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The circulating level of the inflammatory cytokine interleukin (IL)-6 is elevated in various insulin-resistant states including type 2 diabetes, obesity, cancer, and HIV-associated lipodystrophy. To determine the role of IL-6 in the development of insulin resistance, we examined the effects of IL-6 treatment on whole-body insulin action and glucose(More)
Obese, insulin-resistant states are characterized by a paradoxical pathogenic condition in which the liver appears to be selectively insulin resistant. Specifically, insulin fails to suppress glucose production, yet successfully stimulates de novo lipogenesis. The mechanisms underlying this dysregulation remain controversial. Here, we hypothesized that(More)
To investigate the physiological effects of modulating the abundance of Munc18c or syntaxin 4 (Syn4) proteins on the regulation of glucose homeostasis in vivo, we generated tetracycline-repressible transgenic mice that overexpress either Munc18c or Syn4 proteins in skeletal muscle, pancreas and adipose tissue seven-, five-, and threefold over endogenous(More)
Uncoupling protein 1 (UCP1) is highly expressed in brown adipose tissue, where it generates heat by uncoupling electron transport from ATP production. UCP1 is also found outside classical brown adipose tissue depots, in adipocytes that are termed 'brite' (brown-in-white) or 'beige'. In humans, the presence of brite or beige (brite/beige) adipocytes is(More)
Low or absent expression of the cyclin-dependent kinase inhibitor p27(Kip1) serves as an excellent malignant marker for prostate and other human cancers. The level of p27(Kip1) is regulated primarily by the ubiquitin E3 ligase SCF(SKP2) through ubiquitin-dependent proteolysis. Expression of the F-box protein SKP2 is inversely correlated with p27 in many(More)
Glutamic acid decarboxylase (GAD) is one major autoantigen involved in the pathogenesis of autoimmune insulin dependent diabetes mellitus (IDDM). Molecular mechanisms regulating GAD expression in pancreatic beta cell are still ill-defined. Here we investigated the effect of streptozotocin (STZ), a beta cell-specific toxin, on the expression of GAD67 in(More)
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is central to the action of insulin and many growth factors. Heterozygous mutations in the gene encoding the p85α regulatory subunit of PI3K (PIK3R1) have been identified in patients with SHORT syndrome - a disorder characterized by short stature, partial lipodystrophy, and insulin resistance. Here,(More)
Low or absent expression of the cyclin-dependent kinase inhibitor p27 serves as an excellent malignant marker for prostate and other human cancers. The level of p27 is regulated primarily by the ubiquitin E3 ligase SCF through ubiquitin-dependent proteolysis. Expression of the F-box protein SKP2 is inversely correlated with p27 in many cancers. To determine(More)
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