Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lactate and glycerol turnover is enhanced in obesity and NIDDM. To evaluate the influence of NIDDM on subcutaneous adipose tissue metabolism microdialysis combined with 133Xe clearance and measurements in arterialized plasma were carried out using samples of subcutaneous abdominal fat from nine obese NIDDM subjects (glucose, 7.9 +/- 0.7 mmol L-1) (mean +/- SEM) and nine obese non-diabetic subjects (glucose, 4.9 +/- 0.1) matched for age, BMI and body fat. After an overnight fast arterialized plasma levels were 1145 +/- 110 vs. 876 +/- 59 mumol L-1 (P < 0.05) for lactate and 75 +/- 10 vs. 66 +/- 8 mumol L-1 for glycerol in the diabetic and control group, respectively. The corresponding abdominal subcutaneous interstitial lactate and glycerol concentrations were 1278 +/- 63 vs 1107 +/- 64 mumol L-1 and 314 +/- 28 vs. 311 +/- 17 mumol L-1, respectively. However, adipose tissue blood flow in the same region was lower in NIDDM subjects (1.5 +/- 0.2 vs 2.4 +/- 0.3 mL 100 g-1 min-1) (P < 0.05). Consequently, apparent subcutaneous lactate and glycerol release, estimated according to Fick, were not statistically different in the two groups (1.8 +/- 0.4 vs 2.4 +/- 0.8 and 2.1 +/- 0.4 vs 3.1 +/- 0.5 mumol kg-1 min-1 in NIDDM and control subjects, respectively). Thus, in the post-absorptive state apparent lactate and glycerol release by the abdominal subcutaneous tissue in obese NIDDM subjects was similar to that in a matched group of obese non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Microdialysis assessment of adipose tissue metabolism in post-absorptive obese NIDDM subjects. 758 14

Recent evidence suggests that expression of tumor necrosis factor-alpha (TNF-alpha) by adipocytes is a molecular mediator of insulin resistance in obesity. We have therefore tested the hypothesis that variations within the regulatory region of the TNF-alpha gene, which might cause increased adipocyte or generalized TNF-alpha synthesis, are associated with NIDDM, a state in which insulin resistance is routinely observed. Neither the previously known variants within the TNF-alpha promoter at position -308 and -238, nor two newly identified polymorphisms at position -376 and -163, were found at a significantly higher frequency in Caucasian NIDDM patients compared to non-diabetic controls. No genetic variants were found in Pima Indians. These data make it unlikely that mutations within regulatory elements of the TNF-alpha gene are associated with an increase in the prevalence of NIDDM.
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PMID:Genetic variability in the TNF-alpha promoter is not associated with type II diabetes mellitus (NIDDM). 759 12

Many models of diabetes dyslipidemia are available. Animals with chemically-induced diabetes have been used to study insulin-dependent diabetes. Hypercholesterolemia in streptozotocin-induced diabetes in rats results from increased intestinal absorption and synthesis of cholesterol. Lipoproteins from diabetic rats are oxidized and demonstrate cytotoxicity, a feature which can be prevented by insulin or antioxidant treatment. Diabetic rabbits fed a cholesterol-rich diet do not develop atherosclerotic lesions because accumulated VLDL are apo E-depleted, too large and do not enter into the arterial wall. Models for non-insulin-dependent diabetes (NIDDM) are obtained through selective breeding or dietary conditions. The obese Zucker rat (fa/fa) is characterized by hyperphagy, hyperglycaemia, hyperinsulinemia, insulin-resistance, hypertriglyceridemia and hypercholesteolemia. It responds to dietary, hormonal and drug treatments, but does not develop atherosclerosis spontaneously. It is used as a model for obesity, NIDDM and type IV hyperlipidemia. The JCR:LA cp rat bears the corpulent gene and develops similar characteristics to those of the Zucker rat. However, insulin-resistance is more severe in homozygous males (cp/cp), and cardiovascular lesions are observed. Their appearance is reduced by treatments which decrease hyperinsulinemia and insulin resistance but not by lowering lipid levels alone. The sand rats (Psammomys obesus) develop obesity and NIDDM when fed a laboratory diet. When cholesterol and anti-thyroid drug are added to the diet, they develop cardiovascular lesions. This species constitutes a new model for studying atherosclerosis-related diabetes.
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PMID:Dyslipidemia and diabetes: animal models. 762 69

