Glucoregulatory relevance of small intestinal nutrient sensing in physiology, bariatric surgery, and pharmacology

Emerging evidence suggests the gastrointestinal tract plays an important glucoregulatory role. In this perspective, we first review how the intestine senses ingested nutrients, initiating crucial negative feedback mechanisms through a gut-brain neuronal axis to regulate glycemia, mainly via reduction in hepatic glucose production. We then highlight how intestinal energy sensory mechanisms are responsible for the glucose-lowering effects of bariatric surgery, specifically duodenal-jejunal bypass, and the antidiabetic agents metformin and resveratrol. A better understanding of these pathways lays the groundwork for intestinally targeted drug therapy for the treatment of diabetes.