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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.
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PMID:Endothelial dysfunction and type 2 diabetes. Part 1: physiology and methods for exploring the endothelial function. 1154 16

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.
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PMID:Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus. 1154 17

To examine whether and how intramyocellular lipid (IMCL) content contributes to interindividual variation in insulin action, we studied 20 healthy men with no family history of type 2 diabetes. IMCL was measured as the resonance of intramyocellular CH(2) protons in lipids/resonance of CH(3) protons of total creatine (IMCL/Cr(T)), using proton magnetic resonance spectroscopy in vastus lateralis muscle. Whole-body insulin sensitivity was measured using a 120-min euglycemic-hyperinsulinemic (insulin infusion rate 40 mU/m(2). min) clamp. Muscle biopsies of the vastus lateralis muscle were taken before and 30 min after initiation of the insulin infusion to assess insulin signaling. The subjects were divided into groups with high IMCL (HiIMCL; 9.5 +/- 0.9 IMCL/Cr(T), n = 10) and low IMCL (LoIMCL; 3.0 +/- 0.5 IMCL/Cr(T), n = 10), the cut point being median IMCL (6.1 IMCL/Cr(T)). The groups were comparable with respect to age (43 +/- 3 vs. 40 +/- 3 years, NS, HiIMCL versus LoIMCL), BMI (26 +/- 1 vs. 26 +/- 1 kg/m(2), NS), and maximal oxygen consumption (33 +/- 2 vs. 36 +/- 3 ml. kg(-1). min(-1), NS). Whole-body insulin-stimulated glucose uptake was lower in the HiIMCL group (3.0 +/- 0.4 mg. kg(-1). min(-1)) than the LoIMCL group (5.1 +/- 0.5 mg. kg(-1). min(-1), P < 0.05). Serum free fatty acid concentrations were comparable basally, but during hyperinsulinemia, they were 35% higher in the HiIMCL group than the LoIMCL group (P < 0.01). Study of insulin signaling indicated that insulin-induced tyrosine phosphorylation of the insulin receptor (IR) was blunted in HiIMCL compared with LoIMCL (57 vs. 142% above basal, P < 0.05), while protein expression of the IR was unaltered. IR substrate-1-associated phosphatidylinositol (PI) 3-kinase activation by insulin was also lower in the HiIMCL group than in the LoIMCL group (49 +/- 23 vs. 84 +/- 27% above basal, P < 0.05 between HiIMCL and LoIMCL). In conclusion, IMCL accumulation is associated with whole-body insulin resistance and with defective insulin signaling in skeletal muscle independent of body weight and physical fitness.
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PMID:Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle. 1157 17

To evaluate the effect of exercise training on serum leptin levels 50 sedentary subjects with type 2 diabetes were enrolled in either 6 weeks of aerobic exercise training with diet therapy (n = 23) or diet therapy alone (n = 27). The training program consisted of walking and cycle ergometer exercise for 1 hour at least 5 times per week, with the intensity of exercise maintained at 50% of maximum oxygen uptake. Serum leptin levels decreased significantly in the exercise training (TR) group (7.2 +/- 3.6 to 4.6 +/- 2.5 ng/mL, P <.05), but not in the sedentary (SED) group (6.9 +/- 3.4 to 5.6 +/- 2.9 ng/mL). Leptin levels standardized for percentage body fat (dividing serum leptin level by percentage body fat) after treatment were lower in the TR subjects compared with the SED subjects. Body weight and percentage body fat decreased in all patients; however, no significant changes were observed in either group. Fasting concentrations of plasma insulin and cortisol and the urinary excretion of 17-hydroxycorticosteroid (17-OHCS) did not differ between the groups either before or after treatment. Fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) improved significantly in both groups, although no significant differences were observed between the groups either before or after treatment. Ventilatory threshold increased significantly in the exercise training subjects. This study demonstrates that exercise training in type 2 diabetic subjects reduces serum leptin levels independent of changes in body fat mass, insulin, or glucocorticoids.
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PMID:Effect of exercise training on serum leptin levels in type 2 diabetic patients. 1158 83

