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)

We evaluate the influence of the time interval from the last meal on the blood glucose response to exercise in men with type 2 diabetes. Nineteen men with type 2 diabetes participated in an exercise training program carried out at 60% of maximal oxygen uptake (VO2peak) for 1 h, 3 times a week. Capillary whole blood glucose was measured immediately before and after each exercise session, and the time interval from the last meal (breakfast, lunch, or dinner) was recorded. Seven time intervals were considered (fasted overnight and 0-1, 1-2, 2-3, 3-4, 4-5, and 5-8 h postmeal). A total of 1,045 exercise sessions were analyzed. There was no change in blood glucose levels when individuals were in the fasted state (mean +/- SE, 8.1 +/- 0.2 vs. 8.1 +/- 0.1 mmol/L; before vs. after, respectively). However, blood glucose decreased by 28 +/- 1% at 0-1 h, by 33 +/- 1% at 1-2 h, by 35 +/- 1% at 2-3 h, by 38 +/- 2% at 3-4 h, by 43 +/- 2% at 4-5 h, and by 23 +/- 3% at 5-8 h (all P < 0.001). These results demonstrate that 1 h of ergocycle exercise has no clinical impact on blood glucose when performed in the fasted state in men with type 2 diabetes, whereas a significant decrease in blood glucose should be expected when the same exercise is performed postprandially.
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PMID:Impact of time interval from the last meal on glucose response to exercise in subjects with type 2 diabetes. 1094 94

Prescription of aerobic exercise for Type 2 diabetes mellitus (Type 2 DM) in clinical practice is frequently based on exercise intensity at maximum heart rate (60<HR(max)<79%), heart rate reserve (50<HR(reserve)<74%), and rating of perceived exertion (12<RPE<13). We examined these parameters in Japanese males with Type 2 DM at ventilatory threshold (VT) to investigate the exercise capacity of Type 2 DM patients and re-evaluate the exercise prescription. Fifty-six Japanese Type 2 DM males without autonomic neuropathy [age, 53.5+/-7.7 years; body mass index (BMI), 23.7+/-3.6 kg/m(2)] were enrolled and compared with 56 age- and BMI-matched healthy Japanese males. VT was determined breath by breath during exercise test using a ramp protocol and rates of oxygen consumption (VO(2)), work rate (WR), HR, DeltaHR, %HR(max), %HR(reserve), and RPE were measured at VT. Type 2 DM patients had significantly lower VO(2) (3.6+/-0.4 metabolic equivalents (METs)) and WR (62+/-14 W) than controls (VO(2), 3.9+/-0.6 METs; WR, 74+/-13 W). %HR(reserve), (32.6+/-7.7%) was also significantly lower compared with controls (37.6+/-8.3%), while %HR(max), was not different. RPE was also similar in diabetics (12.4+/-1.5) and controls (12.9+/-1.2), however, it was significantly lower in diabetic patients aged 60-69 years (11.8+/-2.0) and those with distal symmetric sensory neuropathy (12.2+/-1.0). Our results indicate reduced exercise capacity in Japanese Type 2 DM males and the exercise intensity of 60%HR(max), 30%HR(reserve), and RPE 12 is recommended in elderly diabetics and those with diabetic sensory neuropathy.
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PMID:Re-evaluation of exercise prescription for Japanese type 2 diabetic patients by ventilatory threshold. 1096 Jul 21

To determine whether uncoupling respiration from oxidative phosphorylation in skeletal muscle is a suitable treatment for obesity and type 2 diabetes, we generated transgenic mice expressing the mitochondrial uncoupling protein (Ucp) in skeletal muscle. Skeletal muscle oxygen consumption was 98% higher in Ucp-L mice (with low expression) and 246% higher in Ucp-H mice (with high expression) than in wild-type mice. Ucp mice fed a chow diet had the same food intake as wild-type mice, but weighed less and had lower levels of glucose and triglycerides and better glucose tolerance than did control mice. Ucp-L mice were resistant to obesity induced by two different high-fat diets. Ucp-L mice fed a high-fat diet had less adiposity, lower levels of glucose, insulin and cholesterol, and an increased metabolic rate at rest and with exercise. They were also more responsive to insulin, and had enhanced glucose transport in skeletal muscle in the setting of increased muscle triglyceride content. These data suggest that manipulating respiratory uncoupling in muscle is a viable treatment for obesity and its metabolic sequelae.
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PMID:Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice. 1101 31

Regular physical exercise has been known to be beneficial in the treatment of type 2 diabetes. Epidemiological studies of physical exercise: previous non-randomized studies suggested that a life-style intervention program involving diet and/or exercise reduced the progression of impaired glucose tolerance (IGT) to type 2 diabetes. Recent randomized controlled intervention trials also showed that diet and/or exercise intervention led to a significant decrease in the incidence of diabetes among those with IGT. Endocrinological and metabolic effects of exercise: in well controlled diabetic patients, physical exercise promotes utilization of blood glucose and lowers blood glucose levels. On the other hand, in poorly controlled diabetic patients with ketosis, physical exercise results in further rises in blood glucose, free fatty acids and ketone body concentrations. Long-term gentle regular jogging increases insulin action in respect of both carbohydrate and lipid metabolism despite no influence on body mass index or maximal oxygen uptake. A significant correlation was observed between deltaMCR (insulin sensitivity) and average daily steps Our recent data suggested that the improvement of insulin action by physical exercise was attributed, at least in part, to the increase in insulin-sensitive GLUT4 (glucose transporter 4) on the plasma membrane in skeletal muscle. In conclusion, as an adjunct to other forms of therapy, mild regular physical exercise will play an important role in primarily preventing type 2 diabetes.
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PMID:Diabetes and life-styles: role of physical exercise for primary prevention. 1124 67

Apoptosis is a physiological form of cell death that occurs during normal development, and critical mediators of this process include caspases, reactive oxygen species, and Ca2+. Excessive apoptosis of the pancreatic beta-cell has been associated with diabetes. Consequently, apoptosis research has focused on how infiltrating macrophages or cytotoxic T-cells might kill pancreatic beta-cells using cytokines or death receptor triggering. Meanwhile, the intracellular events in the target beta-cell have been largely ignored. Elucidation of such targets might help develop improved treatment strategies for diabetes. This article will outline recent developments in apoptosis research, with emphasis on mechanisms that may be relevant to beta-cell death in type 1 and type 2 diabetes. Several of the models proposed in beta-cell killing converge on Ca2+ signaling, indicating that the pancreatic beta-cell may be an ideal system in which to carefully dissect the role of Ca2+ during apoptosis.
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PMID:Role of apoptosis in pancreatic beta-cell death in diabetes. 1127

Pancreatic beta-cells are sensitive to a number of proapoptotic stimuli. Thus, apoptosis is an important part of the physiological neonatal remodeling of the endocrine pancreas, and a number of pathological stimuli involved in type 1 and type 2 diabetes have been shown to elicit beta-cell apoptosis. Factors of relevance to type 1 diabetes include proinflammatory cytokines, nitric oxide, and reactive oxygen species as well as Fas ligand. Recent findings that free fatty acids, glucose, sulfonylurea, and amylin cause beta-cell apoptosis in vitro suggest that programmed cell death may also be involved in the pathogenesis of type 2 diabetes. Furthermore, there is evidence favoring a convergence in signaling pathways toward common effectors of beta-cell apoptosis elicited by stimuli implicated in the pathogenesis of type 1 and type 2 diabetes. Therefore, recent studies involving the stimuli and signaling pathways of beta-cell apoptosis-in particular, mitogen- and stress-activated protein kinases-will be reviewed. It is concluded that immunological, inflammatory, and metabolic signals cause beta-cell apoptosis, and the possibility that these signals converge toward a common beta-cell death signaling pathway should be investigated further.
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PMID:beta-cell apoptosis: stimuli and signaling. 1127 4

