Early variations in plasma insulin-like peptide 5 during the oral glucose tolerance test: an exploratory study to further support the role of the proximal intestine in the regulation of food intake in obesity

Introduction: Following the identification of the incretin effect, the role of the enterohormones in regulating food intake and energy balance was recognized, ushering in a new era in the pharmacotherapy of metabolic diseases. A constellation of hormones is released from the gastrointestinal tract, some of them with biological functions still not completely defined. The insulin-like peptide 5 (INSL5) is a recently discovered enterohormone with basic studies proposing a role in the gut-brain axis and hunger regulation, although evidence in humans remains limited. It is primarily produced in the distal colon, but growing reports suggest that its secretion may also be regulated to a proximal level. Methods/Results: We tested this hypothesis through hormone determination during an oral glucose tolerance test in a cohort of patients with severe obesity, observing an early decrease in plasma levels that overlapped with changes in blood glucose and insulin, supporting the idea that INSL5 could also represent a glucose/nutrient-responsive appetite-regulating hormone involved in food seeking. Conclusions: Far from establishing a direct role for gastric-jejunal mucosa or a gastric-colonic cross-talk after food ingestion, our results may incentivize future studies to confirm and validate these findings, and to explore INSL5 as a potential adjunctive target for obesity treatment.