Glucose‐dependent Insulinotropic Polypeptide (GIP) Stimulates Transepithelial Glucose Transport

Abstract

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 μmol/l), an inhibitor of Na + -glucose cotransporter (SGLT-1), abolished the increase in I SC and decreased J ms 3OMG by ~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.

Metabolic Surgery for Non-Obese Type 2 Diabetes

“…32 The GIP-induced intestinal glucose transport mediated by Na + glucose cotransporter-1 could be elevated in type 2 diabetes, and GIP Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.…”

Sex Steroids Affect Triglyceride Handling, Glucose-Dependent Insulinotropic Polypeptide, and Insulin Sensitivity

“…Effects of sex steroids on GIP have not been reported before. Action of GIP is not limited to pancreatic cells and may affect lipid homeostasis (13) and intestinal glucose transport (14). …”

Sensing Via Intestinal Sweet Taste Pathways

“…Rapidly and slowly digestible carbohydrates are also known to differ considerably in their ability to stimulate GIP secretion indicating that an absorptive pathway is the major route for triggering GIP release in humans (Wachters-Hagedoorn et al, 2006). Indeed GIP may, itself, act to stimulate expression of SGLT-1, based on in vitro evidence in mice (Singh et al, 2008). Ligands that interact at the sweet taste receptor (gurmarin, stevioside) however do not appear to influence in vivo GIP release in rats (Fushiki et al, 1992).…”

“…Such a neural reflex may explain the observation that glucose exposure of isolated regions of the GI tract in rats leads to increased SGLT-1 in non-exposed regions (Stearns et al, 2010). It is also possible that a humoral reflex pathway is triggered by intestinal glucose to modulate distant SGLT-1 expression, for example, GIP release has been proposed as a mechanism linking intestinal sweet taste receptor activation to SGLT-1 regulation in mice (Margolskee et al, 2007; Singh et al, 2008). 5-HT also appears to be involved in this signaling in rats, as the 5-HT 3 receptor antagonist ondansetron reduced accumulation of SGLT-1 in response to glucose (Stearns et al, 2010).…”