The definable causes of nonalcoholic steatohepatitis (NASH) include jejunoileal bypass surgery (JIB), other causes of rapid and profound weight loss in obese subjects, total parenteral nutrition, drugs, industrial toxins, copper toxicity, and disorders characterized by extreme insulin resistance. However, the etiopathogenesis in most cases of NASH appears multifactorial. Obesity, type 2 diabetes, and hypertriglyceridemia are often associated with hepatic steatosis, and although this does not invariably lead to NASH, the fatty liver is vulnerable to hepatocellular injury initiated by reactive oxygen species (ROS). It is critical to understand not only the triggers for hepatitis (injury and inflammation) in NASH but also how this is perpetuated as chronic liver disease. The present focus is on whether the biochemical processes that generate oxidative stress lead to hepatocyte injury and secondary recruitment of inflammation or whether inflammation is the primary mediator of liver cell injury. Insulin resistance is a reproducible pathogenic factor in NASH. It favors accumulation of free fatty acids in the liver and predisposes to oxidative stress by stimulating microsomal lipid peroxidases and by the direct effects of high insulin levels in decreasing mitochondrial beta-oxidation. CYP2E1 is normally suppressed by insulin but is invariably increased in the livers of patients with NASH. In rodent dietary models of steatohepatitis, CYP2E1 is the catalyst of microsomal lipid peroxidation, while in Cyp 2e1 nullizygous mice, CYP4A proteins are induced and function as alternative microsomal lipid peroxidases. Other studies implicate activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) as leading to NASH; PPAR alpha is a transcription factor that governs both microsomal (via CYP4A) and peroxisomal (beta-oxidation) pathways of lipid oxidation and ultimately production of ROS. Increased lipid peroxidation is a crucial difference between the livers of rodents with experimental NASH and those of ob/ob genetically obese mice that have uncomplicated steatosis. Administration of endotoxin, through the release of tumor necrosis factor-alpha (TNF-alpha), provokes liver inflammation with hepatocyte injury in the steatotic liver. This may be particularly relevant in JIB and has been suggested as a pathogenic mechanism in primary NASH. It has been proposed that inheriting one or more copies of the hemochromatosis gene, C282Y, promotes fibrotic progression in NASH because of increased hepatic iron deposition, but recent studies have failed to confirm this. The relationship between the severity of hepatitis in NASH and progression to cirrhosis implies that products of the inflammatory infiltrate play a role in fibrogenesis. In summary, NASH can be regarded as the hepatic consequence of the metabolic syndrome (or syndrome X). Attention should now shift from steatosis, a generally benign process that is less evident in the advanced stages of cirrhosis, to the mechanisms for hepatocellular injury, inflammation, and hepatic fibrosis. In particular, the genetic, molecular, and cellular factors that ordain and moderate fibrosis in the context of steatohepatitis will be of greatest relevance to effective therapy and clinical outcome.
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PMID:Etiopathogenesis of nonalcoholic steatohepatitis. 1129 94

Oxidative ring opening of troglitazone (TGZ)(1) a thiazolidine 2,4-dione derivative used for the treatment of type II diabetes mellitus, leads to the formation of a quinone metabolite. The formation of TGZ quinone was shown to be NADPH dependent and to require active microsomal enzymes. Quinone formation was not affected by co-incubation with catalase or sodium azide and was partially inhibited (25%) by superoxide dismutase (SOD). Kinetic analysis of TGZ quinone formation in human liver microsomes implied single enzyme involvement. CYP3A isoforms were characterized as the primary enzymes involved in quinone formation by several lines of evidence including: (a) troleandomycin and ketoconazole almost completely inhibited microsomal quinone formation when SOD was present, whereas other CYP inhibitors had minimal effects (<20%); (b) TGZ quinone formation was highly correlated with regard to both contents (r(2): 0.9374) and activities (r(2): 0.7951) of CYP3A4 in human liver microsomes (HLM); (c) baculovirus insect cell-expressed human CYP3A4 was able to catalyze TGZ quinone formation at a higher capacity (V(max)/K(m)) than other human CYPs with the relative contribution of CYP3A4 in HLM estimated to be 20-fold higher than that of other CYPs; (d) TGZ quinone formation was increased by 350% in liver microsomes from rats pretreated with dexamethasone (DEX); and (e) plasma concentrations of TGZ quinone were increased by 260-680% in rats pretreated with DEX. The chemical nature of the quinone metabolite suggests an atypical CYP reaction consistent with a one-electron oxidation mechanism where an intermediate phenoxy radical combines with ferryl oxygen to subsequently form the quinone metabolite.
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PMID:Troglitazone quinone formation catalyzed by human and rat CYP3A: an atypical CYP oxidation reaction. 1138 77

