Abstract
During fasting conditions, glucose metabolism is maintained through a fine balance between endogenous glucose production from the liver (80%) and kidney (20%) and glucose utilization by body tissues. After the ingestion of a meal, the rise in plasma glucose and insulin, together to gut factors, combine to suppress endogenous glucose production and stimulate glucose uptake in adipose tissue and muscle. The liver (hepatic glucose production) is more sensitive to the inhibitory action of insulin than are peripheral tissues (glucose uptake) to the stimulatory action of insulin. Glucose metabolism is dependent upon the coordinate activation of the insulin signal transduction system, glucose transport/phosphorylation and oxidation by the pyruvate dehydrogenase complex and the mitochondrial chain. Insulin action on glucose metabolism is both direct (stimulation of glucose transport, glycolysis, and glycogen synthesis) and indirect (inhibition of lipolysis, lipid oxidation, and protein degradation). In insulin-sensitive tissues, the three major substrates (glucose, FFAs, amino acids) are in competition with one another. Glucagon plays a role in the tonic support of hepatic glucose production and is also the leading counterregulatory mechanism activated in the defense against hypoglycemia. The amplification of insulin secretion during an oral test is attributed to the nutrient-stimulated release of incretin hormones and their physiological actions, including potentiation of glucose-induced insulin secretion, suppression of glucagon release, inhibition of gastric emptying, and enhancement of satiety. GLP-1 directly, and indirectly by increasing insulin and inhibiting glucagon, augments hepatic glucose uptake and inhibits hepatic glucose production.
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Ferrannini, E., Seghieri, M. (2018). Overview of Glucose Homeostasis. In: Bonora, E., DeFronzo, R. (eds) Diabetes. Epidemiology, Genetics, Pathogenesis, Diagnosis, Prevention, and Treatment. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-27317-4_1-1
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