TY - JOUR

T1 - On the physiology of GIP and GLP-1

AU - Holst, Jens Juul

PY - 2005/1/19

Y1 - 2005/1/19

N2 - 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.

AB - 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.

KW - Animals

KW - Appetite

KW - Cardiovascular System

KW - Gastric Inhibitory Polypeptide

KW - Gastrointestinal Motility

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Intestine, Small

KW - Jejunum

KW - Mice

KW - Mice, Knockout

KW - Neurosecretory Systems

KW - Peptide Fragments

KW - Protein Precursors

U2 - 10.1055/s-2004-826158

DO - 10.1055/s-2004-826158

M3 - Journal article

C2 - 15655703

VL - 36

SP - 747

EP - 754

JO - Hormone and Metabolic Research. Supplement

JF - Hormone and Metabolic Research. Supplement

SN - 0170-5903

IS - 11-12

ER -