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)

We investigated the effects on glucose metabolism of the infusion of either long-chain triglycerides (LCT), a mixture of long-chain and medium-chain triglycerides (MCT/LCT), D-beta-hydroxybutyrate (D-beta-OHB), or saline in normal postabsorptive subjects. Plasma insulin, C-peptide, and glucagon concentrations were unchanged in all groups. LCT and MCT/LCT infusions increased levels of plasma free fatty acids (FFA) compared with those of the saline group, whereas D-beta-OHB decreased them. Plasma ketone body concentrations were higher during the D-beta-OHB and triglyceride infusions than during the saline test. Glucose concentrations and appearance (Ra) and disappearance (Rd) rates were not modified during saline infusion. Glucose levels decreased only in the D-beta-OHB and MCT/LCT groups (P < .05), whereas they were unchanged during LCT infusion. Glucose Ra decreased slightly by 15% to 17% in LCT, MCT/LCT, and D-beta-OHB groups (P < .05 v saline). Glucose Rd decreased by 14% to 16% in each lipid-infusion group (P < .05 v saline). Glucose clearance rates decreased by 14% only in the LCT group (P < .001). Glucose oxidation rates did not change significantly during the lipid substrate infusions compared with saline infusion. In conclusion, (1) the effects of fatty acids on glucose metabolism appear to depend on the fatty acid chain length, since only LCT infusion significantly impaired glucose utilization; and (2) in subjects with normal endocrine pancreas function, we found no adverse effects of a short-term increase in lipid substrate availability on glucose production rate and concentration.
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PMID:Effects of different lipid substrates on glucose metabolism in normal postabsorptive humans. 146 Nov 33

Major trauma provokes a stress response which is mediated, in part, via glucagon, catecholamines, and cortisol. These stress hormones modulate the choice of energy substrate for various tissues. While glucose and fatty acids are considered the preferred fuels, ketone bodies (26/ATP/mole) may be a viable alternative. In this study, we measured the concentrations of acetoacetate and beta-hydroxybutyrate (3-OHB) in the portal as well as systemic circulations of 10 critically injured patients (revised trauma score = 6.8 +/- 0.5, injury severity score = 27 +/- 3) during the first 5 postoperative days. At 6 hr postinjury, 3-OHB was elevated in the portal system (0.34 +/- 0.01 mM) while depressed systemically (0.09 +/- 0.02 mM), indicating that the gut was capable of ketogenesis. In contrast, at 24 hr, 3-OHB rose systemically (0.39 +/- 0.02 mM) while decreasing in portal blood (0.09 +/- 0.01 mM) implying gut ketone consumption. Moreover, the systemic ketone body ratio became elevated at 24 hr, suggesting an enhanced liver energy status. In summary, we believe ketogenesis is stimulated by major trauma. Initially, the gut supports ketone concentration in the systemic circulation, whereas, by 24 hr, the gut becomes a ketone consumer and the liver maintains circulating levels.
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PMID:Gut and liver coordinated metabolic response following major torso injury. 154 64

Whereas the lipolytic and diabetogenic consequences of sustained growth hormone (GH) exposure are well described, the metabolic effects of a short-lived physiological GH pulse have only recently been reported. To assess the possible dose-response of such short-term bolus administration of GH, six healthy, male subjects were each studied thrice for 4 1/2 hours after an intravenous (IV) bolus of either 70, 140, or 350 micrograms GH, resulting in peak GH concentrations of 10, 15, and 34 micrograms/L. Observed results include: (1) Time- (but not dose-) dependent changes (P less than .05) in plasma glucose and an acute (from 10 minutes onward), persistent, 40% decrease in forearm glucose uptake. Total glucose turnover decreased steadily with time on all occasions. (2) Time- and dose-dependent increases (P less than .05) in the concentrations of circulating lipid intermediates, with an increase of 3-hydroxybutyrate (3-OHB) from a basal of 35 mumol/L to peak values of 108 +/- 34 (70 micrograms), 176 +/- 46 (140 micrograms), and 232 +/- 51 mumol/L (350 micrograms), forearm uptake of 3-OHB changed in parallel. (3) Respiratory exchange ratio decreased (P less than .05) with increasing GH doses (indicating increased lipid and decreased glucose oxidation), and energy expenditure remained unaffected. (4) Concentrations of insulin, C-peptide, and glucagon were unchanged throughout all studies. We conclude that the stimulating effects of a modest GH bolus on circulating lipid intermediates and lipid oxidation are dose-dependent. This finding underlines the potential role of GH as a principal physiological regulator of fuel consumption in the maintenance of metabolic homeostasis.
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PMID:Dose-response studies on the metabolic effects of a growth hormone pulse in humans. 173 39

