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 various carbohydrates on glucagon-like peptide-1 (GLP-1) release was studied in the in vivo perfused rat ileum. GLP-1 concentrations in the mesenteric venous effluent increased significantly after luminal perfusion with substrates of a sodium/glucose co-transporter (D-glucose, D-galactose, methyl-alpha D-glucoside, and 3-O-methyl-D-glucose). D-Fructose induced a sodium-independent release of GLP-1. Carbohydrates like 2-deoxy-D-glucose and N-acetyl-D-glucosamine, which are not substrates of a luminal sodium/glucose or fructose transporter, did not affect GLP-1 release. Since methyl-alpha D-glucoside is not a substrate of the basolateral glucose transport mechanism and 3-O-methyl-D-glucose is not metabolized within intestinal cells, it is concluded that intracellular metabolism of carbohydrates and intracellular removal are not essential to induce GLP-1 secretion in rats.
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PMID:Release of glucagon-like peptide-1 (GLP-1) by carbohydrates in the perfused rat ileum. 913 52

Fructose activates glucokinase by releasing the enzyme from its inhibitory protein in liver. To examine the importance of acute activation of glucokinase in regulating hepatic glucose uptake, the effect of intraportal infusion of a small amount of fructose on net hepatic glucose uptake (NHGU) was examined in 42 h-fasted conscious dogs. Isotopic ([3-3H] and [U-14C]glucose) and arteriovenous difference methods were used. Each study consisted of an equilibration period (-90 to -30 min), a control period (-30 to 0 min), and a hyperglycemic/hyperinsulinemic period (0-390 min). During the latter period, somatostatin (489 pmol x kg(-1) x min(-1)) was given, along with intraportal insulin (7.2 pmol x kg(-1) x min(-1)) and glucagon (0.5 ng x kg(-1) x min(-1)). In this way, the liver sinusoidal insulin level was fixed at four times basal (456 +/- 60 pmol/l), and liver sinusoidal glucagon level was kept basal (46 +/- 6 ng/l). Glucose was infused through a peripheral vein to create hyperglycemia (12.5 mmol/l plasma). Hyperglycemic hyperinsulinemia (no fructose) switched net hepatic glucose balance (micromoles per kilogram per minute) from output (11.3 +/- 1.4) to uptake (14.7 +/- 1.7) and net lactate balance (micromoles per kilogram per minute) from uptake (6.5 +/- 2.1) to output (4.4 +/- 1.5). Fructose was infused intraportally at a rate of 1.7, 3.3, or 6.7 micromol x kg(-1) x min(-1), starting at 120, 210, or 300 min, respectively. In the three periods, portal blood fructose increased from <6 to 113 +/- 14, 209 +/- 29, and 426 +/- 62 micromol/l, and net hepatic fructose uptake increased from 0.03 +/- 0.01 to 1.3 +/- 0.4, 2.3 +/- 0.7, and 5.1 +/- 0.6 micromol x kg(-1) x min(-1), respectively. NHGU increased to 41 +/- 3, 54 +/- 5, and 69 +/- 8 micromol x kg(-1) x min(-1), respectively, and net hepatic lactate output increased to 11.0 +/- 3.2, 15.3 +/- 2.7, and 22.4 +/- 2.8 micromol x kg(-1) x min(-1) in the three fructose periods, respectively. The amount of [3H]glucose incorporated into glycogen was equivalent to 69 +/- 3% of [3H]glucose taken up by the liver. These data suggest that glucokinase translocation within the hepatocyte is a major determinant of hepatic glucose uptake by the dog in vivo.
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PMID:Small amounts of fructose markedly augment net hepatic glucose uptake in the conscious dog. 960 61

The purpose of the present study was to evaluate the effects of an intraperitoneal injection of sodium phosphate on the metabolic and hormonal responses to exercise. Fructose-injected rats were either injected with sodium phosphate (Na2HPO4) or NaCl, either in a fed or in a food-restricted state (24 h), and evaluated at rest or after a 30-min exercise period (26 m/min; 0% grade). Liver ATP, phosphate (Pi), and glycogen concentrations were, on the whole, significantly (p < 0.05) higher in Na2HPO4 than in NaCl groups. Exercise resulted in a significant (p < 0.01) decrease in liver ATP and glycogen levels in fed and food-restricted rats whether injected with NaCl or Na2HPO4. Exercise, after NaCl and Na2HPO4 injection, resulted in a significant (p < 0.01) increase in liver phosphate and Pi/ATP ratio, and in a decrease in glucose and an increase in glucagon levels in food-restricted rats only. The normal exercise-induced increase in plasma FFA, glycerol, and norepinephrine levels (p < 0.05), observed in both fed and food-restricted NaCl-injected rats, was abolished by the injection of phosphate. The data are in line with the new concept that in addition to blood glucose levels, the increase in liver Pi/ATP ratio could also contribute to the increase in glucagon response during exercise.
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PMID:Effects of phosphate injection on metabolic and hormonal responses to exercise in fructose-injected rats. 1060 47

