High Glycemic Index Metabolic Damage – a Pivotal Role of GIP and GLP-1

• Published in: Trends in endocrinology and metabolism Vol. 29; no. 5; pp. 289 - 299
• Main Authors: Pfeiffer, Andreas F.H., Keyhani-Nejad, Farnaz
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.05.2018
• Subjects: Animals; Gastric Inhibitory Polypeptide - metabolism; Glucagon-Like Peptide 1 - metabolism; glucose-induced insulinotropic peptide; Glycemic Index; Humans; incretin; Incretins - metabolism; Inflammation - metabolism; Insulin - metabolism; isomaltulose; Muscle, Skeletal - metabolism; Postprandial Period; saccharose; glycemic index; glucose-induced insulinotropic peptide; saccharose; isomaltulose; incretin
• DOI: 10.1016/j.tem.2018.03.003
• ISSN: 1043-2760; 1879-3061

When glucose–fructose dimers are supplied as the slowly digestible, completely absorbable, low glycemic index (GI) sugar isomaltulose, the detrimental effects of high GI sucrose are avoided. This difference requires the presence of intact glucose-induced insulinotropic peptide receptor (GIPR) and is mediated by the rapid uptake of glucose and the stimulation of GIP release from K cells in the upper small intestine. GIP promotes lipogenesis, fatty liver, insulin resistance, and postprandial inflammation, and reduces fat oxidation in skeletal muscle, partly by hypothalamic interference with energy partitioning and epigenetic programming. GIP is similarly required for the detrimental metabolic effects of other high GI carbohydrates. We therefore propose that the release of GIP in the upper small intestine is an important determinant of the metabolic quality of carbohydrates. The GI quantifies the widely variable increases in blood glucose after ingestion of different carbohydrates, with the concept that larger increases cause the development of cardiometabolic diseases. The metabolic effects of sugars depend primarily on the intestinal hormones GIP and GLP-1, which release insulin and regulate metabolic responses such as insulin resistance, adipose tissue subclinical inflammation, hepatic fat accumulation, and postprandial vascular responses. The GIP-releasing K cells are located in the proximal small intestine, while GLP-1 is released by more distally located L cells. Their responses to sugars depend on the site of resorption. GIP has mostly unfavorable, while GLP-1 has beneficial, metabolic and cardiovascular properties. The release of GIP therefore appears to be a primary mediator of the deleterious effects of sugars with a high glycemic index in metabolism.