To assess the metabolic effects of moderate hyperketonemia, six young male type 1 diabetic patients received a 200-minute intravenous (IV) infusion of (1) 0.9 mmol 3-hydroxybutyrate (3-OHB)/kg/h, and (2) saline. To ensure comparable metabolic conditions, a low-dose hyperinsulinemic euglycemic glucose clamp was performed from 5 hours before and throughout 3-OHB/saline infusions. The forearm technique was employed to estimate substrate fluxes in muscle. Infusion of 3-OHB caused: (1) increases (P less than .05) in circulating levels of 3-OHB (from 112 +/- 73 mumol/L to 825 +/- 111 mumol/L) and forearm arteriovenous differences of 3-OHB (from 19 +/- 10 mumol/L to 145 +/- 46 mumol/L), as well as an eightfold increase of plasma acetoacetate. (2) Decreased (P less than .05) levels of nonesterified fatty acids (NEFA; from 466 +/- 85 mumol/L to 201 +/- 14 mumol/L) and glycerol (from 39 +/- 7 mumol/L to 11 +/- 4 mumol/L) and decreased (P less than .05) arteriovenous differences of glycerol (from -16 +/- 8 mumol/L to -3 +/- 2 mumol/L). (3) Increased (P less than .05) levels of serum growth hormone (GH; from 4.1 +/- 1.5 micrograms/L to 15.9 +/- 8.0 micrograms/L). No change was recorded in circulating concentrations of free insulin, glucagon, glucose, lactate, or alanine. Nor were arteriovenous balances of these intermediary metabolites, isotopically determined glucose turnover or amounts of exogenously administered glucose affected. In conclusion, in type 1 diabetic man, the main regulatory effect of isolated hyperketonemia appears to be a direct negative feedback inhibition of lipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substrate metabolism during modest hyperinsulinemia in response to isolated hyperketonemia in insulin-dependent diabetic subjects. 224 73

The effects of 3-hydroxybutyrate (3-OHB) and hyperosmolarity on glucagon secretion were examined in the isolated perfused canine pancreas. When 3-OHB was infused for 15 min into the pancreas perfused with 2.8 mM glucose, 5 and 20 mM sodium 3-OHB inhibited it after a transient stimulation, whereas a similar transient stimulation was observed also by the infusion of 20 mM NaCl in a control experiment. The above inhibition was not observed under the perfusate condition of 5.5 mM glucose plus 10 mM arginine. When the isolated canine pancreas was perfused under the perfusate condition of acidosis (pH 7.1), ketoacidosis (pH 7.1 and 20 mM 3-OHB) or hyperosmolarity (+60 mOsm/kg with sucrose) throughout the experiment, the glucagon concentrations produced by 2.8 mM glucose under the ketoacidotic and hyperosmolar conditions, were less than half of those obtained under the standard condition. The insulin level was not influenced by the above perfusate conditions. These results suggest that 3-OHB inhibits glucagon secretion stimulated by glucopenia, but does not inhibit it stimulated by amino acids, and that hyperosmolarity inhibits glucagon secretion but does not inhibit insulin secretion. The pathophysiological significance of these results must be slight, considering the presence of hyperglucagonemia during prolonged starvation or diabetic ketoacidosis.
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PMID:Effects of 3-hydroxybutyrate and hyperosmolarity on glucagon release from isolated perfused canine pancreas. 268 20

