical of moderate injury and resulted in hypermetabolism, hyperglycaemia, hyperinsulinaemia, and marked suppression of fasting ketosis. The hypoketonaemia could not be accounted for by decreased precursor availability, accelerated ketone utilization or increased urinary excretion. The altered hormonal environment associated with critical illness attenuates fasting ketosis by limiting hepatic ketogenesis.
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PMID:Role of catabolic hormones in the hypoketonaemia of injury. 394 99

Plasma free carnitine and acylcarnitines were determined in man during acutely induced insulin deficiency. A 5-hr infusion of somatostatin at 6 microgram/min in 10 thin subjects produced profound, sustained hypoinsulinemia and led to rapid increases in plasma free fatty acids and ketoacids (peak increments of 0.67 mM each). Simultaneously, plasma free carnitine decreased, while plasma long-chain and short-chain acylcarnitines increased significantly. When hyperglucagonemia was created by inclusion of glucagon with the somatostatin, the hyperketonemia was reversed after 2 hr and the increase in acylcarnitine abolished. However, the decrease in free carnitine was accentuated. The antiketogenic effect of adding glucagon was due to an eventual breakthrough of the somatostatin blockade on insulin secretion, the latter gradually returning toward preinfusion levels. Inclusion of exogenous insulin with the somatostatin-glucagon infusion immediately lowered free fatty acids and ketoacids. Acylcarnitines also declined promptly, while the accelerated fall in free carnitine produced by glucagon was blunted by the addition of insulin. Qualitatively and quantitatively comparable results were seen in seven obese subjects. This study suggests: (1) the increase in plasma acylcarnitines previously described in fasting and diabetic ketosis is largely due to insulin deficiency; (2) the corresponding decrease in plasma free carnitine is attributable both to insulin deficiency and glucagon excess; and (3) the resistance of obese subjects to ketosis is unlikely to be due to deficits in carnitine or carnitine acyltransferases.
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PMID:Acute hormonal effects on carnitine metabolism in thin and obese subjects: responses to somatostatin, glucagon, and insulin. 611 Oct 18

The metabolic effects of chronic hypercortisolaemia were studied by administration of tetracosactrin-depot, 1 mg I.M. daily for 36-60 hr to normal subjects. Partial insulin and glucagon deficiency were induced at the end of the period by infusion of somatostatin, 100 micrograms/h for 210 min. Tetracosactrin alone induced a three fold rise in basal serum cortisol levels and fasting blood glucose concentration rose from 5.2 +/- 0.2 to 7.2 +/- 0.2 mmole/l (p less than 0.01) with a rise in fasting serum insulin from 5.2 +/- 1.2 to 13.1 +/- 1.9 mU/l (p less than 0.02). Concentrations of the gluconeogenic precursors lactate, pyruvate and alanine were also raised, but non-esterified fatty acid, glycerol and ketone body levels were unchanged. Somatostatin infusion caused a 30%-50% decrease in serum insulin and a 20%-60% decrease in plasma glucagon concentrations both before and after tetracosactrin administration. A similar rise in blood glucose concentration, relative to the saline control, occurred over the period of somatostatin infusion both with and without elevated cortisol levels. However, prior tetracosactrin administration caused a 100% greater rise in blood ketone body concentrations during infusion of somatostatin than was seen in the euadrenal state, despite similar plasma NEFA concentrations. Hypercortisolaemia causes hyperglycaemia and elevated gluconeogenic precursor concentrations but the associated rise in serum insulin concentrations limits lipolysis and ketosis. In insulin deficiency, a ketotic effort of glucocorticoid excess is evident which may be independent of lipolysis and occurs despite concurrent glucagon deficiency. These catabolic actions of cortisol are likely to be of major importance in the metabolic response to stress.
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PMID:Metabolic effects of cortisol in man--studies with somatostatin. 612 62

In normal and diabetic pregnancies, the placenta functions as a complex endocrine gland that modulates all classes of maternal nutrients to the fetus. The metabolic alterations of normal pregnancy are diabetogenic and associated with modest resistance to endogenous insulin. Pregnant women with carbohydrate intolerance represent three metabolically heterogeneous groups: type I (insulin-dependent), type II (non-insulin-dependent), and gestational diabetes. Patients with type I diabetes are at risk for ketosis and require replacement therapy because of a deficient production of insulin. They have decreased 24-hour, around-the-clock levels of C-peptide and glucagon, and lower nocturnal cortisol values and higher 24-hour prolactin levels than those of women with type II diabetes. Type II pregnant diabetic patients are not prone to ketosis and are more resistant to endogenous and exogenous insulin. They have higher fasting and meal-stimulated levels of C-peptide, accentuated fasting hypertriglyceridemia, and significantly lower high-density lipoprotein cholesterol levels than those of normal or type I women. In gestational diabetes, the metabolic stress of pregnancy evokes reversible hyperglycemia which may be associated with either a surfeit or a deficiency of insulin. These metabolic differences among diabetic pregnant women could have implications for placental structure and function that might influence fetal growth.
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PMID:Alterations of maternal metabolism in normal and diabetic pregnancies: differences in insulin-dependent, non-insulin-dependent, and gestational diabetes. 634 40


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