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)

This paper reports on the effect of GCP-02, a dual activator of the peroxisome proliferator-activated receptors alpha/gamma (PPARalpha/gamma), on glucose and lipid metabolism in insulin-resistant obese mice induced by monosodium glutamate. The mice were divided into four groups on the basis of treatment: control group, rosiglitazone (positive control) (7 micromol/kg), and low- and high-dosage GCP-02 (7 micromol/kg and 3.5 micromol/kg, respectively). Drugs were given orally once a day for 19 days, and mice underwent testing for insulin tolerance, oral glucose tolerance and gluconeogenesis, and plasma cholesterol, triglyceride and free fatty acid levels. Mice were sacrificed, and body length and weight were measured; intraperitoneal adipose, heart and liver weighed; and plasma alanine aminotransferase (ALT) level and aspartate aminotransferase (AST) activity measured. Liver, soleus muscle and myocardium were assayed for glycogen, triglyceride and free fatty acid content and myocardia tested for superoxide dismutase (SOD) activity and malonaldehyde content. RT-PCR revealed expression of insulin receptor substrate 1 and 2 (IRS1, IRS2) and related genes in liver. GCP-02 had a more powerful effect than rosiglitazone on improving insulin sensitivity, ameliorating glucose tolerance, suppressing L-alanine-induced gluconeogenesis, and decreasing plasma levels of cholesterol, triglyceride and free fatty acid. It reduced body weight in control mice, significantly lowered hepatic content of glycogen, triglyceride and free fatty acid and myocardial content of triglyceride, and increased myocardial SOD activity. IRS2 mRNA was down-regulated in control mice but up-regulated by GCP-02. Thus, GCP-02 is a potential candidate for the prevention and therapy of diseases associated with insulin resistance such as type 2 diabetes mellitus and cardiovascular disease.
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PMID:Effect of GCP-02, a PPARalpha/gamma dual activator, on glucose and lipid metabolism in insulin-resistant mice. 1804 28

Substantial data indicate that oxidative stress is involved in the development of diabetic retinopathy. Two candidate genes that affect the oxidative stress are manganese mitochondrial superoxide dismutase (Mn-SOD) and endothelial nitric oxide synthase (eNOS). The aim of the present study was to examine the role of the V16A polymorphism of the Mn-SOD gene and the 4a/b polymorphism of the eNOS gene in the development of diabetic retinopathy in Caucasians with type 2 diabetes. In this cross sectional case-control study 426 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 283 patients with diabetic retinopathy and the control group of 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. A significantly higher frequency of the VV genotype of the V16A polymorphism of the Mn-SOD was found in patients with diabetic retinopathy compared to those without diabetic retinopathy (OR=2.1, 95% whereas the 4a/b polymorphism of the eNOS gene failed to yield an association with diabetic retinopathy. We may conclude that the VV genotype of the V16A polymorphism of the Mn-SOD gene was associated with diabetic retinopathy in Caucasians with type 2 diabetes, therefore it might be used as a genetic marker of diabetic retinopathy in Caucasians.
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PMID:Manganese superoxide dismutase gene polymorphism (V16A) is associated with diabetic retinopathy in Slovene (Caucasians) type 2 diabetes patients. 1805 37

This study aimed to investigate the interrelationship of plasma lipid profile, lipid peroxidation, and erythrocyte antioxidative defense in patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Plasma levels of total cholesterol, triglycerides, and lipid peroxides and the activities of copper, zinc superoxide dismutase (CuZnSOD), catalase, glutathione peroxidase (GSH-Px), as well as the amount of glutathione in erythrocytes, were determined in IDDM, NIDDM, and nondiabetic control subjects. Additionally, morphology of erythrocytes in all subjects was examined. Plasma levels of total cholesterol and triglycerides were significantly increased in NIDDM compared with controls. Also, the lipid peroxide level was higher in NIDDM than in either control or IDDM subjects. CuZnSOD activity in erythrocytes was elevated in NIDDM patients compared with the control. In NIDDM patients, more extensive erythrocyte spherocytosis and echinocytosis compared with both control and IDDM subjects were observed. In contrast with the IDDM group, the observed abnormality in lipid metabolism in NIDDM patients is closely associated with increased lipid peroxidation, changes in antioxidative defense, and erythrocyte morphology.
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PMID:Interrelationship of antioxidative status, lipid peroxidation, and lipid profile in insulin-dependent and non-insulin-dependent diabetic patients. 1806

