On the physiology of GIP and GLP-1.
Recent studies have indicated that GIP and GLP-1 are about as important as each other in the incretin effect, being released rapidly after meals and being active already at fasting glucose levels. Although the density of GLP-1 producing cells is higher distally, GlP-1 is normally secreted by jejunal L-cells, explaining the rapid onset of secretion. Moreover, many endocrine cells in the small intestine appear to produce both GIP and GLP-1. Both are metabolized rapidly by the dipeptidyl peptidase IV enzyme, but unlike GIP, about 90 % of GLP-1 is degraded before it reaches the systemic circulation. Apparently, before it is degraded, GLP-1 activates sensory afferents in the gastrointestinal mucosa with cell bodies in the nodose ganglion, signaling onwards to the brain stem and the hypothalamus. A similar mechanism seems to be involved in GLP-1's effect on gastrointestinal motility and secretion, and perhaps its actions on appetite and food intake, all of which may be even more physiologically important than its effects on the beta cells. Cardiovascular and neuroprotective actions of GLP-1 have also recently been reported. Regarding GIP, several lines of evidence suggest that GIP, in addition to its incretin effects, may affect lipid metabolism and promote lipid storage.
Holst
J J
JJ
Department of Medical Physiology, University of Copenhagen, 2200 Copenhagen N, Denmark. holst@mfi.ku.dk
D000818:Animals; D001066:Appetite / Q000502:physiology; D002319:Cardiovascular System; D005749:Gastric Inhibitory Polypeptide / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology; D005934:Glucagon / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007421:Intestine, Small / Q000502:physiology; D007583:Jejunum / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009490:Neurosecretory Systems; D010446:Peptide Fragments / Q000502:physiology*; D011498:Protein Precursors / Q000502:physiology*
D010446:Peptide Fragments; D011498:Protein Precursors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon