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Insulin: Secretagogues and Nutrient Partitioning
Insulin is the primary anabolic coordinator of nutrient partitioning, and it plays a critical role on carbohydrate, lipid and protein metabolism. Insulin regulates cellular glucose uptake, stimulates glycolysis, and promotes hepatic and muscle glycogen, adipose triglyceride and skeletal muscle protein synthesis; while simultaneously preventing their degradation. Hyperglycemia increases glucose uptake and metabolism by pancreatic β-cells, and this has traditionally been thought of as the main stimulant of insulin secretion. However, other signals are capable of initiating and amplifying this response. For example, nutrients like specific amino acids, fatty acids and keto acids can potentiate pancreatic insulin release. It was thought that internalization and metabolism of these nutrients was required for insulin secretion, however the recent discovery of fatty acids acting through β-cell surface receptors has challenged this dogma. Interestingly, sustained high glucose and fatty acid concentrations result in pancreatic gluco- and lipotoxicity, with detrimental effects on β-cell function and viability. Hormones can also modulate insulin secretion. For example, incretins (glucagon-like peptide-1 and gastric inhibitory peptide) are intestinal hormones with insulinotropic activity, secreted in response to food ingestion; thus integrating diet chemical composition into the regulatory mechanism of insulin release. In addition, prolactin is required for proper islet development and it stimulates β-cell proliferation and increases insulin secretion. This is perplexing as prolactin typically facilitates lactation (although species dependent), while increased systemic insulin action is associated with metabolic adaptions that prevent maximum milk yield. Also counter intuitively, bacterial components might be additional signals influencing insulin secretion. In vivo lipopolysaccharide (LPS) infusion acutely increases circulating insulin, which is paradoxical as endotoxemia is a potent catabolic condition accompanied by severe pyrexia and marked hypophagia. Understanding how and why LPS induces hyperinsulinemia remains to be elucidated, but the practical implications to this phenomenon are numerous. In summary, insulin secretion results from the integration of multiple signals in addition to hyperglycemia. Insulin is a potent anabolic orchestrator of nutrient partitioning, therefore it is critical to understand the regulatory mechanisms of insulin secretion. Further, we need to better understand insulin’s role during certain physiological and pathological conditions, in order to maximize productivity and efficiency in animal agriculture.
Keywords: Insulin, Nutrient partitioning, LPS