Macrophages, cytokines and beta-cell death in Type 2 diabetes.
The pathology of islets from patients with Type 2 diabetes displays an inflammatory process characterized by the presence of immune cell infiltration, cytokines, apoptotic cells, amyloid deposits and, eventually, fibrosis. Indeed, analysis of beta-cells from patients with Type 2 diabetes displays increased IL-1beta (interleukin 1beta) 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 probably attracted by islet-derived chemokines, produced in response to metabolic stress, and under the control of IL-1beta. It follows that modulation of intra-islet inflammatory mediators, particularly interleukin-1beta, may prevent islet inflammation in Type 2 diabetes and therefore presents itself as a promising therapeutic approach.
Ehses
Jan A
JA
Clinic of Endocrinology and Diabetes, and Centre for Integrated Human Physiology, University Hospital of Zurich, CH-8091 Zurich, Switzerland.
Böni-Schnetzler
Marianne
M
Faulenbach
Mirjam
M
Donath
Marc Y
MY
D000818:Animals; D016923:Cell Death; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000473:pathology*; D008954:Models, Biological
D053583:Interleukin-1beta