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)

Type 2 diabetes mellitus has become an epidemic, and virtually no physician is without patients who have the disease. Whereas insulin insensitivity is an early phenomenon partly related to obesity, pancreas beta-cell function declines gradually over time already before the onset of clinical hyperglycaemia. Several mechanisms have been proposed, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction for insulin resistance, and glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction. Moreover, the disease has a strong genetic component, but only a handful of genes have been identified so far: genes for calpain 10, potassium inward-rectifier 6.2, peroxisome proliferator-activated receptor gamma, insulin receptor substrate-1, and others. Management includes not only diet and exercise, but also combinations of anti-hyperglycaemic drug treatment with lipid-lowering, antihypertensive, and anti platelet therapy.
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PMID:Type 2 diabetes: principles of pathogenesis and therapy. 1582 85

Evidence for a genetic basis for type 2 diabetes and the metabolic syndrome has been derived from studies of families, twins and populations with genetic admixture. Identification of genes associated with disease pathogenesis is now underway using techniques such as genome scanning by positional cloning and the candidate gene approach. Genome scanning in several different ethnic groups has identified chromosome regions harbouring type 2 diabetes susceptibility genes such as the novel gene, calpain 10 (CAPN10). The hepatic nuclear factor 4alpha (HNF4alpha) gene partly explains the linkage peak on chromosome 20, while the upstream transcription factor (USF1) is associated with familial combined hyperlipidaemia (FCHL) and maps close to the type 2 diabetes associated 1q peak. Peroxisome proliferator-activated receptor gamma (PPARgamma) was identified as a candidate gene based on its biology. A Pro12Ala variant of this gene has been associated with an increased risk of type 2 diabetes. Many genes accounting for monogenic forms of diabetes have been identified--such as maturity onset diabetes of the young (MODY); glucokinase (GCK) and HNF1alpha mutations being the most common causes of MODY. GCK variants result in 'mild' diabetes or impaired glucose tolerance (IGT) and relatively few cardiovascular complications, while HNF1alpha-associated MODY is more typical of type 2 diabetes, frequently being treated with sulphonylureas or insulin and resulting in microvascular complications. Testing for single gene disorders associated with type 2 diabetes and obesity may determine cause, prognosis and appropriate treatment; however, for the more common polygenic diseases this is not the case. In type 2 diabetes, molecular genetics has the potential to enhance understanding of disease pathogenesis, and help formulate preventative and treatment strategies.
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PMID:Searching for genes in diabetes and the metabolic syndrome. 1603 91

Type 2 diabetes mellitus (T2DM) can lead to death without treatment and it has been predicted that the condition will affect 215 million people worldwide by 2010. T2DM is a multifactorial disorder whose precise genetic causes and biochemical defects have not been fully elucidated, but at both levels, calpains appear to play a role. Positional cloning studies mapped T2DM susceptibility to CAPN10, the gene encoding the intracellular cysteine protease, calpain 10. Further studies have shown a number of noncoding polymorphisms in CAPN10 to be functionally associated with T2DM while the identification of coding polymorphisms, suggested that mutant calpain 10 proteins may also contribute to the disease. Here we review recent studies, which in addition to the latter enzyme, have linked calpain 5, calpain 3, and its splice variants, calpain 2 and calpain 1 to T2DM-related metabolic pathways along with T2DM-associated phenotypes, such as obesity and impaired insulin secretion, and T2DM-related complications, such as epithelial dysfunction and diabetic cataract.
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PMID:Calpains and their multiple roles in diabetes mellitus. 1715 22

Exercise training plays a major role in the improving physiology of diabetes. Herein we aimed to investigate the influence of exercise upon the calcium-dependent calpain-isoform expressions of lean or obese Zucker rats, a model of obesity and type II diabetes (NIDDM). Five-month-old rats were divided: (1) obese sedentary (OS, n=7); (2) obese exercise (OE, n=7); (3) lean sedentary (LS, n=7); (4) lean exercise (LE, n=7). After 2-month exercise (treadmill running), the body weight (BW) and expression of calpain 10, mu-calpain, and m-calpain in skeletal muscles were determined by RT-PCR, using beta-actin as internal standard. We found exercise is useful for BW lossing, especially in the obese rats. The BW difference between OS and OE rats (69 g vs. 18.2 g) was more significantly than that between LS and LE rats (41.8 g vs. 28.7 g). The calpain 10 expression of LS rats (0.965) was lower than that of LE rats (1.006), whereas those of OS and OE were comparable. The mu- or m-calpain expressions of sedentary groups (OS, LS) was significantly higher than those of exercise groups (OE, LE). The mu-calpain expression (1.13/0.92) and m-calpain expression (1.01/0.99) of OS/LS rats was significantly higher than those of OE/LE rats [1.07/0.9 (micro-calpain); 0.97/0.95 (m-calpain)]. We concluded that the micro- or m-calpains in skeletal muscle are regulated by exercise in both lean and obese Zucker rats. Exercise and BW controlling might improve the physiopathology of obesity and diabetes. Both micro- or m-calpains might become useful markers for prognoses of diabetes.
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PMID:Effect of exercise training on calpain systems in lean and obese Zucker rats. 1880 75