Reduced insulin sensitivity is a key factor in the pathogenesis of type 2 diabetes and hypertension. Skeletal muscle insulin resistance is particularly important for its major role in insulin-mediated glucose disposal. Angiotensin II (ANG II) is integral in regulating blood pressure and plays a role in the pathogenesis of hypertension. In addition, we have documented that ANG II-induced skeletal muscle insulin resistance is associated with generation of reactive oxygen species (ROS). However, the linkage between ROS and insulin resistance in skeletal muscle remains unclear. To explore potential mechanisms, we employed the transgenic TG(mRen2)27 (Ren-2) hypertensive rat, which harbors the mouse renin transgene and exhibits elevated tissue ANG II levels, and skeletal muscle cell culture. Compared with Sprague-Dawley normotensive control rats, Ren-2 skeletal muscle exhibited significantly increased oxidative stress, NF-kappaB activation, and TNF-alpha expression, which were attenuated by in vivo treatment with an angiotensin type 1 receptor blocker (valsartan) or SOD/catalase mimetic (tempol). Moreover, ANG II treatment of L6 myotubes induced NF-kappaB activation and TNF-alpha production and decreased insulin-stimulated Akt activation and GLUT-4 glucose transporter translocation to plasma membranes. These effects were markedly diminished by treatment of myotubes with valsartan, the antioxidant N-acetylcysteine, NADPH oxidase-inhibiting peptide (gp91 ds-tat), or NF-kappaB inhibitor (MG-132). Similarly, NF-kappaB p65 small interfering RNA reduced NF-kappaB p65 subunit expression and nuclear translocation and TNF-alpha production but improved insulin-stimulated phosphorylation (Ser(473)) of Akt and translocation of GLUT-4. These findings suggest that NF-kappaB plays an important role in ANG II/ROS-induced skeletal muscle insulin resistance.
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PMID:Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-kappaB activation via NADPH oxidase. 1807 21

The objective of this paper is to evaluate adaptations in hepatic mitochondrial protein mass, function and efficiency in a rat model of high-fat diet-induced obesity and insulin resistance that displays several correlates to human obesity. Adult male rats were fed a high-fat diet for 7 weeks. Mitochondrial state 3 and state 4 respiratory capacities were measured in liver homogenate and isolated mitochondria by using nicotinamide adenine dinucleotide, flavin adenine dinucleotide and lipid substrates. Mitochondrial efficiency was evaluated by measuring proton leak kinetics. Mitochondrial mass was assessed by ultrastructural observations and citrate synthase (CS) activity measurements. Mitochondrial oxidative damage and antioxidant defence were also considered by measuring lipid peroxidation, aconitase and superoxide dismutase (SOD) specific activity. Whole body metabolic characteristics were obtained by measuring 24-h oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory quotient (RQ) and nonprotein respiratory quotient (NPRQ), using indirect calorimetry with urinary nitrogen analysis. Whole body glucose homeostasis was assessed by measuring plasma insulin and glucose levels after a glucose load. Adult rats fed a high-fat diet for 7 weeks, exhibit not only obesity, insulin resistance and hepatic steatosis, but also reduced respiratory capacity and increased oxidative stress in liver mitochondria. Our present results indicate that alterations in the mitochondrial compartment induced by a high-fat diet are associated with the development of insulin resistance and ectopic fat storage in the liver. Our results thus fit in with the emerging idea that mitochondrial dysfunction can led to the development of metabolic diseases, such as obesity, type 2 diabetes mellitus and nonalcoholic steatohepatitis.
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PMID:Alterations in hepatic mitochondrial compartment in a model of obesity and insulin resistance. 1827 91

