Insulin secretion is suppressed by SOCS-2

Suppressor of cytokine signaling (SOCS) proteins are powerful inhibitors of pathways involved in the survival and function of pancreatic beta-cells. Lebrun and colleagues generated transgenic mice in order to investigate the function of SOCS in pancreatic beta-cells. The study showed that SOCS-2 was a potent regulator of proinsulin processing and insulin secretion in beta-cells. Insulin and Proinsulin was measured using the Mercodia Mouse Insulin ELISA and Mercodia Rat/Mouse Proinsulin ELISA, respectively.

Suppressor of cytokine signaling (SOCS) proteins are powerful inhibitors of pathways involved in the survival and function of pancreatic beta-cells. Whereas SOCS-1 and SOCS-3 have been shown to be involved in beta-cell immune and inflammatory processes, respectively, little is known about the role of SOCS-2 in the pancreas. To define whether this protein is implicated in beta-cell functionality and/or survival, Lebrun and co-workers at INSERM in Nice, France generated transgenic mice that constitutively produce SOCS-2 in beta-cells (betaSOCS-2). The results from this study, recently published in Diabetologia, showed that constitutive production of SOCS-2 in beta-cells leads to hyperglycaemia and glucose intolerance. This phenotype is not a consequence of decreased beta-cell mass or inhibition of insulin synthesis. Insulin secretion in response to various secretagogues is also profoundly altered in betaSOCS-2 animals and isolated islets from these animals compared to wt. Interestingly, constitutive SOCS-2 production dampens the rise in glucose-induced cytosolic free calcium concentration, while glucose metabolism remains unchanged. Moreover, transgenic mouse islets show depletion in endoplasmic reticulum Ca²⁺ stores, suggesting that SOCS2 interferes with calcium fluxes. Finally, proinsulin maturation in betaSOCS-2 mice was shown to be impaired, leading to an altered structure of insulin secretory granules and augmented levels of proinsulin. The latter is likely to be due to decreased production of prohormone convertase 1 (PC1/3), which plays a key role in proinsulin cleavage. Thus, the main finding was that SOCS-2 was shown to be a potent regulator of proinsulin processing and insulin secretion in beta-cells. While its constitutive production causes glucose intolerance, it still is insufficient to induce overt diabetes in this mouse model. Thus, increased SOCS2 production may be an important event that increases the risk of beta-cell failure. Insulin and Proinsulin was measured using the Mercodia Mouse Insulin ELISA and Mercodia Rat/Mouse Proinsulin ELISA, respectively.

Lebrun et al. (2010) The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion. Diabetologia 2010 May 25. [Epub ahead of print]