It has been shown recently that troglitazone exerts an anti-inflammatory effect, in vitro, and in experimental animals. To test these properties in humans, we investigated the effect of troglitazone on the proinflammatory transcription factor nuclear factor-kappaB and its inhibitory protein IkappaB in mononuclear cells (MNC) and plasma soluble intracellular adhesion molecule-1, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and C-reactive protein. We also examined the effect of troglitazone on reactive oxygen species generation, p47(phox) subunit expression, 9-hydroxyoctadecadienoic acid (9-HODE), 13-HODE, o-tyrosine, and m-tyrosine in obese patients with type 2 diabetes. Seven obese patients with type 2 diabetes were treated with troglitazone (400 mg/day) for 4 weeks. Blood samples were obtained at weekly intervals. Nuclear factor-kappaB binding activity in MNC nuclear extracts was significantly inhibited after troglitazone treatment at week 1 and continued to be inhibited up to week 4. On the other hand, IkappaB protein levels increased significantly after troglitazone treatment at week 1, and this increase persisted throughout the study. Plasma monocyte chemoattractant protein-1 and soluble intracellular adhesion molecule-1 concentrations did not decrease significantly after troglitazone treatment, although there was a trend toward inhibition. Reactive oxygen species generation by polymorphonuclear cells and MNC, p47(phox) subunit protein quantities, plasminogen activator inhibitor-1, and C-reactive protein levels decreased significantly after troglitazone intake. 13-HODE/linoleic acid and 9-HODE/linoleic acid ratios also decreased after troglitazone intake. However, o-tyrosine/phenylalanine and m-tyrosine/phenylalanine ratios did not change significantly. These data show that troglitazone has profound antiinflammatory effects in addition to antioxidant effects in obese type 2 diabetics; these effects may be relevant to the recently described beneficial antiatherosclerotic effects of troglitazone at the vascular level.
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PMID:Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action? 1144 97

Elevation of glucose concentration in diabetes may induce generation of oxygen free radicals such as superoxide (O2*-) and hydroxyl (*OH). The aim of the present study was to investigate the effect of the oxidative stress on the activities of blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R) and aldose reductase, the levels of reduced glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances; TBARS) and plasma levels of insulin-like growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in type 2 (non-insulin-dependent diabetes) patients and in healthy controls. Blood SOD, CAT, GSH-Px and GSSG-R were lower in type 2 diabetic patients compared with the the control group. Blood aldose reductase activity was elevated in patients with type 2 diabetes compared with the control group. GSH was decreased while TBARS concentration was increased in red blood cells (RBC) and leukocytes from the patients with type 2 diabetes mellitus in comparison to the control group. The mean values of plasma LH, FSH and testosterone were decreased, whereas the mean plasma IGF-1 concentration was increased in type 2 diabetes compared with controls. These findings support the hypothesis that hyperglycemia enhances the activity of the polyol pathway and impairs the antioxidant status, particularly glutathione redox cycle, resulting in poorer defense against oxidative stress. In addition, decreased circulating testosterone and gonadotropin levels may reflect the oxidative stress exerted by diabetes.
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PMID:Oxidative stress and male IGF-1, gonadotropin and related hormones in diabetic patients. 1152 8


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