The cytotoxic side effects of anti-neoplastic drugs are increased in patients with either type 1 or type 2 diabetes mellitus by a mechanism that is not clearly defined. We report that the circulating glucose metabolite, methylglyoxal (MGO), enhances cisplatin-induced apoptosis by activating protein kinase Cdelta (PKCdelta). We found that treatment of myeloma cells with the antioxidant N-acetylcysteine completely blocked cisplatin-dependent intracellular GSH oxidation, reactive oxygen species (ROS) generation, poly(ADP-ribose) polymerase cleavage, and apoptosis. Importantly, co-treatment of cells with the reactive carbonyl MGO and cisplatin increased apoptosis by 90% over the expected additive effect of combined MGO and cisplatin treatment. This same synergism was also observed when ROS generation was examined. MGO and cisplatin increased PKCdelta activity by 4-fold, and this effect was blocked by the PKCdelta inhibitor rottlerin but not by NAC. Furthermore, rottlerin blocked combined MGO and cisplatin-induced ROS generation and apoptosis. Finally, MGO and cisplatin induced c-Abl activation and c-Abl:PKCdelta association. Rottlerin blocked c-Abl activation, but the c-Abl inhibitor STI-571 increased MGO and cisplatin-induced apoptosis by 50%. Taken together these data indicate that MGO synergistically enhances cisplatin-induced apoptosis through activation of PKCdelta and that PKCdelta is critical to both cell death and cell survival pathways. These findings suggest that in the patient with diabetes mellitus heightened oxidative stress can enhance the cytotoxicity of agents that induce DNA damage.
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PMID:Methylglyoxal enhances cisplatin-induced cytotoxicity by activating protein kinase Cdelta. 1170 30

To gain insight into the pathogenesis of diabetic cardiomyopathy, we investigated cardiac function in terms of the coupling of left ventricular mechanical work and the energetics in Otsuka Long-Evans Tokushima Fatty rats, which are well known as a model of type 2 diabetes mellitus (DM). Neither left ventricular systolic function and mean coronary flow nor coronary flow reserve differed even in late DM rats. The amount of oxygen required for mechanical work and contraction was unaltered, although myosin isozyme was finally transformed from V(1) to V(3). The maximum pacing rate was decreased from 300 to 240 beats/min, and the left ventricular relaxation rate was significantly (P < 0.05) slower only in late DM rats, resulting in decreased oxygen consumption per minute for total Ca(2+) handling in excitation-contraction coupling mainly consumed by sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) without significant changes in basal metabolism or in mitochondrial oxidative phosphorylation. The protein level of SERCA2 in membranes was significantly (P < 0.001) lower in severe DM rats. We conclude that the only lusitropic dysfunction due to the depressed expression of SERCA2 is related to generating diabetic cardiomyopathy even in the present type 2 diabetic rats.
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PMID:Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats. 1174 57

Three zinc(II) complexes of picolinic acid and its derivatives with a Zn(N2O2) coordination mode were prepared and evaluated for their insulinomimetic activities by in vitro and in vivo studies. By introducing an electron-donating methyl group into the picolinate ligand (pic), bis(6- or 3-methylpicolinato)zinc(II) complexes [Zn(6-mpa)2 or Zn(3-mpa)2, respectively] were prepared. The Zn(6-mpa)(2) complex was crystallized as a water adduct [Zn(6-mpa)2(H2O)].H2O, in which two carboxylate oxygens and two pyridine nitrogens of 6-mpa and a water oxygen coordinate to a zinc(II) with a trigonal bipyramidal geometry. By in vitro evaluation of the inhibition of free fatty acid (FFA) release from isolated rat adipocytes in the presence of epinephrine, the insulinomimetic activities of Zn(pic)2, Zn(6-mpa)2, and Zn(3-mpa)2 (IC50=0.64 +/- 0.13, 0.31 +/- 0.05, and 0.40 +/- 0.07 mM, respectively) were found to be higher than those of VOSO(4) (IC50=1.00 mM) and ZnSO(4) (IC50=1.58 +/- 0.05 mM) in terms of IC50 value, the 50% inhibition concentrations for the FFA release from the adipocytes. Then, Zn(6-mpa)2, which exhibited the highest in vitro insulinomimetic activity among three complexes examined, was given at a dose of 3.0 mg (45.9 micromol) Zn/kg body weight to KK-A(y) mice with type 2 diabetes mellitus by daily intraperitoneal injections for 14 days and it was found that the hereditary high blood glucose levels were lowered during the administration of the complex. The improvement of diabetes mellitus was confirmed with the oral glucose tolerance test.
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PMID:Development of new insulinomimetic zinc(II) picolinate complexes with a Zn(N2O2) coordination mode: structure characterization, in vitro, and in vivo studies. 1186 42

