A Holistic View of the Goto-Kakizaki Rat Immune System: Decreased Circulating Immune Markers in Non- Obese Type 2 Diabetes

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Jun 9

PMID 35677049

Authors

Snehaa V Seal

Mathilde Henry

Clementine Pajot

Cyrielle Holuka

Danielle Bailbe

Jamileh Movassat

Muriel Darnaudery

Jonathan D Turner

Affiliations

Soon will be listed here.

Abstract

Type-2 diabetes is a complex disorder that is now considered to have an immune component, with functional impairments in many immune cell types. Type-2 diabetes is often accompanied by comorbid obesity, which is associated with low grade inflammation. However,the immune status in Type-2 diabetes independent of obesity remains unclear. Goto-Kakizaki rats are a non-obese Type-2 diabetes model. The limited evidence available suggests that Goto-Kakizaki rats have a pro-inflammatory immune profile in pancreatic islets. Here we present a detailed overview of the adult Goto-Kakizaki rat immune system. Three converging lines of evidence: fewer pro-inflammatory cells, lower levels of circulating pro-inflammatory cytokines, and a clear downregulation of pro-inflammatory signalling in liver, muscle and adipose tissues indicate a limited pro-inflammatory baseline immune profile outside the pancreas. As Type-2 diabetes is frequently associated with obesity and adipocyte-released inflammatory mediators, the pro-inflammatory milieu seems not due to Type-2 diabetes ; although this overall reduction of immune markers suggests marked immune dysfunction in Goto-Kakizaki rats.

Citing Articles

Omega-3 Fatty Acids Weaken Lymphocyte Inflammatory Features and Improve Glycemic Control in Nonobese Diabetic Goto-Kakizaki Rats.

Lobato T, Santos E, Iser-Bem P, Falcao H, Gimenes G, Pauferro J Nutrients. 2024; 16(23).

PMID: 39683500 PMC: 11644024. DOI: 10.3390/nu16234106.

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs.

Janapati Y, Junapudi S Animal Model Exp Med. 2024; 7(3):297-309.

PMID: 38837635 PMC: 11228097. DOI: 10.1002/ame2.12442.

High-fat-diet induced obesity and diabetes mellitus in Th1 and Th2 biased mice strains: A brief overview and hypothesis.

Somi Sankaran P Chronic Dis Transl Med. 2023; 9(1):14-19.

PMID: 36926255 PMC: 10011668. DOI: 10.1002/cdt3.57.

References

Pfeiffer A, Janott J, Mohlig M, Ristow M, Rochlitz H, Busch K . Circulating tumor necrosis factor alpha is elevated in male but not in female patients with type II diabetes mellitus. Horm Metab Res. 1997; 29(3):111-4. DOI: 10.1055/s-2007-979001. View

Lasselin J, Capuron L . Chronic low-grade inflammation in metabolic disorders: relevance for behavioral symptoms. Neuroimmunomodulation. 2014; 21(2-3):95-101. DOI: 10.1159/000356535. View

Liang Y, Pan H, Ye D . Tc17 Cells in Immunity and Systemic Autoimmunity. Int Rev Immunol. 2014; 34(4):318-31. DOI: 10.3109/08830185.2014.954698. View

Sa V, Silva T, Reis C, Cunha F, Figueiredo F, Bocca A . The pattern of immune cell infiltration in chromoblastomycosis: involvement of macrophage inflammatory protein-1 alpha/CCL3 and fungi persistence. Rev Inst Med Trop Sao Paulo. 2007; 49(1):49-53. DOI: 10.1590/s0036-46652007000100009. View

Greaves D, Hakkinen T, Lucas A, Liddiard K, Jones E, Quinn C . Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus- and activation-regulated chemokine, are expressed in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2001; 21(6):923-9. DOI: 10.1161/01.atv.21.6.923. View

Ehses J, Perren A, Eppler E, Ribaux P, Pospisilik J, Maor-Cahn R . Increased number of islet-associated macrophages in type 2 diabetes. Diabetes. 2007; 56(9):2356-70. DOI: 10.2337/db06-1650. View

Satoh T, Tajima M, Wakita D, Kitamura H, Nishimura T . The development of IL-17/IFN-γ-double producing CTLs from Tc17 cells is driven by epigenetic suppression of Socs3 gene promoter. Eur J Immunol. 2012; 42(9):2329-42. DOI: 10.1002/eji.201142240. View

