1955-P: Interleukin-1ß Orchestrates Non–Glucose Dependent Cephalic Phase Insulin Release in Health and Obesity

The non-glucose dependent spike in insulin levels immediately following the beginning of a meal is called the cephalic or pre-absorptive phase of insulin secretion. Even though this early insulin response is of marked consequence for overall postprandial insulin release, its basic mechanisms remain largely unexplored. Here, we show that both genetic and pharmacologic blockade of interleukin-1β (IL-1β) leads to a pronounced reduction in cephalic phase insulin secretion (-0.65 [95%CI= -1.137 to -0.172]). Assessing mice fed a high-fat diet, we found that the cephalic phase insulin response was abolished in obesity. In a systematic review and meta-analysis of trials studying cephalic phase insulin release in healthy human volunteers, we found that this was equally the case in humans. In contrast, high-fat diet-fed mice pre-treated with a specific anti-IL-1β antibody once a week developed no such impairment. We therefore conclude, that dysregulation of physiologic IL-1β signaling, specifically during cephalic phase, may contribute to the overall pathology of metabolic disease. Thus, we identify cephalic phase inflammatory signaling as a novel and potentially modifiable target in the regulation of glucose metabolism.