Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of streptozotocin-induced diabetes mellitus on the activity of discrete regions of the brain were studied with histochemical localization and photodensitometric quantification of the metabolic enzyme, hexokinase. Two weeks after a single injection of streptozotocin (65 mg/kg, i.p.), plasma glucose and osmolarity levels were elevated, and plasma sodium concentrations were depressed. These changes were reversed in diabetic rats treated with insulin. Accompanying these symptoms of diabetes were significant increases in hexokinase activity in the magnocellular division of the paraventricular nucleus of the hypothalamus (mPVH, 12.1%), the medial subdivision of the nucleus of the tractus solitarius (mNTS, 15.5%), and the commissural subdivision of the NTS (cNTS, 10.9%). An increase, though just below the level of significance, was also observed in the supraoptic nucleus of the hypothalamus (SON, 11.5%). The increases in hexokinase activity were completely reversed in the cNTS (and SON) and only partly reversed in the mPVH and mNTS of insulin-treated diabetic rats. No changes in hexokinase activity were seen in the subfornical organ, medial preoptic area, parvocellular division of the PVH, locus coeruleus, or dorsal motor nucleus of the vagus of diabetic rats. These results reinforce the idea that the brain is not exempt from changes associated with diabetes mellitus and suggest that metabolic alterations in the mPVH (and SON) and two divisions of the NTS are likely related to changes in vasopressin production and blood volume, respectively.
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PMID:Alterations in brain hexokinase activity associated with streptozotocin-induced diabetes mellitus in the rat. 222 10

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

In mice with streptozotocin-induced diabetes of 3 days' duration, the hexokinase/glucose-6-phosphatase (HK/G6Pase) ratio in the kidney was enhanced by 52% (mean +/- SEM: 0.40 +/- 0.04 vs. 0.26 +/- 0.03; p less than 0.02) compared to control mice as a result of a 25% increase of HK (16.68 +/- 0.93 vs. 13.31 +/- 1.04 nmol/min/mg protein; p = 0.05) and a 17% decrease of G6Pase (42.51 +/- 2.75 vs. 51.25 +/- 1.89; p less than 0.05). In contrast, as expected, the corresponding ratio (HK + glucokinase/G6Pase) was strikingly reduced in the liver. In 9-day diabetic mice, the kidney enzyme changes were much smaller; however, in a chronic disease such as diabetes, even minimal deviations from the normal may lead to significant metabolic changes with time. The enhanced HK/G6Pase ratio in the diabetic kidney suggests an increase in glucose utilization. This may contribute to the increased synthesis of glycogen, glycoproteins (including basement membrane) and RNA (via provision of ribose-phosphate) occurring in the diabetic kidney and supports the view that the kidney (as opposed to other tissues) shows an 'anabolic response' to diabetes.
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PMID:Increased hexokinase/glucose-6-phosphatase ratio in the diabetic kidney as index of glucose overutilization. 255 19

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 effects of a beta-blocker, propranolol, on the enzyme and isoenzyme activities in the heart muscle in vitro and concomitant histopathology of the component cells of the islets of Langerhans were studied in the Wistar rats after treatment with streptozotocin and isoproterenol. The biochemical data indicated that the isoproterenol induced myocardial infarction (MI) precipitates an acute diabetic response in the rat heart. The superimposition of MI in diabetes mellitus caused significant inhibition of phosphofructokinase and hexokinase in the heart muscle. The lactate dehydrogenase depicted shifting of H-type to M-type in diabetes with or without MI. The drugs, when administered in combination, brought distinctive histopathological changes in beta-cells of the pancreatic islets including degranulation, hyalinosis and a near-total destruction; however A and D cells remained more or less unaffected. The effect of propranolol in diabetes mellitus was uncertain but in MI with or without prior diabetes, the drug inversely altered the activities of all the cardiac enzymes, besides stimulating a mild recuperation of the cells of the endocrine parenchyma.
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PMID:Myocardial dysfunction in diabetic rats: influence of beta-adrenoceptor blockade (propranolol). 263 86

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

Activities of hexokinase and glucose-6-phosphate dehydrogenase have been measured in red blood cells from control, diabetic and insulin treated rats. After an initial decrease, the enzyme activities increased, but remained lower than control levels. A reversal of the diabetes effect was seen with insulin administration. Insulin induced hypoglycemia increased both enzymes. An overall control of glucose metabolism by insulin in red blood cells was observed.
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PMID:Effect of diabetes and insulin-induced hypoglycemia on hexokinase and glucose-6-phosphate dehydrogenase in red blood cells. 267 46

The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P50(7.4] were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P50(7.4) values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2 affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.
Diabetes 1989 Jul
PMID:Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. 273 64

Glucose metabolism was investigated in two established clonal insulinoma cell lines (RINm5F and HIT) and in a newly developed line of mouse insulinoma cells (IgSV195). The hexokinase capacity in the homogenates of RINm5F cells was 22.1 +/- 3.23 U/g protein, but glucokinase was barely detectable (0.06 +/- 0.013 U/g protein). In contrast, both HIT and IgSV195 cells contained glucokinase (1.5 +/- 0.17 and 1.0 +/- 0.16 U/g protein, respectively) in addition to hexokinase activity. Glucose usage by the intact cells qualitatively reflected the glucose phosphorylation found in the cell-free extracts. RINm5F cells exhibited a high glucose usage rate with one high-affinity component, whereas both HIT and IgSV195 cells showed two components with different glucose affinities. HIT and IgSV195 cells may be useful for a model of pancreatic beta-cell glycolysis.
Diabetes 1988 May
PMID:Control of glucose phosphorylation and glucose usage in clonal insulinoma cells. 283 51

Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative-glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin.
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PMID:Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats. 293 94


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