Insulin resistance in nonobese type 2 diabetic GotoKakizaki rats is associated with a proinflammatoryT lymphocyte profile

Abstract

Goto-Kakizaki (GK) rats develop a well-defined insulin resistance (IR) andtype 2 diabetes mellitus (T2DM) without presenting obesity. The lymphocyteprofile in nonobese diabetic conditions is not yet characterized. Therefore,GK rats were chosen to explore T lymphocyte (TL) dynamics at variousstages (21, 60, and 120 days) compared to Wistar rats. GK rats exhibit progressive disruption of glucose regulation, with early glucose intolerance at21 days and reduced insulin sensitivity at 60 days, confirming IR. Glucosetransporter 1 (GLUT1) expression was consistently elevated in GK rats, sug-gesting heightened TL activation. T-regulatory lymphocyte markers dimin-ished at 21 days. However, GK rats showed increased Th1 markers andreduced Gata-3 expression (crucial for Th2 cell differentiation) at 120 days.These findings underscore an early breakdown of anti-inflammatory mecha-nisms in GK rats, indicating a proinflammatory TL profile that may worsenchronic inflammation in T2DM.