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Role of IL-1beta in type 2 diabetes


Dinarello, C A; Donath, M Y; Mandrup-Poulsen, T (2010). Role of IL-1beta in type 2 diabetes. Current Opinion in Endocrinology, Diabetes, and Obesity, 17(4):314-321.

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.

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.

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.

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.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:21 Jan 2011 17:24
Last Modified:05 Apr 2016 14:37
Publisher:Lippincott Wiliams & Wilkins
ISSN:1752-296X
Publisher DOI:https://doi.org/10.1097/MED.0b013e32833bf6dc
PubMed ID:20588114

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