PMID- 27012770
OWN - NLM
STAT- MEDLINE
DCOM- 20170608
LR  - 20220318
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Linking)
VI  - 310
IP  - 11
DP  - 2016 Jun 1
TI  - Intestinal SGLT1 in metabolic health and disease.
PG  - G887-98
LID - 10.1152/ajpgi.00068.2016 [doi]
AB  - The Na(+)-glucose cotransporter 1 (SGLT1/SLC5A1) is predominantly expressed in 
      the small intestine. It transports glucose and galactose across the apical 
      membrane in a process driven by a Na(+) gradient created by Na(+)-K(+)-ATPase. 
      SGLT2 is the major form found in the kidney, and SGLT2-selective inhibitors are a 
      new class of treatment for type 2 diabetes mellitus (T2DM). Recent data from 
      patients treated with dual SGLT1/2 inhibitors or SGLT2-selective drugs such as 
      canagliflozin (SGLT1 IC50 = 663 nM) warrant evaluation of SGLT1 inhibition for 
      T2DM. SGLT1 activity is highly dynamic, with modulation by multiple mechanisms to 
      ensure maximal uptake of carbohydrates (CHOs). Intestinal SGLT1 inhibition lowers 
      and delays the glucose excursion following CHO ingestion and augments 
      glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion. The latter is 
      likely due to increased glucose exposure of the colonic microbiota and formation 
      of metabolites such as L cell secretagogues. GLP-1 and PYY secretion suppresses 
      food intake, enhances the ileal brake, and has an incretin effect. An increase in 
      colonic microbial production of propionate could contribute to intestinal 
      gluconeogenesis and mediate positive metabolic effects. On the other hand, a 
      threshold of SGLT1 inhibition that could lead to gastrointestinal intolerability 
      is unclear. Altered Na(+) homeostasis and increased colonic CHO may result in 
      diarrhea and adverse gastrointestinal effects. This review considers the 
      potential mechanisms contributing to positive metabolic and negative intestinal 
      effects. Compounds that inhibit SGLT1 must balance the modulation of these 
      mechanisms to achieve therapeutic efficacy for metabolic diseases.
CI  - Copyright (c) 2016 the American Physiological Society.
FAU - Lehmann, Anders
AU  - Lehmann A
AD  - Division of Endocrinology, Department of Physiology, Institute of Neuroscience 
      and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, 
      Sweden; and.
FAU - Hornby, Pamela J
AU  - Hornby PJ
AD  - Cardiovascular and Metabolic Disease, Janssen Research and Development, LLC, 
      Spring House, Pennsylvania phornby@its.jnj.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160324
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (SLC5A1 protein, human)
RN  - 0 (Sodium-Glucose Transporter 1)
SB  - IM
MH  - Animals
MH  - Enteroendocrine Cells/metabolism
MH  - Gastrointestinal Motility
MH  - Humans
MH  - Intestinal Absorption
MH  - Intestinal Mucosa/*metabolism
MH  - Metabolic Diseases/drug therapy/genetics/*metabolism/microbiology
MH  - Sodium-Glucose Transporter 1/antagonists & inhibitors/genetics/*metabolism
OTO - NOTNLM
OT  - SLC5A1
OT  - diarrhea
OT  - gluconeogenesis
OT  - glucose tolerance
OT  - ileal brake
OT  - incretin
OT  - microbiome
OT  - monosaccharide
OT  - sodium/hydrogen exchanger isoform 3
OT  - taste receptors
EDAT- 2016/03/26 06:00
MHDA- 2017/06/09 06:00
CRDT- 2016/03/26 06:00
PHST- 2016/02/15 00:00 [received]
PHST- 2016/03/21 00:00 [accepted]
PHST- 2016/03/26 06:00 [entrez]
PHST- 2016/03/26 06:00 [pubmed]
PHST- 2017/06/09 06:00 [medline]
AID - ajpgi.00068.2016 [pii]
AID - 10.1152/ajpgi.00068.2016 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2016 Jun 1;310(11):G887-98. doi: 
      10.1152/ajpgi.00068.2016. Epub 2016 Mar 24.