Mercedes Mirecki-Garrido1, Amira Alkharusi2,3, Ma Zuheng2, Fahad Alzadjali3, Amilcar Flores-Morales4, Thomas Nyström2, Anneli Björklund2, Gunnar Norstedt2, 3 and Leandro Fernandez-Pérez1
1Las Palmas de Gran Canaria University, Spain 2Karolinska Institute, Sweden 3Sultan Qaboos University, Oman 4University of Copenhagen, Denmark
Posters-Accepted Abstracts: J Diabetes Metab
Currently there has been a rapid increase in the prevalence of diabetes and associated metabolic disorders. Identifying the molecular mechanisms responsible is essential to develop effective strategies. An insufficient number of insulin-producing β cells is a hallmark of both type 1 and type 2 diabetes. SOCS proteins are powerful inhibitors of pathways involved in survival and function of pancreatic β cells also are potent regulators of pro-insulin processing and insulin secretion in β-cells. Moreover, constitutive production of SOCS-2 in β-cells leads to hyperglycaemia and glucose intolerance. It is the rationale to investigate, how SOCS-2 ablation may influence the development of diabetes in a mice model of autoimmune diabetes and β-cell destruction (multiple lowdose of streptozotocin (MLD-STZ)). To analyze SOCS-2 glucose homeostasis and metabolism, all diabetes development parameters were monitored, and both MLD-STZ-treated SOCS-2-/- and WT mice developed severe diabetes after day 9 from injecting first dose of STZ. However, SOCS-2â??/â?? mice were more resistant to develop diabetes. Also our results suggest higher degree of insulin sensitivity with SOCS-2 ablation. Moreover, we further observed higher fasting plasma insulin and the higher HOMA-IR in MLD-STZ- treated SOCS-2-/- mice. Taken together, the results suggest that SOCS-2 ablation seems to compensate β-cell destruction induced by MLDSTZ. The insulin immunostaining assays showed that SOCS-2-/- pancreas have higher β-cell mass and bigger islets size than the control WT pancreas. These results seems to explain the augmented serum insulin levels observed in SOCS-2-/-, also when treated with the STZ a destruction in the β-cell of the WT was observed, but some conserved structures could be find in the SOCS-2-/-. In summary, this study identified SOCS-2 as an important regulator of insulin homeostasis in vivo and suggests that inhibition of SOCS- 2 may be used as therapeutic target to ameliorate diabetes development.
Email: m.mirecki@me.com
