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

Author:

Lobato Tiago Bertola1ORCID,Manoel Richelieau1ORCID,Pereira Ana Carolina Gomes1ORCID,Correa Ilana Souza1ORCID,Iser‐Bem Patrícia Nancy1ORCID,Santos Elvirah Samantha de Sousa1ORCID,Pereira Joice Naiara Bertaglia1ORCID,de Araújo Maria Janaína Leite1ORCID,Borges João Carlos de Oliveira1ORCID,Pauferro Janaina Ribeiro Barbosa1ORCID,Diniz Vinicius Leonardo Sousa1ORCID,Scervino Maria Vitória Martins1ORCID,Serdan Tamires Duarte1ORCID,Pithon‐Curi Tania Cristina1ORCID,Masi Laureane Nunes12ORCID,Hirabara Sandro Massao1ORCID,Curi Rui13ORCID,Gorjão Renata1ORCID

Affiliation:

1. Interdisciplinary Post‐Graduate Program in Health Sciences Cruzeiro do Sul University São Paulo Brazil

2. Department of Physiological Sciences, Center of Biological Sciences Federal University of Santa Catarina‐UFSC Brazil

3. Immunobiological Production Section, Bioindustrial Center Butantan Institute São Paulo Brazil

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.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Wiley

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