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)

Double isotope procedures (3H and 14C) were used in vivo to investigate a) slow long-term gluconeogenic actions of adrenal glucocorticoids, and b) rapid stimulation of gluconeogenesis by glucagon. [U-14C,6-3H]Glucose was administered to normal and adrenalectomized rats. No effect was observed on the [6-3H]glucose half-life suggesting the dicarboxylic acid shuttle is unaffected by adrenalectomy; the Cori cycle is also not influenced. Loads of [14C]aspartate, [14C]glutamate, or [14C]alanine were given to normal and adrenalectomized rats. Simultaneously, in vivo transaminase activity was studied by measuring the appearance of 3H2O in body water after administration of [2-3H]aspartate, [2-3H]glutamate, or [2-3H]alanine, Adrenalectomy has no influence on the incorporation of glutamate or aspartate into glucose or on their in vivo transaminases. Diminution of incorporation of [14C]alanine into glucose and alanine transaminase activities occurs only when rats are given unphysiological loads. These studies support the contention that glucocorticoid rate-limiting actions occur in extrahepatic tissues to produce an increased flow of glucose precursors to the liver. [U-14C,3-3H]Glucose was used to investigate the effect of glucagon on the hepatic fructose-6-phosphate (F-6-P) cycle. Glucagon administration resulted in a rapid drop in the 3H/14C ratio of circulating glucose, suggesting an increase in F-6-P recycling caused by activation of FDPase with little or no decrease in phosphofructokinase. Such a change would direct substrate flux toward gluconeogenesis.
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PMID:Use of 3H and 14C doubly labeled glucose and amino acids in the study of hormonal regulation of gluconeogenesis in rats. 19 46

Quinolinic acid (Q.A.) which inhibits gluconeogenesis at the site of phosphoenolpyruvate (PEP) synthesis, reduced the content of PEP while elevating that of aspartate and malate in rat livers perfused with a medium containing 10 mM L-lactate. Glucagon at 10(-9) M did not affect Q.A. inhibition of lactate gluconeogenesis nor the depression of PEP level, but further elevated malate and aspartate accumulation. Exogenous butyrate had the same effect as glucagon on these parameters. Butylmalonate (BM), an inhibitor of mitochondrial malate transport, inhibited lactate and propionate gluconeogenesis to similar extents. The addition of 10(-9) M glucagon had no effect on BM inhibition of lactate gluconeogenesis, but almost completely reversed BM inhibition of propionate gluconeogenesis. These results suggest that glucagon may act on at least two sites, resulting in elevated hepatic gluconeogenesis. First, it may stimulate dicarboxylic acid synthesis (malate and oxaloacetate, specifically) through activation of pyruvate carboxylation. Secondly, it may stimulate synthesis of other dicarboxylic acids (fumarate, for example) by activating certain steps of the tricarboxylic acid cycle. The stimulatory effect of glucagon on gluconeogenesis in the perfused rat liver is well documented (1, 2). Exton et al., who earlier located the site of stimulation between pyruvate and PEP synthesis (3), proposed that glucagon stimulated PEP synthesis in the perfused rat liver (4), while reports from Williamson et al. (5) suggested the pyruvate-carboxylase reaction as the site of glucagon action. Stimulation at sites above PEP formation and of portions of the tricarboxylic acid cycle (4) by glucagon have also been suggested (6). In the present experiments, we have used substrates entering at different parts of the gluconeogenic pathway, and specific inhibitors to further resolve the action of glucagon.
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PMID:Effects of glucagon on gluconeogenesis from lactate and propionate in the perfused rat liver. 125 Aug 74

Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects.
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PMID:Metabolic effects and disposition of sebacate, an alternate dicarboxylic fuel substrate. 159 Jun 67

Propionate and pyruvate added to isolated normal and biotin-deficient adult rat hepatocytes increase the production of glucose. This production decreases about 30% on biotin deficiency. Malonate inhibits gluconeogenesis from propionate showing the metabolic transformation of propionyl-CoA via the Krebs cycle. Neither glucagon nor dibutyryl-cyclic AMP significantly stimulate gluconeogenesis.
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PMID:Some biochemical observations on gluconeogenesis from propionate in hepatocytes isolated from normal and biotin-deficients rats. 298 49

The purpose of the present study was to determine whether central administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a selective metabotropic glutamate receptor agonist, would stimulate glucose metabolism, activate the hypothalamic-pituitary-adrenal axis, or influence pancreatic endocrine secretion. Intracerebroventricular injection of ACPD increased arterial glucose levels by 60% within 15 min, which were sustained throughout the 3-h experimental protocol. This hyperglycemia resulted from an early increase in hepatic glucose production (HGP, 88%) that exceeded the increase in glucose uptake by peripheral tissues (66%). Stimulation of glucose metabolism was associated with transient elevations in plasma insulin (145%) and glucagon (3-fold) levels and more sustained elevations in corticosterone (141%), epinephrine (3- to 5-fold), and norepinephrine (32-110%). Intravenous infusion of alpha- and beta-adrenergic antagonists prevented the ACPD-induced increase in glucose metabolism. Arterial blood pressure, cardiac index, and total peripheral resistance were not altered after ACPD. Overall, the changes in regional blood flow were unremarkable, although ACPD did increase blood flow to the liver (2-fold) and heart (48%) and decrease flow to the stomach (33%). These results indicate that central administration of ACPD 1) enhances HGP, which is primarily mediated by adrenergic stimulation; 2) increases glucose uptake by peripheral tissues, which appears to be mediated by both hyperinsulinemia and hyperglycemia; 3) stimulates pancreatic and adrenal hormone secretion independent of adrenergic activation; and 4) produces minimal changes in regional blood flow that cannot explain the glucose metabolic response produced by ACPD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic, hormonal, and hemodynamic changes induced by metabotropic excitatory amino acid agonist (1S,3R)-ACPD. 773 85

Dicarboxylic acids have been proposed as an alternate lipid energetic substrate for total parenteral nutrition. No data are yet available on the possible effect of dicarboxylic acids on glucose metabolism in humans. Thus, we examined the effect of a continuous intravenous infusion of the sodium salt of the 10-carbon atom alyphatic dicarboxylic acid, sebacate (Sb), on insulin-dependent glucose metabolism in four control subjects, four patients with insulin-dependent diabetes mellitus, and four obese subjects. All subjects received a constant 5-hour infusion of saline or sebacate (6.6 g/h), in a randomized order on two different days. After 3 hours of infusion, a 120-minute euglycemic, hyperinsulinemic clamp procedure was performed (insulin infusion rate = 40 mU/m2 per minute). Glucose uptake, plasma sebacate, insulin, glucagon, C-peptide, and ketone bodies were measured. No significant differences in insulinemia were found among groups either during the saline infusion or the sebacate infusion. On the contrary, glucose uptake (molar) was significantly reduced during the sebacate vs the saline day in all three groups: 6.7 +/- 0.04 vs 3.7 +/- 1.3 in control subjects (p < .001), 4.6 +/- 0.4 vs 2.5 +/- 1.2 in patients with insulin-dependent diabetes mellitus (p < .001), and 4.8 +/- 0.5 vs 2.7 +/- 0.2 mg/kg per minute in obese subjects (p < .001). In conclusion, Sb administration was associated with a glucose-sparing effect as shown by the reduced glucose uptake in all patients studied. Sebacate did not stimulate insulin secretion, inasmuch as no modification of C-peptide plasma levels was observed after 3 hours of Sb infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dicarboxylic acids and glucose utilization in humans: effect of sebacate. 816 96