Journal
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
Volume 18, Issue 4, Pages 381-388Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MCO.0000000000000187
Keywords
bariatric surgery; diabetes; gut hormones; hyperglycemia; incretins; insulin; receptors; transporters
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Purpose of review Nutrient-specific sensor systems in enteroendocrine cells detect intestinal contents and cause gut hormone release upon activation. Among these peptide hormones, the incretins glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 are of particular interest by their role in glucose homeostasis, metabolic control and for proper beta-cell function. This review focuses on intestinal nutrient-sensing processes and their role in health and disease. Recent findings All macronutrients, respectively, their digestion products can cause incretin release by targeting specific sensors. Luminal glucose is the strongest stimulant for incretin release with the Na+-dependent glucose transporter as the prime sensor. For peptides, the H+-dependent peptide transporter together with calcium-sensing-receptor act as a sensing system. That transporters can function as nutrient-sensing 'transceptors' is conceptually new as G-protein coupled receptors so far were thought to be the sensing entities. This still holds true for GPR40 and GPR120 as sensors for medium/long-chain fatty acids and GPR41 and GPR43 for microbiota-derived short-chain fatty acids. Synthetic agonists for these receptors show impressive effects on glucagon-like peptide 1 output and glycemic control. Moreover, the remarkable and immediate antidiabetic effects of bariatric surgery/gastric bypass put intestinal nutrient sensing into focus of new strategies for metabolic control. Summary Targeting the intestinal nutrient-sensing machinery by dietary and/or pharmacological means holds promises in particular for treatment of type 2 diabetes. This interest may help to better understand the nutrient-sensing processes and the involvement of the intestine in overall endocrine, neuronal and metabolic control.
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