Effects of 12 months of simvastatin treatment were examined in 48 NIDDM patients with total serum cholesterol levels exceeding 220 mg/dl and were compared with those in 35 nondiabetic patients with hypercholesterolemia. In the diabetic group, 5-10 mg of simvastatin given once daily at bedtime significantly lowered total cholesterol (21%). LDL cholesterol (28%), apoB (15%) and triglycerides (8%) levels. These changes were identical to those in the nondiabetic group, except for triglycerides which did not change significantly. HDL cholesterol increased significantly in the nondiabetic group but not in the diabetic group. The reductions in LDL cholesterol and apoB in hypercholesterolemic patients with NIDDM were not influenced by gender, age, glycemic control, the presence or absence of systemic hypertension, obesity and overt proteinuria. In addition, the decrease in LDL cholesterol was not affected by the number of risk factors per patient. Simvastatin did not significantly alter hemoglobin A1c or fasting plasma glucose and was well tolerated in both groups. Simvastatin produced beneficial effects on serum lipids and apolipoproteins and neutral effects on glycemic control in hypercholesterolemic patients with NIDDM, whether or not they had an additional atherosclerotic risk factor.
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PMID:Long-term effects of simvastatin in hypercholesterolemic patients with NIDDM and additional atherosclerotic risk factors. Hyogo Simvastatin Study Group. 764 76

Four group of age- and sex-matched patients were studied: 1. nondiabetic subjects (n = 20) with a body mass index (BMI) < 25 Kg/m2 (lean control subjects); 2. obese non diabetic subjects (n = 22) with a BMI > 30 Kg/m2 (obese control subjects); 3. lean NIDDM subjects (n = 22); and 4. obese NIDDM subjects (n = 24). We determined: total cholesterol, triglycerides, HDL-cholesterol, blood glucose, Apolipoproteins A1 and B, insulin, Lp(a), Factor VII, fibrinogen, plasminogen, t-PA(Ag) pre and post venous occlusion (VO) and PAI activity pre and post VO. In addition to metabolic abnormalities obese non diabetic subjects and lean and obese NIDDM patients displayed significantly higher levels of fibrinogen, Factor VII, plasminogen, PAI pre and post VO and tPA(Ag) pre VO and significantly lower levels of t-PA(Ag) post VO. Our findings demonstrate an impairment of the haemostatic and fibrinolytic mechanisms which may be a key role in the pathogenesis of atherosclerotic vascular complications in obesity and in NIDDM.
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PMID:Blood coagulation and fibrinolysis in obese NIDDM patients. 764 83

The C57BL/6J mouse develops obesity and diabetes in response to a high-fat, high-simple carbohydrate diet. To determine the dynamics of glucose-induced insulin release in this animal model of NIDDM, we studied the acute insulin response to glucose of perifused islets in C57BL/6J (diabetes-prone) and A/J (diabetes-resistant) mice fed a normal control diet and of others fed a diabetogenic diet. The insulin response of normal C57BL/6J islets was almost monophasic, with a deficiency in the second phase during high glucose stimulation when compared to that of A/J control islets. The defect in C57BL/6J mice was exaggerated in animals fed a diabetogenic diet. It is suggested that a latent deficiency of second phase insulin release may contribute to the development of the diet-induced syndrome in this model.
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PMID:Impaired second phase insulin response of diabetes-prone C57BL/6J mouse islets. 765 47

From pluripotent pancreatic rat islet tumor tissue we have previously reported the isolation of stable transplantable glucagonoma tumor phenotypes in rats characterized by acute onset of anorexia. We now report that these tumors also cause severe adipsia. Food and water intake is reduced by more than 95% and is immediately cured upon tumor removal. Four anorectic tumor lines were all characterized as glucagonomas with high levels of proglucagon mRNA, and of two tested both were associated with highly elevated plasma levels of glucagon as well as of Glp-1(7-36amide) in the host rat. This fetal processing pattern of proglucagon may be indirectly linked to the anorectic phenotype, since we have now isolated a non-anorectic glucagonoma with similar levels of proglucagon mRNA. Lack of anorexia/adipsia in SV-40-T-antigen driven glucagonomas in transgenic mice with similar fetal processing as reported by other suggests that our tumors produce a novel anorectic substance. This factor ranges among the most potent of its kind as a peripheral mediator involved in appetite and thirst regulation. In summary, the glucagonomas provide an interesting tool with which to study the nature of severe anorexia as well as adipsia, and the identification of the active substance(s) may provide novel therapeutics for the treatment of obesity-related disorders such as NIDDM.
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PMID:Transplantable glucagonomas derived from pluripotent rat islet tumor tissue cause severe anorexia and adipsia. 765 79

