Abstract
Aim: To study the role of crosstalk between SOCS3 and leptin on insulin expression in rat insulinoma (RIN-5AH) cells that inducibly express SOCS3 mRNA. Materials and Methods: SOCS3 and preproinsulin mRNA expression induced by 5 μM ponasterone A, and the effects of leptin on SOCS3 and preproinsulin mRNA levels were detected by RT-PCR and quantitative PCR, respectively. The effects of SOCS3 on STAT3 phosphorylation were investigated by Western blot analysis. Results: We discovered that SOCS3 regulates preproinsulin mRNA levels in a dose-dependent and timedependent manner. The insulin-suppressing effect of leptin appears to be mediated through reducing the suppressive effects of SOCS3 on STAT3 phosphorylation. Conclusion: Our findings suggest that leptin inhibits preproinsulin mRNA expression induced by SOCS3 in RIN-5AH beta-cells.
Highlights
Obesity is a major cause of the increasing morbidity and mortality associated with diseases such as type-2 diabetes and cardiovascular disease
Using an adipocyte model derived from fibroblasts of wild-type and SOCS3-deficient mouse embryos, Shi et al investigated the role of endogenous SOCS3 in insulin signaling
We discovered that SOCS3 regulates preproinsulin mRNA levels in a dose- and time-dependent manner
Summary
Obesity is a major cause of the increasing morbidity and mortality associated with diseases such as type-2 diabetes and cardiovascular disease. Leptin and insulin, which are key hormones involved in the regulation of energy production and glucose homeostasis, play roles in the pathogenesis of type-2 diabetes. SOCS3 has been reported to affect the signaling of both leptin and insulin. SOCS3 does not alter the levels of the leptin receptor but binds to Tyr985 on the receptor to suppress STAT3 signaling [8,9]. SOCS3 binds to Tyr960 on the insulin receptor and prevents STAT5b activation in adipocytes [11]. Using an adipocyte model derived from fibroblasts of wild-type and SOCS3-deficient mouse embryos, Shi et al investigated the role of endogenous SOCS3 in insulin signaling. SOCS3 deficiency leads to increased insulinstimulated glucose uptake in adipocytes [12]. Overexpression of SOCS3 results in reduced glucose uptake and lipogenesis in adipocytes [13]. Given its regulatory effects in both the leptin and insulin pathways, SOCS3 is likely to be a key node in the crosstalk between the leptin and insulin signaling cascades
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