Insulin secretion in health and disease: nutrients dictate the pace

摘要

Insulin is a key hormone controlling metabolic homeostasis. Loss or dysfunction of pancreatic ?2-cells lead to the release of insufficient insulin to cover the organism needs, promoting diabetes development. Since dietary nutrients influence the activity of ?2-cells, their inadequate intake, absorption and/or utilisation can be detrimental. This review will highlight the physiological and pathological effects of nutrients on insulin secretion and discuss the underlying mechanisms. Glucose uptake and metabolism in ?2-cells trigger insulin secretion. This effect of glucose is potentiated by amino acids and fatty acids, as well as by entero-endocrine hormones and neuropeptides released by the digestive tract in response to nutrients. Glucose controls also basal and compensatory ?2-cell proliferation and, along with fatty acids, regulates insulin biosynthesis. If in the short-term nutrients promote ?2-cell activities, chronic exposure to nutrients can be detrimental to ?2-cells and causes reduced insulin transcription, increased basal secretion and impaired insulin release in response to stimulatory glucose concentrations, with a consequent increase in diabetes risk. Likewise, suboptimal early-life nutrition (e.g. parental high-fat or low-protein diet) causes altered ?2-cell mass and function in adulthood. The mechanisms mediating nutrient-induced ?2-cell dysfunction include transcriptional, post-transcriptional and translational modifications of genes involved in insulin biosynthesis and secretion, carbohydrate and lipid metabolism, cell differentiation, proliferation and survival. Altered expression of these genes is partly caused by changes in non-coding RNA transcripts induced by unbalanced nutrient uptake. A better understanding of the mechanisms leading to ?2-cell dysfunction will be critical to improve treatment and find a cure for diabetes.