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.
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.
Authors: Susan J Burke; Danhong Lu; Tim E Sparer; Thomas Masi; Matthew R Goff; Michael D Karlstad; J Jason Collier Journal: Am J Physiol Endocrinol Metab Date: 2013-11-26 Impact factor: 4.310
Authors: Alberto Baroja-Mazo; Fatima Martín-Sánchez; Ana I Gomez; Carlos M Martínez; Joaquín Amores-Iniesta; Vincent Compan; Maria Barberà-Cremades; Jordi Yagüe; Estibaliz Ruiz-Ortiz; Jordi Antón; Segundo Buján; Isabelle Couillin; David Brough; Juan I Arostegui; Pablo Pelegrín Journal: Nat Immunol Date: 2014-06-22 Impact factor: 25.606
Authors: V J Auer; E Janas; V Ninichuk; E Eppler; T S Weiss; S Kirchner; A M Otto; M J Stangl Journal: Clin Exp Immunol Date: 2012-11 Impact factor: 4.330