Interleukin-1 receptor antagonist improves normoglycemia and insulin sensitivity in diabetic Goto-Kakizaki-rats

Type 2 diabetes mellitus has been considered as an auto-inflammatory syndrome. Interleukin-1 receptor antagonist (IL-1Ra) has attained considerable attention due to its broad spectrum anti-inflammatory therapeutic effects against various auto-immune diseases. The purpose of our study was to investigate its therapeutic effects of IL-1Ra on none-obese diabetic Goto-Kakizaki (GK) rats. We administered IL-1Ra subcutaneously for one month into GK rats. Insulin sensitivity and beta-cell function was calculated by homeostatic model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) models. IL-1Ra decreased the onset of hyperglycemia and did not impact the body weight and/or food intake. Insulin tolerance test (ITT) and intraperitoneal glucose tolerance test (IPGTT) results showed that IL-1Ra improved insulin sensitivity and glucose tolerance. The results of HOMA and QUICKI models revealed that IL-1Ra improved insulin sensitivity and beta-cell function. Moreover, significant reduction of pro-insulin/insulin ratio and lipid profiles also exhibited significant therapeutic effects of IL-1Ra. Immunohistochemical analysis showed minimal macrophage infiltration in pancreatic islets demonstrating decreased intra-islet inflammation in IL-1Ra treated GK rats. The results of our present study revealed that IL-1Ra has broad spectrum therapeutic potentials but due to its short biological half-life (6-8 h) high doses with frequent dosing intervals are required. Therefore, there is a need for the development of such dosage form that may prolong its half-life via extended release. (C) 2013 Elsevier B.V. All rights reserved.