Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.1 (hexokinase)
5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the myocardium is capable of utilizing both glucose and fatty acid substrates, glucose metabolism is inhibited in the presence of fatty acid during normal perfusion conditions. Fatty acid regulation of glucose utilization in intact beating rat hearts was studied with 13C-enriched substrates and 13C and 31P NMR spectroscopy at 8.5 T. During [1-13C]glucose and insulin perfusion, the 13C appeared in alanine, lactate and the glutamate isotopomers, indicating glycolytic flux through pyruvate and glucose-supported tricarboxylic acid (TCA) cycle oxidation, respectively. Following the addition of hexanoic acid, 1 mM, [1-13C]glucose metabolism proceeded through the hexokinase and phosphofructokinase reactions, as evidenced by continued production of [3-13C]alanine and [3-13C]lactate, but was completely inhibited at the pyruvate dehydrogenase (PDH) reaction as evidenced by a lack of appearance of the 13C label in the glutamate isotopomers. This inhibition of PDH was associated with increased PCr/ATP levels and was readily reversed by removal of hexanoic acid. Addition of dichloroacetate, 5 mM, which increases the active form of PDH, to fatty acid and glucose containing perfusate reinstituted carbon flux through the PDH reaction, indicating that the mechanism of fatty acid cessation of PDH flux is by reversible inactivation of the PDH enzyme complex. Thus the point of inhibition and mechanism of action of fatty acid modulation of glucose metabolism can be continuously and non-destructively studied in the intact beating heart with 13C and 31P NMR and is primarily attributable, in this model, to reversible PDH enzyme inactivation.
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PMID:Fatty acid regulation of glucose metabolism in the intact beating rat heart assessed by carbon-13 NMR spectroscopy: the critical role of pyruvate dehydrogenase. 252 40

The effect of type I (insulin-dependent) diabetes mellitus on the key glycolytic enzymes of red cells was studied. The activities of hexokinase, phosphofructokinase and pyruvate kinase were found to be significantly (p less than 0.01) increased in diabetic patients. Treatment with insulin restored the enzyme activities to normal. The increased activities of the key enzymes may help to regulate red cell ATP level in response to the elevated Na:K pump rate in diabetes. The increased activities of these enzymes may also be due to a greater proportion of young erythrocytes in diabetic patients because of a shortened red cell life span as compared to normal.
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PMID:Effect of type I (insulin-dependent) diabetes mellitus on key glycolytic enzymes of red blood cells. 253 57

Glyceraldehyde has been known to be an insulin secretagogue for more than 15 years. It has been (reasonably) assumed that glyceraldehyde enters the glycolytic pathway via its phosphorylation by ATP to form glyceraldehyde phosphate, a reaction catalyzed by the enzyme triokinase, and that subsequent metabolism is identical to that of glucose. glucose. However, up to now there have been no studies verifying the presence of triokinase in the pancreatic beta cell. We report here that (1) the activity of triokinase in pancreatic islets is very low, indicating that the activity is intrinsically low and/or the enzyme was rapidly inactivated during the preparation of tissue for assay; (2) the activity is much lower than glucose phosphorylating activity (hexokinase plus glucokinase) in islets, even though glyceraldehyde is a more efficient insulin secretagogue than glucose; (3) glyceraldehyde phosphate dehydrogenase from pancreatic islets can use glyceraldehyde as a substrate in place of glyceraldehyde phosphate (the Vmax of glyceraldehyde phosphate dehydrogenase from islets when glyceraldehyde is the substrate is 20-fold that of triokinase when glyceraldehyde is the substrate); and (4) the Km of glyceraldehyde phosphate dehydrogenase with respect to glyceraldehyde (4.8 mM) is similar to the concentration of glyceraldehyde that gives one-half maximal rates of insulin release from pancreatic islets, whereas the Km of triokinase with respect to glyceraldehyde is much lower (less than 50 microM). These data suggest that besides stimulating insulin release in islets via its entering metabolism by phosphorylation to glyceraldehyde phosphate in the triokinase reaction, glyceraldehyde could be phosphorylated by Pi in the glyceraldehyde phosphate dehydrogenase reaction to form glycerate 1-phosphate which is probably unmetabolizable in islets. The second reaction could drastically increase the NADH/NAD ratio in islets without providing substrates for hydrogen shuttles that reoxidize cytosolic NADH. Since an increased NAD(P)H/NAD(P) ratio is believed to be a key part of the signal for insulin release, such a mechanism would explain the potent insulinotropism of glyceraldehyde in short-term experiments. In addition, the formation of unmetabolizable acids may explain the toxic effects of long-term exposure of islets to glyceraldehyde and why glyceraldehyde causes the beta cell to become acidic, whereas glucose does not.
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PMID:Does glyceraldehyde enter pancreatic islet metabolism via both the triokinase and the glyceraldehyde phosphate dehydrogenase reactions? A study of these enzymes in islets. 253 42

