Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0311277 (abdominal obesity)
 2,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity, the metabolic syndrome, and type 2 diabetes mellitus (T2DM) are major global health problems. Insulin resistance is frequently present in these disorders, but the causes and effects of such resistance are unknown. Here, we generated mice with muscle-specific knockout of the major murine atypical PKC (aPKC), PKC-lambda, a postulated mediator for insulin-stimulated glucose transport. Glucose transport and translocation of glucose transporter 4 (GLUT4) to the plasma membrane were diminished in muscles of both homozygous and heterozygous PKC-lambda knockout mice and were accompanied by systemic insulin resistance; impaired glucose tolerance or diabetes; islet beta cell hyperplasia; abdominal adiposity; hepatosteatosis; elevated serum triglycerides, FFAs, and LDL-cholesterol; and diminished HDL-cholesterol. In contrast to the defective activation of muscle aPKC, insulin signaling and actions were intact in muscle, liver, and adipocytes. These findings demonstrate the importance of aPKC in insulin-stimulated glucose transport in muscles of intact mice and show that insulin resistance and resultant hyperinsulinemia owing to a specific defect in muscle aPKC is sufficient to induce abdominal obesity and other lipid abnormalities of the metabolic syndrome and T2DM. These findings are particularly relevant because humans who have obesity, impaired glucose tolerance, and T2DM reportedly have defective activation and/or diminished levels of muscle aPKC.
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PMID:Muscle-specific knockout of PKC-lambda impairs glucose transport and induces metabolic and diabetic syndromes. 1764 77

Insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) expression may provide an indirect reflection of the capacity of adipocytes to respond to insulin stimulation. We examined messenger RNA (mRNA) expression of these genes in omental and subcutaneous adipose tissue of women. Paired omental and subcutaneous adipose tissue samples were obtained from 36 women (age, 47 +/- 5 years; body mass index, 28.0 +/- 5.4 kg/m(2)) undergoing gynecologic surgeries. Total adiposity and visceral adiposity were assessed by dual-energy x-ray absorptiometry and computed tomography. The GLUT4 and IRS-1 mRNA expression levels were both significantly higher in subcutaneous compared with omental adipose tissue. A negative correlation was observed between body fat percentage and subcutaneous adipose tissue GLUT4 (r = -0.39, P < .05) and IRS-1 (r = -0.30, P < .08) mRNA abundance. However, in omental fat, only GLUT4 mRNA was inversely associated with body fat percentage (r = -0.53, P < .001). Moreover, the homeostasis model assessment of insulin resistance index was associated with mRNA expression of subcutaneous GLUT4 (r = -0.56, P < .001), subcutaneous IRS-1 (r = -0.51, P < .01), and omental GLUT4 (r = -0.54, P < .001), but not omental IRS-1. Interestingly, plasma adiponectin was only associated with subcutaneous GLUT4 (r = 0.48, P < .01) and IRS-1 (r = 0.48, P < .05) mRNA expression. The GLUT4 protein, unlike mRNA expression, was higher in omental than in subcutaneous adipose tissue. However, abdominal obesity-related differences in protein or mRNA expression were similar. Omental IRS-1 expression was low and unaffected by visceral obesity. In contrast, omental and subcutaneous GLUT4 as well as subcutaneous IRS-1 were reduced in visceral obesity. This divergent pattern of expression may reflect a lower capacity of omental adipose tissue to respond to insulin stimulation at all adiposity levels.
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PMID:Glucose transporter 4 and insulin receptor substrate-1 messenger RNA expression in omental and subcutaneous adipose tissue in women. 1937 84