Journal article
Association of proinflammatory cytokines and islet resident leucocytes with islet dysfunction in type 2 diabetes
Diabetologia, Vol.57(3), pp.491-501
2014
DOI: 10.1007/s00125-013-3116-5
PMCID: PMC3966210
PMID: 24429578
Abstract
Aims/hypothesis: Chronic inflammation in type 2 diabetes is proposed to affect islets as well as insulin target organs. However, the nature of islet inflammation and its effects on islet function in type 2 diabetes remain unclear. Moreover, the immune cell profiles of human islets in healthy and type 2 diabetic conditions are undefined. We aimed to investigate the correlation between proinflammatory cytokine expression, islet leucocyte composition and insulin secretion in type 2 diabetic human islets.
Methods: Human islets from organ donors with or without type 2 diabetes were studied. First and second phases of glucose-stimulated insulin secretion were determined by perifusion. The expression of inflammatory markers was obtained by quantitative PCR. Immune cells within human islets were analysed by FACS.
Results: Type 2 diabetic islets, especially those without first-phase insulin secretion, displayed higher CCL2 and TNFa expression than healthy islets. CD45(+) leucocytes were elevated in type 2 diabetic islets, to a greater extent in moderately functional type 2 diabetic islets compared with poorly functional ones, and corresponded with elevated ALOX12 but not with CCL2 or TNFa expression. T and B lymphocytes and CD11c(+) cells were detectable within both non-diabetic and type 2 diabetic islet leucocytes. Importantly, the proportion of B cells was significantly elevated within type 2 diabetic islets.
Conclusions/interpretation: Elevated total islet leucocyte content and proinflammatory mediators correlated with islet dysfunction, suggesting that heterogeneous insulitis occurs during the development of islet dysfunction in type 2 diabetes. In addition, the altered B cell content highlights a potential role for the adaptive immune response in islet dysfunction.
Details
- Title: Subtitle
- Association of proinflammatory cytokines and islet resident leucocytes with islet dysfunction in type 2 diabetes
- Creators
- Matthew J BUTCHER - Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, United StatesDaniel HALLINGER - Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, United StatesEden GARCIA - Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, United StatesYui MACHIDA - Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, United StatesSwarup CHAKRABARTI - Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, United StatesJerry NADLER - Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, United StatesElena V GALKINA - Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, United StatesYumi IMAI - Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23507-1696, United States
- Resource Type
- Journal article
- Publication Details
- Diabetologia, Vol.57(3), pp.491-501
- Publisher
- Springer
- DOI
- 10.1007/s00125-013-3116-5
- PMID
- 24429578
- PMCID
- PMC3966210
- ISSN
- 0012-186X
- eISSN
- 1432-0428
- Language
- English
- Date published
- 2014
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094875602771
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