Damoiseaux J, Cautain B, Bernard I, Mas M, Van Breda Vriesman P, Druet P . A dominant role for the thymus and MHC genes in determining the peripheral CD4/CD8 T cell ratio in the rat. J Immunol. 1999; 163(6):2983-9. View

Takeda Y, Marumo M, Wakabayashi I . Attenuated phagocytic activity of monocytes in type 2 diabetic Goto-Kakizaki rats. Immunobiology. 2011; 216(10):1094-102. DOI: 10.1016/j.imbio.2011.05.003. View

10.

Galvez I, Martin-Cordero L, Hinchado M, Alvarez-Barrientos A, Ortega E . Anti-inflammatory effect of β2 adrenergic stimulation on circulating monocytes with a pro-inflammatory state in high-fat diet-induced obesity. Brain Behav Immun. 2019; 80:564-572. DOI: 10.1016/j.bbi.2019.04.042. View

11.

Portha B, Giroix M, Tourrel-Cuzin C, Le-Stunff H, Movassat J . The GK rat: a prototype for the study of non-overweight type 2 diabetes. Methods Mol Biol. 2012; 933:125-59. DOI: 10.1007/978-1-62703-068-7_9. View

12.

Yasuda K, Nakanishi K, Tsutsui H . Interleukin-18 in Health and Disease. Int J Mol Sci. 2019; 20(3). PMC: 6387150. DOI: 10.3390/ijms20030649. View

13.

Mahlangu T, Dludla P, Nyambuya T, Mxinwa V, Mazibuko-Mbeje S, Cirilli I . A systematic review on the functional role of Th1/Th2 cytokines in type 2 diabetes and related metabolic complications. Cytokine. 2019; 126:154892. DOI: 10.1016/j.cyto.2019.154892. View

14.

Chellappa S, Hugenschmidt H, Hagness M, Subramani S, Melum E, Line P . CD8+ T Cells That Coexpress RORγt and T-bet Are Functionally Impaired and Expand in Patients with Distal Bile Duct Cancer. J Immunol. 2017; 198(4):1729-1739. DOI: 10.4049/jimmunol.1600061. View

15.

Nikoulina S, Ciaraldi T, Mudaliar S, Mohideen P, Carter L, Henry R . Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes. Diabetes. 2000; 49(2):263-71. DOI: 10.2337/diabetes.49.2.263. View

16.

Chang C, Wu C, Su W, Shih K, Tarng D, Chou C . Interferon gamma-induced protein 10 is associated with insulin resistance and incident diabetes in patients with nonalcoholic fatty liver disease. Sci Rep. 2015; 5:10096. PMC: 4426720. DOI: 10.1038/srep10096. View

17.

Palanivel R, Fullerton M, Galic S, Honeyman J, Hewitt K, Jorgensen S . Reduced Socs3 expression in adipose tissue protects female mice against obesity-induced insulin resistance. Diabetologia. 2012; 55(11):3083-93. PMC: 5233443. DOI: 10.1007/s00125-012-2665-3. View

18.

Miya A, Nakamura A, Miyoshi H, Takano Y, Sunagoya K, Hayasaka K . Impact of Glucose Loading on Variations in CD4 and CD8 T Cells in Japanese Participants with or without Type 2 Diabetes. Front Endocrinol (Lausanne). 2018; 9:81. PMC: 5870166. DOI: 10.3389/fendo.2018.00081. View

19.

Jain S, Kahlon G, Morehead L, Lieblong B, Stapleton T, Hoeldtke R . The effect of sleep apnea and insomnia on blood levels of leptin, insulin resistance, IP-10, and hydrogen sulfide in type 2 diabetic patients. Metab Syndr Relat Disord. 2012; 10(5):331-6. PMC: 3503462. DOI: 10.1089/met.2012.0045. View

20.

Bhat P, Leggatt G, Waterhouse N, Frazer I . Interferon-γ derived from cytotoxic lymphocytes directly enhances their motility and cytotoxicity. Cell Death Dis. 2017; 8(6):e2836. PMC: 5520949. DOI: 10.1038/cddis.2017.67. View