D-Fructose has been found to increase uric acid production by accelerating the degradation of purine nucleotides, probably due to hepatocellular depletion of inorganic phosphate (Pi) by an accumulation of ketohexose-1-phosphate. The hyperuricemic effect of D-tagatose, a stereoisomer of D-fructose, may be greater than that of D-fructose, as the subsequent degradation of D-tagatose-1-phosphate is slower than the degradation of D-fructose-1-phosphate. We tested the effect of 30 g oral D-tagatose versus D-fructose on plasma uric acid and other metabolic parameters in 8 male subjects by a double-blind crossover design. Both the peak concentration and 4-hour area under the curve (AUC) of serum uric acid were significantly higher after D-tagatose compared with either 30 g D-fructose or plain water. The decline in serum Pi concentration was greater at 50 minutes after D-tagatose versus D-fructose. The thermogenic and lactacidemic responses to D-tagatose were blunted compared with D-fructose. D-Tagatose attenuated the glycemic and insulinemic responses to a meal that was consumed 255 minutes after its administration. Moreover, both fructose and D-tagatose increased plasma concentrations of cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1). The metabolic effects of D-tagatose occurred despite its putative poor absorption.
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PMID:D-tagatose, a stereoisomer of D-fructose, increases blood uric acid concentration. 1095 12

In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load. Therefore, we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers (5 men and 6 women). Each subject underwent an oral glucose tolerance test (OGTT) on 2 separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without 7.5 g fructose (OGTT+F or OGTT-F), in random order. Arterialized blood samples were obtained from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward. The area under the curve (AUC) of the change in plasma glucose was 19% less in OGTT+F vs. OGTT-F (P: < 0.05). Glucose tolerance was improved by fructose in 9 subjects and worsened in 2. All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F (31 +/- 5% decrease). The insulin AUC did not differ between the 2 studies. Of the 9 subjects with improved glucose tolerance during the OGTT+F, 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50% greater during the OGTT+F (P: < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTT. In conclusion, low dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.
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PMID:Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults. 1113 1

Fructose-2,6-bisphosphate is responsible for mediating glucagon-stimulated gluconeogenesis in the liver. This discovery has led to the realization that this compound plays a significant role in directing carbohydrate fluxes in all eukaryotes. Biophysical studies of the enzyme that both synthesizes and degrades this biofactor have yielded insight into its molecular enzymology. Moreover, the metabolic role of fructose-2,6-bisphosphate has great potential in the treatment of diabetes.
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PMID:PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate. 1116 14

Glucokinase (GK) is required for cellular glucose sensing, although there is a paucity of data regarding its role in the counterregulatory response to hypoglycemia in humans. Because fructose has been shown to modulate GK activity, we examined the effects of an acute infusion of fructose on hypoglycemia counterregulation in seven lean nondiabetic subjects. Using stepped hypoglycemia clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/l target plasma glucose steps, 50 min each), subjects were studied on two separate occasions, without (control) or with co-infusion of fructose (1.2 mg.kg(-1).min(-1)). Fructose induced a resetting of the glycemic thresholds for secretion of epinephrine (3.8 +/- 0.1 mmol/l) and glucagon (3.9 +/- 0.2 mmol/l) to higher plasma glucose concentrations (4.0 +/- 0.1 mmol/l [P = 0.006] and 4.1 +/- 0.1 mmol/l [P = 0.03], respectively). In addition, the magnitude of increase in epinephrine and glucagon concentrations was higher after administration of fructose (48 and 39%, respectively, P < 0.05 for both). The amplification of these hormonal responses was specific because plasma norepinephrine, growth hormone, and cortisol were comparable in both sets of studies. Endogenous glucose production, measured with [3-(3)H]glucose, increased by 47% (P < 0.05) in the fructose infusion studies compared with 14% (P = NS) in the control studies. In addition, glucose uptake was more suppressed with fructose infusion (by 33%, P < 0.05). In concert with these effects of fructose on glucose kinetics, average glucose infusion rate was markedly reduced in the fructose infusion studies during the 3.9-mmol/l glucose step (4.6 +/- 0.9 vs. 7.4 +/- 1.1 micromol.kg(-1).min(-1), respectively, P = 0.03) and during the 3.3-mmol/l glucose step (0.5 +/- 0.1 vs. 5.2 +/- 1.2 micromol.kg(-1).min(-1), respectively, P < 0.001), suggesting more potent glucose counterregulation and improved recovery from hypoglycemia with fructose infusion. We conclude that infusion of a catalytic dose of fructose amplifies the counterregulatory response to hypoglycemia by both increases in hormonal activation and augmentation of glucose counterregulation in humans.
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PMID:Fructose amplifies counterregulatory responses to hypoglycemia in humans. 1191 4

