Cytokine production by islets in health and diabetes: cellular origin, regulation and function.
Islets produce a variety of cytokines and chemokines in response to physiologic and pathologic stimulation by nutrients. The cellular source of these inflammatory mediators includes alpha-, beta-, endothelial-, ductal- and recruited immune cells. Islet-derived cytokines promote alpha- and beta-cell adaptation and repair in the short term. Eventually, chronic metabolic stress can induce a deleterious autoinflammatory process in islets leading to insulin secretion failure and type 2 diabetes. Understanding the specific role of islet derived cytokines and chemokines has opened the door to targeted clinical interventions aimed at remodeling islet inflammation from destruction to adaptation. In this article, we review the islet cellular origin of various cytokines and chemokines and describe their regulation and respective roles in physiology and diabetes.
Donath
Marc Y
MY
Clinic of Endocrinology and Diabetes, Center for Integrated Human Physiology, University Hospital of Zurich, 8091 Zurich, Switzerland. marc.donath@usz.ch
Böni-Schnetzler
Marianne
M
Ellingsgaard
Helga
H
Halban
Philippe A
PA
Ehses
Jan A
JA
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005786:Gene Expression Regulation; D005947:Glucose / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology; D053583:Interleukin-1beta / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D005947:Glucose