Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, São Paulo, Brazil.
Department of Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina-UFSC, Brazil.
FEBS Lett. 2024 Oct;598(20):2566-2580. doi: 10.1002/1873-3468.14977. Epub 2024 Aug 2.
Goto-Kakizaki (GK) rats develop a well-defined insulin resistance (IR) and type 2 diabetes mellitus (T2DM) without presenting obesity. The lymphocyte profile in nonobese diabetic conditions is not yet characterized. Therefore, GK rats were chosen to explore T lymphocyte (TL) dynamics at various stages (21, 60, and 120 days) compared to Wistar rats. GK rats exhibit progressive disruption of glucose regulation, with early glucose intolerance at 21 days and reduced insulin sensitivity at 60 days, confirming IR. Glucose transporter 1 (GLUT1) expression was consistently elevated in GK rats, suggesting heightened TL activation. T-regulatory lymphocyte markers diminished at 21 days. However, GK rats showed increased Th1 markers and reduced Gata-3 expression (crucial for Th2 cell differentiation) at 120 days. These findings underscore an early breakdown of anti-inflammatory mechanisms in GK rats, indicating a proinflammatory TL profile that may worsen chronic inflammation in T2DM.
Goto-Kakizaki(GK)大鼠在不肥胖的情况下发展出明确的胰岛素抵抗(IR)和 2 型糖尿病(T2DM)。非肥胖型糖尿病条件下的淋巴细胞特征尚未确定。因此,选择 GK 大鼠来研究与 Wistar 大鼠相比在不同阶段(21、60 和 120 天)T 淋巴细胞(TL)的动态变化。GK 大鼠表现出葡萄糖调节逐渐紊乱,21 天出现早期葡萄糖不耐受,60 天胰岛素敏感性降低,证实存在 IR。葡萄糖转运蛋白 1(GLUT1)的表达在 GK 大鼠中持续升高,提示 TL 激活增强。21 天时 T 调节性淋巴细胞标记物减少。然而,GK 大鼠在 120 天时表现出 Th1 标记物增加和 Gata-3 表达减少(对 Th2 细胞分化至关重要)。这些发现强调了 GK 大鼠中抗炎机制的早期崩溃,表明存在促炎 TL 特征,这可能会使 T2DM 中的慢性炎症恶化。