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

American Journal of Physiology. Gastrointestinal and Liver Physiology
Robert L DobbinsChari D Smith

Abstract

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 given before oral administration of 3-O-methyl-α-d-glucopyranose (3-O-methylglucose, 3-OMG) containing 3-[3H]OMG tracer. Tracer absorption and distribution were assessed from plasma, urine, and fecal samples. SGLT1 inhibition reduced urine 3-OMG recovery and increased fecal excretion. SGLT1 inhibitor effects on plasma glucose, insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-1 (GLP-1) concentrations were also measured during a standard meal. Incremental glucose, insulin, and GIP concentrations were decreased, indicating downregulation of β-cell and K cell secretion. Minimal effects were observed in the secretion of the L cell product, GLP-1. With the use of a three-way, crossover design, 12 healthy human subjects received placebo or 20 mg GSK-1614235 immediately before or after a meal. Five minutes into the meal, 3-OMG was ingested. Postmeal dosing had little impact, yet premeal dosing delayed and reduced 3-OMG absor...Continue Reading

References

Mar 1, 1992·Diabetes Research and Clinical Practice·N FukaseH Sasaki
Mar 1, 1970·The Journal of Clinical Investigation·L J ElsasL E Rosenberg
Sep 1, 1965·The American Journal of Physiology·D F Diedrich
Jun 1, 1995·The Journal of Clinical Investigation·M R Uhing, R E Kimura
Feb 15, 2001·Archives of Internal Medicine·UNKNOWN DECODE Study Group, the European Diabetes Epidemiology Group.
Jan 24, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·J DyerS P Shirazi-Beechey
Jul 26, 2002·Cell Biochemistry and Biophysics·Ernest M WrightMartin G Martin
Jan 1, 1957·The American Journal of Physiology·T Z CSAKY, J E GLENN
Jun 1, 1958·Proceedings of the Society for Experimental Biology and Medicine·T Z CSAKY, J E GLENN
Dec 1, 1962·Annals of Internal Medicine·J S FORDTRANF J INGELFINGER
Dec 30, 2004·Diabetes/metabolism Research and Reviews·Joel R L EhrenkranzJesse Roth
Oct 6, 2005·American Journal of Physiology. Renal Physiology·Ivan SabolićHermann Koepsell
Nov 30, 2006·Diabetes·Dervla O'MalleyFiona M Gribble
Jan 16, 2007·Journal of Internal Medicine·E M WrightD F Loo
Aug 28, 2007·The American Journal of Cardiology·James H O'Keefe, David S H Bell
Aug 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Hyeung-Jin JangJosephine M Egan
Aug 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Robert F MargolskeeSoraya P Shirazi-Beechey
May 27, 2008·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Antonio CerielloUNKNOWN Guideline Development Group
Jun 6, 2008·American Journal of Physiology. Cell Physiology·Daniela BalenIvan Sabolic
Dec 2, 2008·Cell Metabolism·Frank ReimannFiona M Gribble
Jun 11, 2009·Cardiovascular Research·Sanjay K BanerjeeFerhaan Ahmad
Oct 8, 2009·American Journal of Physiology. Endocrinology and Metabolism·Ryuichi MoriyaToru Seo
May 27, 2010·The Journal of Clinical Endocrinology and Metabolism·Paul KuoChristopher K Rayner
May 29, 2010·Nature Reviews. Drug Discovery·Edward C Chao, Robert R Henry
Sep 11, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·Paul KuoChristopher K Rayner
Apr 1, 2011·The Proceedings of the Nutrition Society·S P Shirazi-BeecheyM Al-Rammahi
Apr 30, 2011·Physiological Reviews·Ernest M WrightBruce A Hirayama
May 20, 2011·Journal of Anatomy·Flavia MerigoAndrea Sbarbati
Dec 14, 2011·The American Journal of Clinical Nutrition·Tongzhi WuChristopher K Rayner
Apr 28, 2012·The Journal of Pharmacology and Experimental Therapeutics·Toshihide ShibazakiMasayuki Isaji

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Citations

Jan 27, 2016·The Lancet. Diabetes & Endocrinology·Clifford J BaileyAnthony H Barnett
Jul 4, 2015·Experimental Physiology·Hannelore Daniel, Tamara Zietek
Jun 21, 2016·Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery·Gregory BaudFrançois Pattou
Mar 22, 2016·Expert Opinion on Therapeutic Targets·Panai SongVolker Vallon
Mar 24, 2017·Sports Medicine·Asker E Jeukendrup
Nov 3, 2017·JCI Insight·Peter AlmgrenEmma Ahlqvist
Sep 14, 2017·The New England Journal of Medicine·Satish K GargPaul Strumph
Jun 20, 2018·Diabetes Technology & Therapeutics·Thomas DanneOlga Kordonouri
Jun 20, 2018·Diabetes Technology & Therapeutics·Halis Kaan AkturkSatish K Garg
May 26, 2018·Current Opinion in Endocrinology, Diabetes, and Obesity·Halis Kaan AkturkSatish K Garg
May 14, 2019·Diabetes, Obesity & Metabolism·Jessica A Dominguez Rieg, Timo Rieg
May 14, 2019·Diabetes, Obesity & Metabolism·Torben BiesterThomas Danne
Apr 27, 2017·The Journal of Pharmacology and Experimental Therapeutics·David R PowellZhi-Ming Ding
Mar 26, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Anders Lehmann, Pamela J Hornby
Sep 19, 2019·Journal of the Endocrine Society·Dylan D ThomasCaroline M Apovian
Nov 8, 2019·Fundamental & Clinical Pharmacology·Jaspreet KalraArti Dhar
Dec 15, 2019·The Journal of Clinical Endocrinology and Metabolism·David R PowellPablo Lapuerta
Mar 21, 2020·Journal of Diabetes Investigation·Ryuhei SanoTakeshi Ohta
Mar 18, 2020·American Journal of Physiology. Endocrinology and Metabolism·Christoffer MartinussenSten Madsbad
Sep 12, 2017·Diabetes Technology & Therapeutics·Satish K Garg
Apr 2, 2020·Frontiers in Endocrinology·Priska StahelGary F Lewis
Nov 28, 2017·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Leonardo SpatolaSalvatore Badalamenti
Mar 15, 2019·Acta Diabetologica·Nicola SpreghiniMelania Manco
Oct 13, 2017·Physiology·Ernest M WrightDonald D F Loo
Aug 23, 2018·Diabetologia·Timo Rieg, Volker Vallon
Oct 15, 2019·Frontiers in Endocrinology·Belén Pérez-PevidaGema Frühbeck
Aug 24, 2020·Pflügers Archiv : European journal of physiology·Hermann Koepsell

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