Nuclear families of non-insulin-dependent diabetic (NIDDM) patients are uncommon, as usually one or both parents have died. In order to aid identification of complete nuclear families, we have ascertained the disease process at a younger age by studying subjects with previous gestational diabetes. One hundred women who had had gestational diabetes, age (+/- SD) 38 (6) years, were screened by fasting plasma glucose (fpg). Sixty-one were found to have either fasting hyperglycaemia (5.5 < or = fpg < 7.8 mmol/l) or diabetes. Of these women 35 had both parents alive and the parents of 14 of these women agreed to the assessment of their metabolism by a continuous infusion of glucose with model assessment (CIGMA). Seven probands had impaired glucose tolerance (IGT) and seven were diabetic. They were age 35 (4) years and had body mass index (BMI) 26 (5) kg/m2. The parents were aged 62 (6) years and had BMI 29 (6) kg/m2 and their affection status was defined as presence of glucose intolerance (fpg or post-infusion achieved plasma glucose level > 2 SD of an age and obesity matched population). In the 14 families, five probands (36%) had neither parent affected, six (43%) had one parent affected and three (21%) had both parents affected. Only three probands had a parent with diabetes as defined by World Health Organisation criteria. We conclude that the study of women who have had gestational diabetes allows detection of probands with diabetes or impared glucose tolerance, who have both parents available for study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes. 767 91

The insulin receptor is expressed as two isoforms that differ by a 12-amino acid region at the carboxy-terminus of the alpha-subunit encoded by exon 11. These isoforms are produced by tissue-specific alternate splicing of the insulin receptor mRNA. To determine whether the relative expression of the isoforms is altered in skeletal muscle in two insulin-resistant states, NIDDM and obesity, relative mRNA levels were measured using a polymerase chain reaction technique. There were no differences in the relative amounts of skeletal muscle mRNA encoding the exon 11-containing form compared to the exon 11-lacking form of the insulin receptor among lean normal (30 +/- 2% Ex11-), obese nondiabetic (32 +/- 2%), and NIDDM (31 +/- 1%) subjects. We conclude that altered expression of insulin receptor isoform mRNAs does not account for skeletal muscle insulin resistance in NIDDM and obesity.
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PMID:Relative expression of insulin receptor isoforms does not differ in lean, obese, and noninsulin-dependent diabetes mellitus subjects. 768 96

Quite different nutrition-related environmental factors influence the development of type 1 insulin-dependent diabetes (IDDM) and type 2 non-insulin-dependent diabetes (NIDDM). IDDM is characterized by progressive beta-cell destruction which leads to complete insulin deficiency; at the time of diagnosis 80-90% of beta cells have been destroyed. In children there is epidemiological evidence that high intake of nitrites and N-nitroso compounds, early introduction of cow's milk to the diet and short duration or absence of breastfeeding increase the risk of IDDM. Studies in experimental animals suggest that cow's milk and soy proteins may be diabetogenic. There is current interest in the effects of free radical scavengers, particularly niacin and natural and synthetic antioxidants on the incidence of IDDM. These findings from ecological, animal, and human case-control studies remain to be evaluated in prospective cohort studies covering infancy and childhood and finally in human intervention trials. NIDDM is characterized by insulin resistance which is complicated by impaired insulin secretion at the time of appearance of hyperglycaemia and clinical diabetes. Its preclinical development is insidious and poorly defined, and there is little direct evidence that the same factors which influence metabolic control in clinical diabetes also affect the preclinical development of the disorder. Obesity, particularly of the abdominal type, is common in people who develop NIDDM, and weight control by appropriate diet and physical activity is probably the most important measure for preventing NIDDM. High (saturated) fat intake seems to be associated with insulin resistance, obesity and increased risk of NIDDM, and diets high in carbohydrate seem to protect from glucose intolerance and diabetes, mainly owing to their high fibre content.
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PMID:Dietary factors in the aetiology of diabetes. 769 75


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