Selective sodium-dependent glucose transporter 1 inhibitors block glucose absorption and impair glucose-dependent insulinotropic peptide release

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 308; no. 11; pp. G946 - G954
• Main Authors: Dobbins, Robert L., Greenway, Frank L., Chen, Lihong, Liu, Yaping, Breed, Sharon L., Andrews, Susan M., Wald, Jeffrey A., Walker, Ann, Smith, Chari D.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2015
• Subjects: 3-O-Methylglucose - pharmacokinetics; Administration, Oral; Adult; Animals; Biological Availability; Clinical trials; Dose-Response Relationship, Drug; Drug Monitoring; Female; Gastric Inhibitory Polypeptide - blood; Glucagon-Like Peptide 1 - blood; Glucose; Glucose - analysis; Glucosides - pharmacokinetics; Humans; Inhibitor drugs; Insulin; Insulin - blood; Intestinal Absorption - drug effects; Intestinal Absorption - physiology; Intestinal Mucosa - metabolism; Intestine, Small - physiology; Male; Middle Aged; Peptides; Physiology; Pyrazoles - pharmacokinetics; Rats; Sodium-Glucose Transporter 1 - antagonists & inhibitors; Treatment Outcome; clinical trial; gastric inhibitory peptide; KGA-2727; GSK-1614235

GSK-1614235 and KGA-2727 are potent, selective inhibitors of the SGLT1 sodium-dependent glucose transporter. Nonclinical (KGA-2727) and clinical (GSK-1614235) trials assessed translation of SGLT1 inhibitor effects from rats to normal human physiology. In rats, KGA-2727 (0.1 mg/kg) or vehicle was giv...