Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study we measured the activity of some cytosolic enzymes involved in intracellular glucose metabolism in mononuclear leukocytes from 77 obese subjects of which 39 were nondiabetic and 38 had newly-diagnosed untreated type II diabetes mellitus. 28 subjects (19 nondiabetic and 18 diabetic) had also a study of insulin binding to monocytes. 35 subjects (14 nondiabetic, 21 diabetic) underwent an insulin tolerance test for the evaluation of in vivo insulin action. Mononuclear leukocytes from diabetic obese patients showed significantly lower activities of hexokinase (HK), 6-phosphofructokinase (PFK) and glucose-6-phosphate dehydrogenase (G6PDH), while pyruvate kinase (PK) and 6-phosphogluconate dehydrogenase (6PGDH) activities were similar in the two groups. In the whole population HK and G6PDH activities inversely correlated with fasting and 2-h OGTT plasma glucose levels. Neither plasma insulin levels nor maximal specific insulin binding to monocytes were significantly correlated with any of the enzyme activities measured. Conversely, the parameter of insulin action generated by insulin tolerance test significantly correlated with HK, G6PDH and 6PGDH. These results indicate that in obese subjects the presence of diabetes is associated with a reduced activity of some enzymes of glucose metabolism in mononuclear leukocytes. This multiple enzymatic defect is correlated with the impairment of in vivo insulin action.
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PMID:Mononuclear leukocytes from obese patients with type II diabetes have reduced activity of hexokinase, 6-phosphofructokinase and glucose-6-phosphate dehydrogenase. 847 54

Effects of dietary carbohydrates on triglyceride production and hepatic lipogenic enzyme activities were examined in Wistar fatty rats, an animal model of noninsulin dependent diabetes mellitus, fed fructose or glucose and were compared with those of Wistar lean rats. Carbohydrates were supplied in 10% drinking solutions for 21 days. As compared with lean rats, Wistar fatty rats were characterized by hyperglycemia, hyperinsulinemia and hypertriglyceridemia, the last of which was associated with an increased hepatic activity of fatty acid synthetase and an increased rate of triglyceride secretion from the liver to the circulation. Feeding fructose to genetically obese diabetic rats produced a threefold increase in the hepatic activity of fatty acid synthetase, a twofold increase in NADPH-generating enzymes (malic enzyme and glucose-6-phosphate dehydrogenase) and a 56% increase in the rate of triglyceride secretion, with a resultant 86% increase in plasma triglyceride concentrations. Feeding glucose produced a similar increase in the activity of NADPH-generating enzymes and triglyceride production in the fatty liver but it differed in producing no change in plasma triglyceride concentrations or hepatic fatty acid synthetase activity. Neither dietary fructose nor glucose changed glycemia or insulinemia. These results show that in genetically obese, diabetic rats feeding fructose and glucose is associated with an increase in hepatic lipogenic enzyme activities and triglyceride production, and suggest that fructose stimulates triglyceride production but impairs triglyceride removal, whereas glucose stimulates both of them.
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PMID:Effects of dietary fructose or glucose on triglyceride production and lipogenic enzyme activities in the liver of Wistar fatty rats, an animal model of NIDDM. 922 59

The prevalence of non insulin dependent diabetes mellitus (NIDDM) is increasing in all populations. This increment has been correlated with changes in lifestyle, particularly in eating behavior. Migration studies strongly suggest that NIDDM becomes more common when lifestyle factors interact with genetic susceptibility. Blacks have a higher prevalence of NIDDM than whites. In this study, it is suggested that persistent hyperglycemia mediated through the main carbohydrate of the Western diet-wheat, as white flour and whole wheat-in combination with partial or complete glucose 6-phosphate dehydrogenase deficiency are possible factors for the higher prevalence of NIDDM in blacks.
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PMID:Diet, diabetes, hypertension and blacks. 1042 Oct 90