We have previously reported that specific counterregulatory responses to hypoglycemia were augmented by an infusion of fructose in nondiabetic humans. We hypothesized that this effect was due to the interaction of a "catalytic" dose of fructose with the regulatory protein for glucokinase in glucose-sensing cells that drive counterregulation. To examine whether fructose could restore counterregulatory responses in type 1 diabetic patients with defective counterregulation, we performed stepped hypoglycemic clamp studies (5.0, 4.4, 3.9, and 3.3 mmol/l glucose steps, 50 min each) in eight intensively treated patients (HbA(1c) 6.4 +/- 0.7%) on two separate occasions: without (control) or with coinfusion of fructose (1.2 mg . kg(-1) . min(-1)). Fructose induced a resetting of the glycemic threshold for secretion of epinephrine to higher plasma glucose concentrations (from 3.3 +/- 0.1 to 3.9 +/- 0.1 mmol/l; P = 0.001) and markedly augmented the increment in epinephrine (by 56%; P < 0.001). The amplification of epinephrine responses was specific; plasma norepinephrine, glucagon, growth hormone, and cortisol were unaffected. Hypoglycemia-induced endogenous glucose production ([3-(3)H]-glucose) rose by 90% (P < 0.001) in the fructose studies, compared with -2.0% (NS) in control. In concert, the glucose infusion rates during the 3.9- and 3.3-mmol/l steps were significantly lower with fructose (2.3 +/- 0.6 and 0.0 +/- 0.0 vs. 5.9 +/- 1.15 and 3.9 +/- 1.0 micromol . kg(-1) . min(-1), respectively; P < 0.001 for both), indicating the more potent counterregulatory response during fructose infusion. We conclude that infusion of fructose nearly normalizes the epinephrine and endogenous glucose production responses to hypoglycemia in type 1 diabetic patients with impaired counterregulation, suggesting that defects in these responses may be dependent on glucokinase-mediated glucose sensing.
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PMID:Fructose normalizes specific counterregulatory responses to hypoglycemia in patients with type 1 diabetes. 1573 34

Increased hepatic glucose output is one of the major mechanisms of hyperglycemia in diabetic patients. Fructose-2,6-bisphosphate (F-2,6-BP), a gluconeogenic intermediate, plays a critical role in hepatic glucose output by regulating gluconeogenesis and glycolysis in the liver. Brazilin, an active component of sappan wood (Caesalpinia sappan), decreases blood glucose in diabetic animals. In this study, the effect of brazilin on gluconeogenic intermediate production and enzyme activity were examined to investigate the hypoglycemic mechanism of brazilin. Brazilin increased the production of F-2,6-BP in hepatocytes by elevating intracellular levels of fructose-6-phosphate (F-6-P) and hexose-6-phosphate (H-6-P). Brazilin was also found to significantly increase the activity of 6-phosphofructo-2-kinase (PFK-2) and pyruvate kinase in glucagon-treated hepatocytes. However, glucose-6-phosphatase activity was not affected by brazilin. This data suggests that brazilin inhibits hepatic gluconeogenesis by elevating the F-2,6-BP level in hepatocytes, possibly by elevating cellular F-6-P/H-6-P levels and PFK-2 activity. Increased pyruvate kinase activity may also play a role in the anti-gluconeogenic action of brazilin.
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PMID:Effects of brazilin on the production of fructose-2,6-bisphosphate in rat hepatocytes. 1599 45

We studied the effect of fructose on hepatic conversion of amino-N to urea-N as quantified by the Capacity of Urea-N Synthesis (CUNS) determined in rats during alanine loading. There were 2 control groups, one without and one with infusion of somatostatin, in order to control the effects of insulin and glucagon. Somatostatin reduced CUNS from 8.5 +/- 0.5 mumol/(min x 100 g BW) to 6.3 +/- 0.3 mumol/(min x 100 g BW) (mean +/- SEM) (p < 0.01) and reduced glucagon concentrations by 75% (p<0.05). Insulin and glucose concentrations did not change. Fructose, at blood concentrations of about 1 mmol/l further reduced CUNS to 3.6 +/- 0.3 mumol/(min x 100 g BW) (p < 0.01). Insulin increased slightly (p < 0.05), but neither glucose nor glucagon changed. At increasing fructose concentrations up to 2 mmol/l there was no further effect on CUNS. Fructose in concentrations as used for parenteral nutrition and independent of glucoregulatory hormones, decreased hepatic amino acid catabolism.
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PMID:Effect of fructose on the capacity of urea-N synthesis in rats. 1684 92


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