TY - JOUR
T1 - Role of IL-1beta in type 2 diabetes
AU - Dinarello, Charles A
AU - Donath, Marc Y
AU - Mandrup-Poulsen, Thomas
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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-1β. RECENT FINDINGS: Recent studies from animals, in-vitro cultures and clinical trials provide evidence that support a causative role for IL-1β as the primary agonist in the loss of beta-cell mass in type 2 diabetes. In vitro, IL-1β-mediated autoinflammatory process results in beta-cell death. The autoinflammation is driven by glucose, free fatty acids, leptin, and IL-1β itself. Caspase-1 is required for IL-1β 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-1β 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-1β antibodies, provides proof-of-principle data that reducing IL-1β activity is sufficient for correcting dysfunctional beta-cell production of insulin in type 2 diabetes, including a possibility that suppression of IL-1β-mediated inflammation in the microenvironment of the islet allows for regeneration. SUMMARY: Monotherapy or add-on therapy targeting IL-1β in type 2 diabetes holds promise for long-term benefits in glycemic control and possibly reducing cardiovascular events.
AB - 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-1β. RECENT FINDINGS: Recent studies from animals, in-vitro cultures and clinical trials provide evidence that support a causative role for IL-1β as the primary agonist in the loss of beta-cell mass in type 2 diabetes. In vitro, IL-1β-mediated autoinflammatory process results in beta-cell death. The autoinflammation is driven by glucose, free fatty acids, leptin, and IL-1β itself. Caspase-1 is required for IL-1β 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-1β 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-1β antibodies, provides proof-of-principle data that reducing IL-1β activity is sufficient for correcting dysfunctional beta-cell production of insulin in type 2 diabetes, including a possibility that suppression of IL-1β-mediated inflammation in the microenvironment of the islet allows for regeneration. SUMMARY: Monotherapy or add-on therapy targeting IL-1β in type 2 diabetes holds promise for long-term benefits in glycemic control and possibly reducing cardiovascular events.
KW - Animals
KW - Diabetes Mellitus, Type 2
KW - Humans
KW - Inflammation
KW - Interleukin-1beta
KW - Islets of Langerhans
KW - Models, Biological
U2 - 10.1097/med.0b013e32833bf6dc
DO - 10.1097/med.0b013e32833bf6dc
M3 - Journal article
C2 - 20588114
SN - 1752-296X
VL - 17
SP - 314
EP - 321
JO - Current Opinion in Endocrinology, Diabetes and Obesity
JF - Current Opinion in Endocrinology, Diabetes and Obesity
IS - 4
ER -