Several in vivo studies have indirectly suggested a relationship between blood glutamine and ketonemia. The present study was designed to characterize the role glutamine plays in regulating lipolysis and ketogenesis during fasting in vivo. Twelve dogs had catheters implanted in the hepatic and portal veins (V) and in the femoral artery (A) 17-21 days before study. The animals were fasted for 4 days. After a 120-min rest and 40-min basal periods, 6 dogs received an infusion of L-glutamine at 6 mumol X kg-1 X min-1 and 6 received saline and acted as controls. Hepatic and splanchnic balances (mumol X kg-1 X min-1) were estimated by A-V differences multiplied by blood flow determined by indocyanine green. Fasting was associated with a compensated (no change in pH) mild metabolic acidosis but no change in plasma insulin and glucagon or blood glutamine. L-Glutamine infusion increased blood glutamine by 20% but decreased arterial free fatty acids (FFA, from 1,054 +/- 47 to 850 +/- 43 mumol/l, P less than 0.01), beta-hydroxybutyrate (beta-OHB, from 136 +/- 15 to 66 +/- 8 mumol/l, P less than 0.01), acetoacetate (AcAc, from 168 +/- 26 to 86 +/- 21 mumol/l, P less than 0.01), and glycerol (from 90 +/- 4 to 65 +/- 5 mumol/l, P less than 0.01). It also decreased hepatic uptake of glycerol (from 2.5 +/- 0.5 to 0.8 +/- 0.3 mumol X kg-1 X min-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine blocks lipolysis and ketogenesis of fasting. 351 12

Hyperinsulinism frequently accompanies glucose normalization in type I diabetes but the long-term consequences of this exaggerated hormonal state are not known. To study this condition, normal dogs received constant exogenous sulfated insulin infusions for prolonged periods up to 43 weeks. During the interval and inspite of prevailing postabsorptive and fasting hypoglycemia, overt resistance to the infused insulin or loss of sensitivity did not occur. In counterring the imposed fasting hyperinsulinemia and the resulting hypoglycemia, fasting pancreatic glucagon levels rose while the fasting levels of several glucogenic precursors (lactate, pyruvate, and alanine) decreased. Fasting free fatty acid (FFA) levels were suppressed, but beta-hydroxybutyrate (beta-OHB) levels were unchanged. Body weight did not change. Most remarkably, all changes measured in the fasting levels of the hormones and metabolites reverted to normal following the cessation of exogenous sulfated insulin infusion. In addition to the hormonal and metabolite adaptations invoked by chronic exogenous hyperinsulinism in the fasting state of these normal dogs, there were interesting responses to their usual mixed meals. Of particular interest in this regard were the plasma glucose, insulin, and FFA diurnal profiles. First of all, a definite and unusual postprandial glycemic excursion occurred. Second, insulin levels were elevated some sixfold, and rather unresponsive to the meal in general. Inspite of the depressed fasting FFA levels and the absence of a postprandial rise in insulinemia, FFA showed a distinct fall after the meal. Whether the sulfated insulins infused were of the bovine or porcine species of origin made no discernible difference.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The metabolic and hormonal adaptations of normal dogs to long-term exogenous sulfated insulin infusions. 353 58

