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

IF 3.5 4区生物学 Q1 Biochemistry, Genetics and Molecular Biology FEBS Letters Pub Date : 2024-08-02 DOI:10.1002/1873-3468.14977

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

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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.

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非肥胖型 2 型糖尿病后藤柿崎大鼠的胰岛素抵抗与促炎性 T 淋巴细胞特征有关。

Goto-Kakizaki (GK) 大鼠会产生明确的胰岛素抵抗（IR）和 2 型糖尿病（T2DM），但不会出现肥胖。非肥胖糖尿病大鼠的淋巴细胞特征尚未确定。因此，与 Wistar 大鼠相比，我们选择 GK 大鼠来研究不同阶段（21、60 和 120 天）的 T 淋巴细胞（TL）动态。GK 大鼠表现出葡萄糖调节的渐进性破坏，21 天时出现早期葡萄糖不耐受，60 天时胰岛素敏感性降低，证实了 IR。葡萄糖转运体 1 (GLUT1) 的表达在 GK 大鼠中持续升高，表明 TL 激活增强。T 调节淋巴细胞标志物在 21 天时减少。然而，GK 大鼠在 120 天时 Th1 标志物增加，Gata-3 表达（对 Th2 细胞分化至关重要）减少。这些发现强调了 GK 大鼠抗炎机制的早期崩溃，表明其 TL 特征可能会加重 T2DM 的慢性炎症。

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

7.00

自引率

2.90%

发文量

303

审稿时长

1.0 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.