IRS-1 (Phospho-Ser1101) ELISA Kit

OBJECTIVE: Phosphorylation of insulin receptor substrate (IRS) 1 by tumor necrosis factor alpha (TNF-alpha) has been implicated as a factor contributing to insulin resistance. Administration of IL-15 reduces adipose tissue deposition in young rats and stimulates secretion of adiponectin, an insulin sensitizing hormone that inhibits the production and activity of TNF-alpha. We aimed at investigating the effects of age life-long moderate calorie restriction (CR) on IL-15 and TNF-alpha signaling in rat white adipose tissue (WAT). MATERIALS AND METHODS: Thirty-six 8-month-old, 18-month-old, and 29-month-old male Fischer344'Brown Norway F1 rats (6 per group) were either fed ad libitum (AL) or calorie restricted by 40%. The serum levels of IL-15 and IL-15 receptor alpha-chain (IL-15R alpha) were increased by CR controls regardless of age. An opposite pattern was detected in WAT. In addition, CR reduced gene expression of TNF-alpha and cytosolic IRS1 serine phosphorylation in WAT, independently from age. RESULTS: IL-15 signaling in WAT is increased over the course of aging in AL rats compared with CR rodents. Protein levels of IL-16Ra are greater in WAT of AL than in CR rats independently from age. This adaptation was paralleled by increased IRS1 phosphorylation through TNF-alpha-mediated insulin resistance. Adiponectin decreased at old age in AL rats, while no changes were evident in CR rats across age groups. CONCLUSIONS: IL-15 signaling could therefore represent a potential target for interventions to counteract metabolic alterations and the deterioration of body composition during aging.

Aims/hypothesis The identification of mediators in the pathogenesis of type 2 diabetes mellitus is essential for the full understanding of this disease. Protein kinases are especially important because of their potential as pharmacological targets. The goal of this study was to investigate whether mammalian sterile-20 3 (MST3/STK24), a stress-regulated kinase, is involved in metabolic alterations in obesity. Methods Glucose regulation of Mst3 (also known as Stk24)-knockout mice was analysed both in 129; C57 mixed background mice and in C57/BL6J mice fed normally or with a high-fat diet (HFD). This work was complemented with an analysis of the insulin signalling pathway in cultured human liver cells made deficient in MST3 using RNA interference. Results MST3 is phosphorylated in the livers of mice subject to an obesity-promoting HFD, and its deficiency lowers the hyperglycaemia, hyperinsulinaemia and insulin resistance that the animals develop with this diet, an effect that is seen even without complete inactivation of the kinase. Lack of MST3 results in activation of the insulin signalling pathway downstream of IRS1, in both cultured liver cells and the liver of animals after HFD. This effect increases the inhibition of forkhead box (FOX) O1, with subsequent downregulation of the expression of gluconeogenic enzymes. Conclusions/interpretation MST3 inhibits the insulin signalling pathway and is important in the development of insulin resistance and impaired blood glucose levels after an HFD.