Sodium glucose transport modulation in type 2 diabetes and gastric bypass surgery.
Active sodium-glucose transporters play a role to glucose homeostasis and represent novels targets for the management of type 2 diabetes (T2D). Sodium-glucose cotransporter 1 (SGLT1) is essential for intestinal glucose absorption from the lumen into enterocytes, whereas glucose reabsorption by the kidney is mainly mediated by sodium-glucose cotransporter 2 (SGLT2). SGLT2 inhibitors were developed to occlude SGLT2 glucose reabsorption pathway and cause glycosuria, thereby reducing plasma glucose concentrations. This new class of antidiabetic drugs has been shown to be effective in reducing cardiovascular morbidity and mortality in patients with T2D. Initial clinical studies also suggest that SGLT1 inhibition increases glucagon-like peptide 1 (GLP-1) secretion and decreases postchallenge blood glucose excursion, resulting in a dose-dependent improvement of glucose control. In parallel, we recently identified a previously unknown effect of bile diversion in gastric bypass on sodium glucose transport and postprandial glucose homeostasis, through the modulation of intestinal trafficking of endogenous sodium. This mechanism is consistent with available clinical evidence, and opens up new perspectives in metabolic surgery. More generally, the modulation of intestinal sodium-glucose cotransport appears to be a promising avenue to prevent or treat T2D.
Univ. Lille, Inserm, U1190, Translational Research for Diabetes, F-59000, Lille, France; European Genomic Institute for Diabetes, F-59000, Lille, France; CHU Lille, Department of General and Endocrine Surgery, F-59000, Lille, France.
Gregory
G
Baud
Univ. Lille, Inserm, U1190, Translational Research for Diabetes, F-59000, Lille, France; European Genomic Institute for Diabetes, F-59000, Lille, France; CHU Lille, Department of General and Endocrine Surgery, F-59000, Lille, France.
Violeta
V
Raverdy
Univ. Lille, Inserm, U1190, Translational Research for Diabetes, F-59000, Lille, France; European Genomic Institute for Diabetes, F-59000, Lille, France.
Caroline
C
Bonner
Univ. Lille, Inserm, U1190, Translational Research for Diabetes, F-59000, Lille, France; European Genomic Institute for Diabetes, F-59000, Lille, France.
Mehdi
M
Daoudi
Univ. Lille, Inserm, U1190, Translational Research for Diabetes, F-59000, Lille, France; European Genomic Institute for Diabetes, F-59000, Lille, France; CHU Lille, Department of General and Endocrine Surgery, F-59000, Lille, France.
Robert
R
Caiazzo
Univ. Lille, Inserm, U1190, Translational Research for Diabetes, F-59000, Lille, France; European Genomic Institute for Diabetes, F-59000, Lille, France; CHU Lille, Department of General and Endocrine Surgery, F-59000, Lille, France. Electronic address: fpattou@univ-lille2.fr.
François
F
Pattou
D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology / Q000601:surgery*; D015390:Gastric Bypass / Q000379:methods*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D051247:Sodium-Glucose Transport Proteins