Glucose-dependent insulinotropic polypeptide (GIP) stimulates transepithelial glucose transport.
The purpose of this study was to characterize the effects of glucose-dependent insulinotropic peptide (GIP) on small intestinal glucose transport in vitro. Stripped proximal jejunum from fasted mice was mounted in Ussing chambers. The serosal side was bathed in Regular Ringer solution containing 5 mmol/l glucose, and the mucosal side, with solution containing 10 mmol/l 3-O-methyl glucose (3OMG). Intercellular cyclic adenosine monophosphate (cAMP), mucosa-to-serosa fluxes of 3OMG (J(ms)(3OMG)), and short-circuit current (I(SC)) were measured in the presence and absence of GIP. GIP increased cAMP by 2.5-fold in isolated enterocytes, consistent with a direct effect of GIP on these epithelial cells. GIP also increased I(SC) and J(ms)(3OMG) by 68 and 53%, respectively, indicating that the increase in J(ms)(3OMG) was primarily electrogenic, with a small electroneutral component. The stimulatory effect of GIP on J(ms)(3OMG) was concentration dependent. In addition, 1,000 nmol/l and 10 nmol/l GIP increased J(ms)(3OMG) by 70 and 30% over control, respectively, consistent with receptor activation. Phlorizin (20 mumol/l), an inhibitor of Na(+)-glucose cotransporter (SGLT-1), abolished the increase in I(SC) and decreased J(ms)(3OMG) by approximately 65%. These results indicate that stimulation of SGLT-1 activity by GIP partially accounts for the increase in J(ms)(30MG). These studies are the first to demonstrate direct stimulation of intestinal glucose transport by GIP independent of its insulinotropic properties. GIP stimulates cellular accumulation of cAMP and thereby upregulates glucose transport. The GIP-induced increase in glucose transport appears to be mediated, at least in part, by SGLT-1.
Singh
Satish K
SK
Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. satish.singh@bmc.org
Bartoo
Aaron C
AC
Krishnan
Selvi
S
Boylan
Michael O
MO
Schwartz
John H
JH
Michael Wolfe
M
M
D019325:3-O-Methylglucose / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000378:metabolism / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D010695:Phlorhizin / Q000494:pharmacology; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors / Q000378:metabolism
D005765:Gastrointestinal Agents; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D019325:3-O-Methylglucose; D005749:Gastric Inhibitory Polypeptide; D010695:Phlorhizin; D000242:Cyclic AMP; D005947:Glucose