Alloxan diabetes induced in white rats by intraperitoneal injection of alloxan-monohydrate (15 mg/100 g body weight) was used to study changes in the glycogen phosphorylase a and b, phosphoprotein phosphatases and hexokinase activities under insulin deficiency conditions. Among the enzymes studied, an increase in muscle phosphorylase a activity as well as the a/b ratio have been obtained. In diabetic muscle phosphoprotein phosphatases and hexokinase activities were diminished. AMP increased the liver glycogen phosphorylase activity twice in diabetic rats whereas in normal animals the enzyme was less sensitive to this effector. The changes in liver hexokinase activity at diabetes were not connected and correlated with the altered phosphorylase and protein phosphatase activities. The logical chain of probable molecular events taking place in muscle glycogen metabolism under the conditions of insulin deficiency is offered.
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PMID:Changes in the activity of enzymes, participating in glycogen metabolism of alloxan diabetic rats. 255 79

The activities of the hepatic glycolytic enzymes glucokinase (GKase) and hexokinase (HKase) in herbivorous Microtus arvalis were very low and the hepatic fructose-1,6-diphosphatase (FDPase) activities were almost the same as those in C57BL/6J mice. Glycosuria was observed in over 50% of voles fed on a low fibre, high concentrate diet. Voles with a high incidence of glycosuria for over 6 weeks became insulin deficient. In these diabetic voles, the hepatic GKase, HKase and FDPase activities decreased considerably as a result of diminished insulin secretion and fatty degeneration of the hepatic cells. It was considered that M. arvalis would be a useful animal model in which to study disorders of glucose utilization in herbivora.
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PMID:Hepatic enzyme activities and plasma insulin concentrations in diabetic herbivorous voles. 256 Oct 34

A dimethoxy derivative of leucocyandin 3-O-beta-D-galactosyl cellobioside isolated from the bark of F. bengalensis Linn demonstrated antidiabetic action. On oral administration, it decreased blood sugar very significantly both in normal and moderately diabetic rats and increased serum insulin significantly in the latter at a dosage of 250 mg/kg for a 2 hr period. During one month treatment of the diabetic rats orally with the active principle, at a dosage of 100 mg/kg, there was a significant decrease in blood and urine sugar, certain lipid components in serum and tissues and glucose-6-phosphatase activity in liver, but significant increase in body weight and the activities of hexokinase and HMGCOA reductase in tissues as compared to diabetic control. The mechanism of action of the principle may be related to its protective/inhibitory action against the insulin degradative processes.
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PMID:Antidiabetic effect of a leucocyanidin derivative isolated from the bark of Ficus bengalensis Linn. 263 65

In rat pancreatic islets the effects of cholecystokinin octapeptide (CCK-8) on pentose phosphate shunt (PPS) activity, glucokinase and hexokinase activity, and NADPH, NADP+, NADH, and NAD+ were studied. By elevating the glucose concentration from 3.0 to 8.3 and 16.7 mM the oxidation of [1-14C]- and [6-14C]glucose and the calculated PPS activity were increased in a concentration-dependent manner; 10 nM CCK-8 enhanced selectively the effect on [1-14C]glucose oxidation thereby increasing the PPS activity but only at an intermediate glucose concentration (8.3 mM). CCK-8 had no effect on glucokinase or hexokinase activity and CCK-8 did not influence glucose utilization. By elevating the glucose concentration, total NADPH and NADH were increased and total NADP+ and NAD+ were decreased. CCK-8 (10 nM) increased selectively NADPH and decreased NADP+ but did not change NADH or NAD+; the effect of CCK-8 on NADPH and NADH was only observed in the presence of an intermediate stimulatory glucose concentration (8.3 mM) but not at either a substimulatory glucose concentration or a maximally stimulatory glucose concentration for insulin release (3.0 or 16.7 mM). The data indicate first that CCK-8 does not act on glucose phosphorylation or glucose utilization and second that CCK-8 increases PPS activity and NADPH levels in rat pancreatic islets. Since the concentrations of glucose necessary for these CCK-8 effects are in the range of 8.3 mM and parallel with those necessary for insulin release as shown in earlier observations, glucose oxidation via pentose phosphate shunt and NADPH are suggested to be related to the CCK-8-modulated insulin release.
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PMID:Effect of CCK-8 on pentose phosphate shunt activity, pyridine nucleotides, and glucokinase of rat islets. 264 44