Insulin regulates the rate of expression of many hepatic genes, including PEPCK, glucose-6-phosphatase (G6Pase), and glucose-6-phosphate dehydrogenase (G6PDHase). The expression of these genes is also abnormally regulated in type 2 diabetes. We demonstrate here that treatment of hepatoma cells with 5-aminoimidazole-4-carboxamide riboside (AICAR), an agent that activates AMP-activated protein kinase (AMPK), mimics the ability of insulin to repress PEPCK gene transcription. It also partially represses G6Pase gene transcription and yet has no effect on the expression of G6PDHase or the constitutively expressed genes cyclophilin or beta-actin. Several lines of evidence suggest that the insulin-mimetic effects of AICAR are mediated by activation of AMPK. Also, insulin does not activate AMPK in H4IIE cells, suggesting that this protein kinase does not link the insulin receptor to the PEPCK and G6Pase gene promoters. Instead, AMPK and insulin may lie on distinct pathways that converge at a point upstream of these 2 gene promoters. Investigation of the pathway by which AMPK acts may therefore give insight into the mechanism of action of insulin. Our results also suggest that activation of AMPK would inhibit hepatic gluconeogenesis in an insulin-independent manner and thus help to reverse the hyperglycemia associated with type 2 diabetes.
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PMID:5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. 1086 40

Free radical-induced lipid peroxidation has been associated with numerous disease processes including diabetes mellitus. The extent of lipid peroxidation (LPO) and antioxidant defense system [i.e., levels of glutathione (GSH), glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and catalase (CAT)] were evaluated in reticulocytes and erythrocytes of type 2 diabetic males and age-matched controls. Type 2 diabetics have shown increased lipid peroxidation and decreased levels of GSH, GR, GPx, G6PDH, and GST both in reticulocytes and erythrocytes compared to controls, indicating the presence of oxidative stress and defective antioxidant systems in these patients. CAT activity is found to be enhanced in both the reticulocytes and erythrocytes of diabetics, with a greater percentage enhancement in reticulocytes. The extent of increase in lipid peroxidation is greater in erythrocytes compared to reticulocytes in these patients. Furthermore, the maturation of reticulocytes to erythrocytes resulted in decreased GSH and decreased activities of all antioxidant enzymes (except CAT) both in normals and type 2 diabetes individuals, indicating decreased scavenging capacity as reticulocytes mature to erythrocytes. These maturational alterations are further intensified in type 2 diabetics. The present study reveals that the alterations in lipid peroxidation and antioxidant system lean toward early senescence of erythrocytes in type 2 diabetic patients.
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PMID:The antioxidant status during maturation of reticulocytes to erythrocytes in type 2 diabetics. 1285 69

Several links relate mitochondrial metabolism and type 2 diabetes or chronic hyperglycaemia. Among them, ATP synthesis by oxidative phosphorylation and cellular energy metabolism (ATP/ADP ratio), redox status and reactive oxygen species (ROS) production, membrane potential and substrate transport across the mitochondrial membrane are involved at various steps of the very complex network of glucose metabolism. Recently, the following findings (1) mitochondrial ROS production is central in the signalling pathway of harmful effects of hyperglycaemia, (2) AMPK activation is a major regulator of both glucose and lipid metabolism connected with cellular energy status, (3) hyperglycaemia by inhibiting glucose-6-phosphate dehydrogenase (G6PDH) by a cAMP mechanism plays a crucial role in NADPH/NADP ratio and thus in the pro-oxidant/anti-oxidant cellular status, have deeply changed our view of diabetes and related complications. It has been reported that metformin has many different cellular effects according to the experimental models and/or conditions. However, recent important findings may explain its unique efficacy in the treatment of hyperglycaemia- or insulin-resistance related complications. Metformin is a mild inhibitor of respiratory chain complex 1; it activates AMPK in several models, apparently independently of changes in the AMP-to-ATP ratio; it activates G6PDH in a model of high-fat related insulin resistance; and it has antioxidant properties by a mechanism (s), which is (are) not completely elucidated as yet. Although it is clear that metformin has non-mitochondrial effects, since it affects erythrocyte metabolism, the mitochondrial effects of metformin are probably crucial in explaining the various properties of this drug.
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PMID:Mitochondrial metabolism and type-2 diabetes: a specific target of metformin. 1450 5

A 58-year-old woman was admitted at diagnosis of type 2 diabetes without keto-acidosis. Blood glucose was normalized initially with insulin. Whilst taking glibenclamide, she developed acute haemolysis. She was homozygous for glucose-6-phosphate dehydrogenase (G6PD) deficiency and had no other factors predisposing haemolysis. We reviewed the literature and discuss the relationship between glibenclamide and haemolytic crisis and between G6PD-deficiency and diabetes.
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PMID:Glibenclamide-induced acute haemolytic anaemia revealing a G6PD-deficiency. 1512 5

