Insulin resistance in nonobese type 2 diabetic Goto Kakizaki rats is associated with a proinflammatory T lymphocyte profile

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Lobato, Tiago Bertola ; Manoel, Richelieau ; Pereira, Ana Carolina Gomes ; Correa, Ilana Souza ; Iser-Bem, Patricia Nancy ; Santos, Elvirah Samantha de Sousa ; Pereira, Joice Naiara Bertaglia ; de Araujo, Maria Janaina Leite ; Borges, Joao Carlos de Oliveira ; Pauferro, Janaina Ribeiro Barbosa ; Diniz, Vinicius Leonardo Sousa ; Scervino, Maria Vitoria Martins ; Serdan, Tamires Duarte ; Pithon-Curi, Tania Cristina ; Masi, Laureane Nunes ; Hirabara, Sandro Massao ; Curi, Rui ; Gorjao, Renata

• Document type: Journal article
• Source: FEBS Letters; v. 598, n. 20, p. 15-pg., 2024-08-02.

Abstract

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. T lymphocyte differentiation in Goto-Kakizaki rats is compromised from 21, 60, and 120 days, indicating early onset of type 2 diabetes (T2DM). Younger rats exhibit reduced Th2 and T-regulatory markers. Adults (120 days) show increased Th1 markers and decreased expression of Gata-3 (transcription factor crucial for Th2 cell differentiation), likely causing T lymphocyte dysfunction. This imbalance may impair regulatory control of the adaptive immune system in nonobese T2DM individuals. image (AU)

• FAPESP's process: 18/09868-7 - Cellular and molecular mechanisms of insulin resistance and inflammation in obese Wistar rats and lean Goto-Kakizaki rats: causes and associations with diet and physical exercise
• Grantee: Rui Curi
• Support Opportunities: Research Projects - Thematic Grants