TY - JOUR

T1 - Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans

AU - Kuhre, Rune Ehrenreich

AU - Gribble, Fiona M

AU - Hartmann, Bolette

AU - Reimann, Frank

AU - Windeløv, Johanne A

AU - Rehfeld, Jens F

AU - Holst, Jens Juul

PY - 2014/4/1

Y1 - 2014/4/1

N2 - Nutrients often stimulate gut hormone secretion, but the effects of fructose are incompletely understood. We studied the effects of fructose on a number of gut hormones with particular focus on glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In healthy humans, fructose intake caused a rise in blood glucose and plasma insulin and GLP-1, albeit to a lower degree than isocaloric glucose. Cholecystokinin secretion was stimulated similarly by both carbohydrates, but neither peptide YY3-36 nor glucagon secretion was affected by either treatment. Remarkably, while glucose potently stimulated GIP release, fructose was without effect. Similar patterns were found in the mouse and rat, with both fructose and glucose stimulating GLP-1 secretion, whereas only glucose caused GIP secretion. In GLUTag cells, a murine cell line used as model for L cells, fructose was metabolized and stimulated GLP-1 secretion dose-dependently (EC50 = 0.155 mM) by ATP-sensitive potassium channel closure and cell depolarization. Because fructose elicits GLP-1 secretion without simultaneous release of glucagonotropic GIP, the pathways underlying fructose-stimulated GLP-1 release might be useful targets for type 2 diabetes mellitus and obesity drug development.

AB - Nutrients often stimulate gut hormone secretion, but the effects of fructose are incompletely understood. We studied the effects of fructose on a number of gut hormones with particular focus on glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In healthy humans, fructose intake caused a rise in blood glucose and plasma insulin and GLP-1, albeit to a lower degree than isocaloric glucose. Cholecystokinin secretion was stimulated similarly by both carbohydrates, but neither peptide YY3-36 nor glucagon secretion was affected by either treatment. Remarkably, while glucose potently stimulated GIP release, fructose was without effect. Similar patterns were found in the mouse and rat, with both fructose and glucose stimulating GLP-1 secretion, whereas only glucose caused GIP secretion. In GLUTag cells, a murine cell line used as model for L cells, fructose was metabolized and stimulated GLP-1 secretion dose-dependently (EC50 = 0.155 mM) by ATP-sensitive potassium channel closure and cell depolarization. Because fructose elicits GLP-1 secretion without simultaneous release of glucagonotropic GIP, the pathways underlying fructose-stimulated GLP-1 release might be useful targets for type 2 diabetes mellitus and obesity drug development.

KW - Administration, Oral

KW - Adult

KW - Animals

KW - Blood Glucose

KW - Cell Line

KW - Cholecystokinin

KW - Dietary Carbohydrates

KW - Dose-Response Relationship, Drug

KW - Enteroendocrine Cells

KW - Female

KW - Fructose

KW - Gastric Inhibitory Polypeptide

KW - Glucagon

KW - Glucagon-Like Peptide 1

KW - Humans

KW - Insulin

KW - Intestines

KW - Ion Channel Gating

KW - KATP Channels

KW - Male

KW - Membrane Potentials

KW - Mice

KW - Mice, Inbred C57BL

KW - Rats

KW - Rats, Wistar

KW - Single-Blind Method

KW - Time Factors

KW - Young Adult

U2 - 10.1152/ajpgi.00372.2013

DO - 10.1152/ajpgi.00372.2013

M3 - Journal article

C2 - 24525020

VL - 306

SP - G622-30

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 7

ER -