The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin combination treatment on circulatory lipids, lipoproteins and lipid peroxidation markers were studied in neonatal streptozotocin (nSTZ) non-insulin dependent diabetic rats. Non-insulin dependent diabetes mellitus (NIDDM) was induced by a single dose injection of streptozotocin (100 mg kg(-1), i. p.) to two-day-old rats. After 10-12 weeks, rats weighing above 150 g were selected for screening for the NIDDM model. The rats were checked for fasting blood glucose levels to confirm the status of NIDDM. NBDP (50,100 or 200 mg kg(-1) ) was administered orally for six weeks to the confirmed diabetic rats (to evaluate the effective dose). The levels of serum lipids and lipid peroxidation markers were significantly increased, whilst the activity of glucose-6-phosphate dehydrogenase was significantly decreased in nSTZ diabetic rats. NBDP and metformin were able to restore the altered serum lipids, lipoproteins, lipid peroxidation marker levels and glucose-6-phosphate dehydrogenase activity to almost control levels. The results showed the antihyperlipidaemic properties of NBDP and metformin in addition to its antidiabetic action. Combination treatment was more effective then either drug alone. The results indicated that the coadministration of NBDP with metformin to nSTZ diabetic rats normalized blood glucose and caused marked improvement in altered serum lipids, lipoproteins and lipid peroxidation markers during diabetes. The data indicated that NBDP represented an effective antihyperglycaemic and antihyperlipidaemic adjunct for the treatment of diabetes, and may be a potential source of new orally active agents for future therapy.
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PMID:Effect of N-benzoyl-D-phenylalanine on streptozotocin-induced changes in the lipid and lipoprotein profile in rats. 1580 92

In adipocytes, oxidative stress and chronic inflammation are closely associated with metabolic disorders, including insulin resistance, obesity, cardiovascular disease, and type 2 diabetes. However, the molecular mechanisms underlying these metabolic disorders have not been thoroughly elucidated. In this report, we demonstrate that overexpression of glucose-6-phosphate dehydrogenase (G6PD) in adipocytes stimulates oxidative stress and inflammatory responses, thus affecting the neighboring macrophages. Adipogenic G6PD overexpression promotes the expression of pro-oxidative enzymes, including inducible nitric oxide synthase and NADPH oxidase, and the activation of nuclear factor-kappaB (NF-kappaB) signaling, which eventually leads to the dysregulation of adipocytokines and inflammatory signals. Furthermore, secretory factors from G6PD-overexpressing adipocytes stimulate macrophages to express more proinflammatory cytokines and to be recruited to the adipocytes; this would cause chronic inflammatory conditions in the adipose tissue of obesity. These effects of G6PD overexpression in adipocytes were abolished by pretreatment with NF-kappaB inhibitors or antioxidant drugs. Thus, we propose that a high level of G6PD in adipocytes may mediate the onset of metabolic disorders in obesity by increasing the oxidative stress and inflammatory signals.
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PMID:Increase in glucose-6-phosphate dehydrogenase in adipocytes stimulates oxidative stress and inflammatory signals. 1706 29

This study investigated the effect of aqueous and ethanol soluble solid extracts of guava (Psidium guajava Linn.) leaves on hypoglycemia and glucose metabolism in type 2 diabetic rats. Low-dose streptozotocin (STZ) and nicotinamide were injected into Sprague-Dawley (SD) rats to induce type 2 diabetes. Acute and long-term feeding tests were carried out, and an oral glucose tolerance test (OGTT) to follow the changes in plasma glucose and insulin levels was performed to evaluate the antihyperglycemic effect of guava leaf extracts in diabetic rats.The results of acute and long-term feeding tests showed a significant reduction in the blood sugar level in diabetic rats fed with either the aqueous or ethanol extract of guava leaves (p < 0.05). Long-term administration of guava leaf extracts increased the plasma insulin level and glucose utilization in diabetic rats. The results also indicated that the activities of hepatic hexokinase, phosphofructokinase and glucose-6-phosphate dehydrogenase in diabetic rats fed with aqueous extracts were higher than in the normal diabetic group (p < 0.05). On the other hand, diabetic rats treated with the ethanol extract raised the activities of hepatic hexokinase and glucose-6-phosphate dehydrogenase (p < 0.05) only. The experiments provided evidence to support the antihyperglycemic effect of guava leaf extract and the health function of guava leaves against type 2 diabetes.
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PMID:Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats. 1881 64


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