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Role of IL-1beta in type 2 diabetes.
- Source :
-
Current opinion in endocrinology, diabetes, and obesity [Curr Opin Endocrinol Diabetes Obes] 2010 Aug; Vol. 17 (4), pp. 314-21. - Publication Year :
- 2010
-
Abstract
- Purpose of Review: To understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1beta.<br />Recent Findings: Recent studies from animals, in-vitro cultures and clinical trials provide evidence that support a causative role for IL-1beta as the primary agonist in the loss of beta-cell mass in type 2 diabetes. In vitro, IL-1beta-mediated autoinflammatory process results in beta-cell death. The autoinflammation is driven by glucose, free fatty acids, leptin, and IL-1beta itself. Caspase-1 is required for IL-1beta activity and the release of free fatty acids from the adipocyte. An emerging hypothesis gains support from patients with type 2 diabetes in which an imbalance in the amount of IL-1beta agonist activity versus the specific countering by the naturally occurring IL-1 receptor antagonist (IL-1Ra) determines the outcome of islet inflammation. An important confirmation comes from clinical trials. Blockade of IL-1 receptor with anakinra, the recombinant form of IL-1Ra, or neutralizing anti-IL-1beta antibodies, provides proof-of-principle data that reducing IL-1beta activity is sufficient for correcting dysfunctional beta-cell production of insulin in type 2 diabetes, including a possibility that suppression of IL-1beta-mediated inflammation in the microenvironment of the islet allows for regeneration.<br />Summary: Monotherapy or add-on therapy targeting IL-1beta in type 2 diabetes holds promise for long-term benefits in glycemic control and possibly reducing cardiovascular events.
- Subjects :
- Animals
Diabetes Mellitus, Type 2 drug therapy
Diabetes Mellitus, Type 2 genetics
Diabetes Mellitus, Type 2 metabolism
Humans
Inflammation etiology
Inflammation pathology
Interleukin-1beta genetics
Interleukin-1beta metabolism
Interleukin-1beta therapeutic use
Islets of Langerhans immunology
Islets of Langerhans pathology
Models, Biological
Diabetes Mellitus, Type 2 etiology
Interleukin-1beta physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1752-2978
- Volume :
- 17
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Current opinion in endocrinology, diabetes, and obesity
- Publication Type :
- Academic Journal
- Accession number :
- 20588114
- Full Text :
- https://doi.org/10.1097/MED.0b013e32833bf6dc