The relative tissue specificities of biosynthetic human proinsulin and porcine insulin were compared in eight insulin-deficient diabetic patients. Variable proinsulin and insulin infusions were administered iv for at least 18 h on separate occasions to achieve euglycemia. Once equivalence with respect to this end point was established, the paired infusions were made constant and compared with respect to their effect on plasma glucose, hepatic glucose output (Ra), glucose utilization, glucose clearance, and blood beta-hydroxybutyrate, alanine, and glycerol in response to a glucagon infusion (3 ng/kg X min). Basal Ra did not differ between euglycemia established using proinsulin vs. insulin [1.92 +/- 0.12 vs. 1.65 +/- 0.07 mg/kg X min] when data were analyzed by multivariate analysis of variance; likewise, the increment in Ra in response to glucagon infusion did not differ between the two treatments (1.26 +/- 0.22 vs. 1.17 +/- 0.24 mg/kg X min). Blood beta OHB, alanine, and glycerol also did not differ between the insulin and proinsulin treatments. Under these conditions of prolonged infusion in which the differences in clearance properties between proinsulin and insulin do not play a role and which maintain basal euglycemia, the two compounds equally limit the response to a stimulus to hepatic glucose production. Under nonsteady state conditions, when the differences in clearance rates are operative, proinsulin may have relatively greater effects on Ra than do doses of insulin that are biologically equivalent after prolonged infusions.
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PMID:The effect of biosynthetic human proinsulin on the hepatic response to glucagon in insulin-deficient diabetes. 354 47

Using a non-recirculating perfusion system, we studied the time course of ketone body output from the isolated rat liver in response to various hormones and changes in pH and redox state. The release of 3-hydroxybutyrate (3-OHB) started to be suppressed within 1 min after the addition of insulin (50 mU/ml) and kept half of the basal level even 10 min after its cessation. The addition of glucagon (0.2 microM) caused an increase in both 3-OHB and acetoacetate (AcAc) outputs from fed livers within 5 min, which reached about 150% of the basal level 10 min after the infusion and maintained a constant level through out the experiment. Growth hormone (2 mu/ml) elicited a slight but significant increase in AcAc output soon after the infusion. Epinephrine (10 microM) also caused a slight increase in both AcAc and 3-OHB outputs 9 min after the infusion and maintained a significant increase even 10 min after stopping infusion. The decrease in pH of the perfusate or the addition of ascorbic acid abruptly suppressed the AcAc production. In summary, the present study clearly demonstrated the direct effects of various hormones on ketogenesis in the liver and the usefulness of a non-recirculating liver perfusion system as a tool for the study of ketogenesis.
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PMID:Time course of ketone body production in the isolated perfused rat liver in response to various stimuli. 355 47

The influence of ketone body infusion on the serum GH and glucagon response to FFA depression and insulin hypoglycemia was investigated in 10 healthy men. Intravenous infusion of nicotinic acid induced suppression of both FFA and ketone bodies. This was accompanied by a delayed GH increase to 21.1 +/- 6.9 ng/ml (at 300 min). During an additional beta-hydroxybutyrate (OHB) infusion, FFA remained depressed, but ketone bodies were elevated, and the GH response was abolished (maximum 5.6 +/- 1.6 ng/ml). During infusion of OHB alone, FFA were suppressed. GH increased significantly, although less markedly than during suppression of both FFA and ketone bodies (to 9.3 +/- 3.1 ng/ml at 270 min). No GH rise occurred when both FFA and ketone bodies were kept elevated by the addition of a lipid infusion. The GH rise in response to insulin hypoglycemia was not changed by an OHB infusion (43.2 +/- 4.6 vs. 48.0 +/- 7.3 ng/ml). However, OHB increased the net GH output by significantly delaying the return to basal concentrations in the presence of a reduced FFA rebound. An effect of OHB infusion on the plasma glucagon concentration during all experiments was small, and its physiological significance is doubtful. These results confirm that FFA depression induces delayed GH secretion. They suggest that this is not wholly dependent on concomitant depression of ketone bodies. On the other hand, when ketone bodies are elevated, the GH response to FFA depression is diminished or absent. The net GH response to changes in lipid substrates probably depends on the concentration of both FFA and ketone bodies.
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PMID:Influence of ketone body infusion on plasma growth hormone and glucagon in man. 634 66


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