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

被引：2

作者：

Lobato, Tiago Bertola ^{[1
]}

Manoel, Richelieau ^{[1
]}

Pereira, Ana Carolina Gomes ^{[1
]}

Correa, Ilana Souza ^{[1
]}

Iser-Bem, Patricia Nancy ^{[1
]}

Santos, Elvirah Samantha de Sousa ^{[1
]}

Pereira, Joice Naiara Bertaglia ^{[1
]}

de Araujo, Maria Janaina Leite ^{[1
]}

Borges, Joao Carlos de Oliveira ^{[1
]}

Pauferro, Janaina Ribeiro Barbosa ^{[1
]}

Diniz, Vinicius Leonardo Sousa ^{[1
]}

Scervino, Maria Vitoria Martins ^{[1
]}

Serdan, Tamires Duarte ^{[1
]}

Pithon-Curi, Tania Cristina ^{[1
]}

Masi, Laureane Nunes ^{[1
,2
]}

Hirabara, Sandro Massao ^{[1
]}

Curi, Rui ^{[1
,3
]}

Gorjao, Renata ^{[1
]}

机构：

[1] Univ Cruzeiro Sul, Interdisciplinary Postgrad Program Hlth Sci, Rua Galvao Bueno 868, BR-01506000 Sao Paulo, SP, Brazil

[2] Fed Univ Santa Catarina UFSC, Ctr Biol Sci, Dept Physiol Sci, Florianopolis, Brazil

[3] Butantan Inst, Bioind Ctr, Immunobiol Prod Sect, Sao Paulo, Brazil

来源：

FEBS LETTERS | 2024年 / 598卷 / 20期

基金：

巴西圣保罗研究基金会;

关键词：

inflammation; proliferation; T helper cells; Treg cells; type; 2; diabetes; DIET-INDUCED OBESITY; ADIPOSE-TISSUE; ADAPTIVE IMMUNITY; TNF-ALPHA; INFLAMMATION; TH1; DIFFERENTIATION; METABOLISM; MONOCYTES; PATHWAYS;

D O I：

10.1002/1873-3468.14977

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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

引用

页码：2566 / 2580

页数：15

共 64 条

[11] The signaling adaptors and pathways activated by TNF superfamily [J].

Dempsey, PW ;

Doyle, SE ;

He, JQ ;

Cheng, GH .

CYTOKINE & GROWTH FACTOR REVIEWS, 2003, 14 (3-4) :193-209

[12] Interleukin-23 Facilitates Th1 and Th2 Cell Differentiation In Vitro Following Respiratory Syncytial Virus Infection [J].

Feng, Jingjing ;

Hu, Yunwen ;

Song, Zhigang ;

Liu, Yi ;

Guo, Xuejun ;

Jie, Zhijun .

JOURNAL OF MEDICAL VIROLOGY, 2015, 87 (04) :708-715

[13] Regulation of T lymphocyte metabolism [J].

Frauwirth, KA ;

Thompson, CB .

JOURNAL OF IMMUNOLOGY, 2004, 172 (08) :4661-4665

[14] PRODUCTION OF SPONTANEOUS DIABETIC RATS BY REPETITION OF SELECTIVE BREEDING [J].

GOTO, Y ;

KAKIZAKI, M ;

MASAKI, N .

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE, 1976, 119 (01) :85-90

[15] Inflammation and metabolic disorders [J].

Hotamisligil, Goekhan S. .

NATURE, 2006, 444 (7121) :860-867

[16] Regulation of Differentiation and Function of Helper T Cells by Lymphocyte-Derived Catecholamines via α1- and β2- Adrenoceptors [J].

Huang, Hui-Wei ;

Fang, Xiao-Xia ;

Wang, Xiao-Qin ;

Peng, Yu-Ping ;

Qiu, Yi-Hua .

NEUROIMMUNOMODULATION, 2015, 22 (03) :138-151

[17]

IDF Diabetes Atlas 2021, 2023, IDF DIABETES ATLAS 2

[18] Lymphocyte roles in metabolic dysfunction: of men and mice [J].

Ip, Blanche C. ;

Hogan, Andrew E. ;

Nikolajczyk, Barbara S. .

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2015, 26 (02) :91-100

[19] Elevated Proinflammatory Cytokine Production by a Skewed T Cell Compartment Requires Monocytes and Promotes Inflammation in Type 2 Diabetes [J].

Jagannathan-Bogdan, Madhumita ;

McDonnell, Marie E. ;

Shin, Hyunjin ;

Rehman, Qasim ;

Hasturk, Hatice ;

Apovian, Caroline M. ;

Nikolajczyk, Barbara S. .

JOURNAL OF IMMUNOLOGY, 2011, 186 (02) :1162-1172

[20] Mechanisms linking obesity to insulin resistance and type 2 diabetes [J].

Kahn, Steven E. ;

Hull, Rebecca L. ;

Utzschneider, Kristina M. .

NATURE, 2006, 444 (7121) :840-846

← 1 2 3 4 5 6 7 →