We investigated the effect of an 8 week circuit training (CT) program, combining aerobic and resistance exercise, on indices of glycemic control, cardiorespiratory fitness, muscular strength and body composition in 16 subjects (age 52 +/- 2 years) with type 2 diabetes using a prospective randomised crossover protocol. Submaximal exercise heart rate and rate pressure product were significantly lower after training (P<0.05), whilst ventilatory threshold increased (11.8 +/- 0.7 vs 13.8 +/- 0.6 ml kg(-1)min(-1), P<0.001). Muscular strength also increased with training (403 +/- 30 to 456 +/- 31 kg, P<0.001), whilst skinfolds (148.7 +/- 11.5 vs 141.1 +/- 10.7 mm, P<0.05), % body fat (29.5 +/- 1.0 vs 28.7 +/- 1.1%, P<0.05) and waist:hip ratio (99.2 +/- 1.5 vs 97.9 +/- 1.4%, P<0.05) significantly decreased. Concurrently, peak oxygen uptake (P<0.05) and exercise test duration (P<0.001) increased following training, whilst glycated hemoglobin (P<0.05) and fasting blood glucose (P<0.05) decreased. CT is an effective method of training that improved functional capacity, lean body mass, strength and glycemic control in subjects with type 2 diabetes.
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PMID:Combined aerobic and resistance exercise improves glycemic control and fitness in type 2 diabetes. 1189 Oct 19

The ORP150 gene that encodes the human oxygen-regulated protein (150 kDa) maps to chromosome 11q23, a region previously reported to be linked to type 2 diabetes and obesity in Pima Indians. This gene was also found to be differentially expressed in global gene expression studies comparing muscle mRNA from insulin-resistant versus insulin-sensitive subjects. Therefore, ORP150 was analyzed as a candidate gene for susceptibility to diabetes. Twelve variants were identified, and three unique representative polymorphisms were genotyped in 1,338 Pima Indians. None of these polymorphisms were associated with diabetes, but two polymorphisms were significantly associated with measures of insulin resistance. These data indicate that ORP150 has a role in insulin action but does not have a major role in determining susceptibility to type 2 diabetes in Pima Indians.
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PMID:Polymorphisms in the oxygen-regulated protein 150 gene (ORP150) are associated with insulin resistance in Pima Indians. 1197 64

Oxidative stress is induced under diabetic conditions and causes various forms of tissue damage in patients with diabetes. Recently, pancreatic beta-cells have emerged as a putative target of oxidative stress-induced tissue damage and this seems to explain in part the progressive deterioration of beta-cell function in type 2 diabetes. As a step toward clinical trial of antioxidant for type 2 diabetes, we investigated the possible anti-diabetic effects of probucol, an antioxidant widely used as an anti-hyperlipidemic agent, on preservation of beta-cell function in diabetic C57BL/KsJ-db/db mice. Probucol-containing diet was given to mice from 6 to 16 weeks of age. Immunostaining for oxidative stress markers such as 4-hydroxy-2-nonenal (HNE)-modified proteins and heme oxygenase-1 revealed that probucol treatment decreased reactive oxygen species (ROS) in pancreatic islets of diabetic animals. Oxidative stress is known to enhance apoptosis of beta-cells and to suppress insulin biosynthesis, but probucol treatment led to preservation of beta-cell mass and the insulin content. According to intraperitoneal glucose tolerance tests, the probucol treatment preserved glucose-stimulated insulin secretion and improved glucose tolerance at 10 and 16 weeks: insulin, 280+/-82 vs. 914+/-238 pmol/l (120 min, at 16 weeks; P<0.05); glucose, 44.6+/-2.4 vs. 35.2+/-2.6 mmol/l (120 min, at 16 weeks; P<0.05). Thus, our present observations demonstrate the potential usefulness of probucol for treatment of type 2 diabetes.
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PMID:Probucol preserves pancreatic beta-cell function through reduction of oxidative stress in type 2 diabetes. 1200 24


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