Significant hypertrophy of the adrenal glands was observed in Wistar rats the day after a single prodigiozan administration. This did not change the level of glucocorticoids in blood serum, but increased the concentration in insulin. Analysis of steroidogenesis in the adrenal glands indicated significant increase in steroid's production in the experimental group of rats as compared to the control. An increase of glucoso-6-phosphate dehydrogenase and hexokinase activity in adrenal tissue was also observed. The results suggest that stimulation of corticosteroid's secretion was accompanied by an increase in their reception to tissues which caused an increase of nonspecific resistance of the organism.
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PMID:[Effect of prodigiozan on the glucocorticoid and insulin ratio in the blood serum of white rats]. 265 49

Aconitan A did not affect plasma insulin levels in normal, glucose-loaded and alloxan-induced hyperglycemic mice and gave no influence on insulin binding to isolated adipocytes. Aconitan A exerted no effect on the activities of hepatic hexokinase, glucokinase, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase, whereas it significantly increased hepatic phosphofructokinase activity. Although the activity of hepatic glycogen synthetase showed a tendency to increase, the activity of liver phosphorylase and glycogen content were unchanged by aconitan A. Aconitan A did not change the total cholesterol and triglyceride contents of plasma and liver.
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PMID:Mechanisms of hypoglycemic activity of aconitan A, a glycan from Aconitum carmichaeli roots. 266 53

The early stages of insulin-dependent diabetes mellitus are characterized by a selective inability to secrete insulin in response to glucose, coupled to a better response to nonnutrient secretagogues. The deficient glucose response may be a result of the autoimmune process directed toward the beta-cells. Interleukin-1 (IL-1) has been suggested to be one possible mediator of immunological damage of the beta-cells. In the present study we characterized the sensitivity of beta-cells to different secretagogues after human recombinant IL-1 beta (rIL-1 beta) exposure. Furthermore, experiments were performed to clarify the biochemical mechanisms behind the defective insulin response observed in these islets. Rat pancreatic islets were isolated and kept in tissue culture (medium RPMI-1640 plus 10% calf serum) for 5 days. The islets were subsequently exposed to 60 pM human recombinant IL-1 beta during 48 h in the same culture conditions as above and examined immediately after IL-1 exposure. The rIL-1 beta-treated islets showed a marked reduction of glucose-stimulated insulin release. Stimulation with arginine plus different glucose concentrations, and leucine plus glutamine partially counteracted the rIL-1 beta-induced reduction of insulin release. The activities of the glycolytic enzymes hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in control and IL-1-exposed islets. Treatment with IL-1 also did not impair the activities of NADH+- and NADPH+-dependent glutamate dehydrogenase, glutamate-aspartate transaminase, glutamate-alanine transaminase, citrate synthase, and NAD+-linked isocitrate dehydrogenase. The oxidation of D-[6-14C]glucose and L-[U-14C]leucine were decreased by 50% in IL-1-treated islets. Furthermore, there was a significant decrease in the ratios of [2-14C]pyruvate oxidation/[1-14C]pyruvate decarboxylation and L-[U-14C]leucine oxidation/L-[1-14C]leucine decarboxylation, indicating that IL-1 decreases the proportion of generated acetyl-coenzyme-A residues undergoing oxidation. However, in the presence of IL-1 there was a significant increase in L-[U-14C]glutamate oxidation. These combined observations suggest that exposure to IL-1 induces a preferential decrease in glucose-mediated insulin release and mitochondrial glucose metabolism. This mitochondrial dysfunction seems to reflect an impairment in proximal steps of the Krebs cycle. It is conceivable that the IL-1-induced suppression and shift in islet metabolism can be an explanation for the beta-cell insensitivity to glucose observed in the early phases of human and experimental insulin-dependent diabetes mellitus.
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PMID:Differential sensitivity to beta-cell secretagogues in cultured rat pancreatic islets exposed to human interleukin-1 beta. 266 6


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