Antidiabetic Effect of Interleukin-1 beta Antibody Therapy Through beta-Cell Protection in the Cohen Diabetes-Sensitive Rat

作者：Aharon Hananel Genya; Joerns Anne; Lenzen Sigurd; Raz Itamar; Weksler Zangen Sarah^*

来源：Diabetes, 2015, 64(5): 1780-1785.

DOI：10.2337/db14-1018

Interleukin (IL)-1 beta, the sole proinflammatory cytokine released from pancreas-infiltrating macrophages, inhibits glucose-stimulated insulin secretion (GSIS), causing hyperglycemia in Cohen diabetes-sensitive (CDs) rats fed a diabetogenic-diet (CDs-HSD). Because IL-1 beta blockade is a potential therapeutic target in diabetes, we examined whether treating CDs rats with IL-1 beta antibody (IL-1 beta Ab; 0.5 mg/kg body weight) could counteract the inhibition of GSIS and hyperglycemia. We found that daily IL-1 beta Ab injections had a beneficial effect on glucose tolerance and insulin secretion in CDs-HSD rats. In the oral glucose tolerance test, IL-1 beta Ab-treated CDs-HSD rats showed lower blood glucose concentrations (P < 0.001) and higher GSIS (P < 0.05) compared with nontreated CDs-HSD rats. IL-1 beta Ab treatment also protected the exocrine pancreas; the number of infiltrating macrophages decreased by 70% (P < 0.01) and IL-1 beta expression decreased by 85% (P < 0.01). In parallel, a 50% reduction (P < 0.01) in the rate of apoptosis and in fat infiltration (P < 0.05) was noted in the exocrine parenchyma of IL-1 beta Ab-treated CDs-HSD rats compared with nontreated CDs-HSD rats. Altogether, these data demonstrate that blocking IL-1 beta action by IL-1 beta Ab counteracted beta-cell dysfunction and glucose intolerance, supporting the notion that prevention of pancreas infiltration by macrophages producing IL-1 beta is of crucial importance for the preservation of beta-cell function and prevention of diabetes.

• 出版日期2015-5