Metallothionein (MT) as a potent antioxidant can affect energy metabolism. The present study was undertaken to investigate the association between MT gene polymorphism and type 2 diabetes mellitus. Using the PCR-based restriction fragment length polymorphism method, seven single nucleotide polymorphisms (SNPs) in MT genes (rs8052394 and rs11076161 in MT1A gene, rs8052334, rs964372, and rs7191779 in MT1B gene, rs708274 in MT1E gene, and rs10636 in MT2A gene) were detected in 851 Chinese people of Han descent (397 diabetes and 454 controls). Several serum measurements were also examined randomly for 43 diabetic patients and 41 controls. The frequency distributions of the G allele in SNP rs8052394 of MT1A gene were significantly associated with the incidence of type 2 diabetes. There was no difference between patients and controls for the rest of six SNPs. Serum levels of interleukin-6 and tumor necrosis factor-alpha were higher, and serum superoxide dismutase activity was significantly lower in the diabetic group than those in the control group. For diabetic patients, serum superoxide dismutase activity was significantly lower in GG or GA carriers than those of AA carriers of rs8052394 SNP. Increased serum levels in diabetic patients were positively associated with rs964372 SNP, and type 2 diabetes with neuropathy was positively associated with rs10636 and rs11076161. These results suggest that multiple SNPs in MT genes are associated with diabetes and its clinical symptoms. Furthermore, MT1A gene in rs8052394 SNP is most likely the predisposition gene locus for diabetes or changes of serum superoxide dismutase activity.
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PMID:Polymorphisms in metallothionein-1 and -2 genes associated with the risk of type 2 diabetes mellitus and its complications. 1834 10

In this paper, the antidiabetic effects of cysteinyl metformin (CM), a newly synthesized agent, were investigated to evaluate the hypoglycemic/hypolipidemic effects by measuring blood glucose, triglyceride and insulin levels in CM- and metformin-treated diabetic rats. Two diabetic models were used: (1) an alloxan-induced model in which diabetes was produced by alloxan (200 mg/kg, i.p.), then rats were treated with CM (300, 100 and 33 mg/kg) for 14 days; (2) a streptozocin-induced model in which diabetes was produced by streptozocin (30 mg/kg, i.p.) and a sustained high lipid diet, then rats were treated with CM for 8 weeks. The hypoglycemic effect of CM exceeded that of metformin while the hypolipidemic effect was similar. In addition, CM increased the blood insulin level of the alloxan-induced experimental animals (which had an insulin deficiency), but reduced the insulin level of the streptozocin-induced animals (which had an insulin excess), suggesting that CM improves pancreatic beta-cell function. The effects of CM, metformin and cysteine on the antioxidant defense system in alloxan-induced rats were also studied. The serum malondialdehyde (MDA) level was determined to provide evidence for lipid peroxidation, All the groups of animals given CM, metformin and cysteine exhibited less severe oxidative stress than the diabetic group. Then, several key antioxidants such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and the pancreatic exocrine enzyme amylase (AMS) were measured. CM restored the activity of all these agents to nearly normal values while metformin and cysteine merely restored the activity of SOD. At the end of our study, the animals were sacrificed by decapitation and the liver, kidney and pancreas were weighed to allow investigation of organ edema. The results obtained showed that CM corrected the organ edema of the diabetic rats. All these findings suggested that CM has a protective effect on the antioxidant defense system and beta-cell dysfunction in alloxan-induced diabetic rats. All these results suggest that CM is a potential candidate for the future treatment of both type 1 and type 2 diabetes.
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PMID:The antidiabetic effects of cysteinyl metformin, a newly synthesized agent, in alloxan- and streptozocin-induced diabetic rats. 1837 84

