Insulitis in type 2 diabetes.
Islets of patients with type 2 diabetes have the feature of an inflammatory process reflected by the presence of cytokines, immune cells, beta-cell apoptosis, amyloid deposits and fibrosis. Indeed, beta-cells from patients with type 2 diabetes display inflammatory markers, including increased interleukin (IL)-1 beta expression. Furthermore, increased islet-associated macrophages are observed in human type 2 diabetic patients and in most animal models of diabetes. Importantly, increased numbers of macrophages are detectable very early in high fat-fed mice islets, before the onset of diabetes. These immune cells are most likely attracted by islet-derived chemokines, produced in response to metabolic stress, and under the control of IL-1 beta. It follows that modulation of intra-islet inflammatory mediators, in particular IL-1 beta, may prevent insulitis in type 2 diabetes and therefore presents itself as a possible causal therapy with disease-modifying potential.
Clinic of Endocrinology and Diabetes and Centre for Integrated Human Physiology, University Hospital of Zurich, Zurich, Switzerland.
M
M
Böni-Schnetzler
J A
JA
Ehses
M
M
Faulenbach
M Y
MY
Donath
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000096:biosynthesis / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats
D007328:Insulin; D053583:Interleukin-1beta; D005934:Glucagon