The possible contribution of early changes in lipid composition, function, and antioxidant status of abdominal adipose tissue (AAT) induced by a fructose-rich diet (FRD) to the development of insulin resistance (IR) and oxidative stress (OS) was studied. Wistar rats were fed with a commercial diet with (FRD) or without 10% fructose in the drinking water for 3 weeks. The glucose (G), triglyceride (TG), and insulin (I) plasma levels, and the activity of antioxidant enzymes, lyposoluble antioxidants, total glutathione (GSH), lipid peroxidation as TBARS, fatty acid (FA) composition of AAT-TG as well as their release by incubated pieces of AAT were measured. Rats fed with a FRD have significantly higher plasma levels of G, TG, and I. Their AAT showed a marked increase in content and ratios of saturated to monounsaturated and polyunsaturated FAs, TBARS, and catalase, GSH-transferase and GSH-reductase, together with a decrease in superoxide dismutase and GSH-peroxidase activity, and total GSH, alpha-tocopherol, beta-carotene and lycopene content. Incubated AAT from FRD released in vitro higher amount of free fatty acids (FFAs) with higher ratios of saturated to monounsaturated and polyunsaturated FAs. Our data suggest that FRD induced an early prooxidative state and metabolic dysfunction in AAT that would favor the overall development of IR and OS and further development of pancreatic beta-cell failure; therefore, its early control would represent an appropriate strategy to prevent alterations such as the development of type 2 diabetes.
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PMID:Abdominal adipose tissue: early metabolic dysfunction associated to insulin resistance and oxidative stress induced by an unbalanced diet. 1862 97

Regulation of coronary function in diabetic hearts is an important component in preventing ischemic cardiac events but remains poorly studied. Exercise is recommended in the management of diabetes, but its effects on diabetic coronary function are relatively unknown. We investigated coronary artery myogenic tone and endothelial function, essential elements in maintaining vascular fluid dynamics in the myocardium. We hypothesized that exercise reduces pressure-induced myogenic constriction of coronary arteries while improving endothelial function in db/db mice, a model of type 2 diabetes. We used pressurized mouse coronary arteries isolated from hearts of control and db/db mice that were sedentary or exercised for 1 h/day on a motorized exercise-wheel system (set at 5.2 m/day, 5 days/wk). Exercise caused a approximately 10% weight loss in db/db mice and decreased whole body oxidative stress, as measured by plasma 8-isoprostane levels, but failed to improve hyperglycemia or plasma insulin levels. Exercise did not alter myogenic regulation of arterial diameter stimulated by increased transmural pressure, nor did it alter smooth muscle responses to U-46619 (a thromboxane agonist) or sodium nitroprusside (an endothelium-independent dilator). Moderate levels of exercise restored ACh-simulated, endothelium-dependent coronary artery vasodilation in db/db mice and increased expression of Mn SOD and decreased nitrotyrosine levels in hearts of db/db mice. We conclude that the vascular benefits of moderate levels of exercise were independent of changes in myogenic tone or hyperglycemic status and primarily involved increased nitric oxide bioavailability in the coronary microcirculation.
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PMID:Exercise restores coronary vascular function independent of myogenic tone or hyperglycemic status in db/db mice. 1864 Dec 79

An investigation was made to evaluate the role of Anethum graveolens L. (dill) leaf extract in the regulation of corticosteroid-induced type 2 diabetes mellitus in female rats. In dexamethasone-treated animals (1 mg/kg for 22 days) an increase in serum concentration of insulin and glucose and in hepatic lipid peroxidation (LPO) was observed. However, there was a decrease in serum concentration of thyroid hormones and in the endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) in liver. In animals treated with an equivalent amount of dexamethasone for a similar period (22 days) when received the leaf extract (100 mg/kg b.wt/d.) for last 15 days a decrease in the concentration of both serum glucose and insulin was observed, indicating the potential of the plant extract in the regulation of corticosteroid-induced diabetes. Dexamethasone-induced alterations in the levels of thyroid hormones as well as in hepatic LPO, SOD, CAT and GSH were also reversed by the plant extract.
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PMID:The effect of Anethum graveolens L. (dill) on corticosteroid induced diabetes mellitus: involvement of thyroid hormones. 1881 8


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