PMID- 28605280
OWN - NLM
STAT- MEDLINE
DCOM- 20180430
LR  - 20181217
IS  - 1557-8518 (Electronic)
IS  - 1540-4196 (Linking)
VI  - 15
IP  - 6
DP  - 2017 Aug
TI  - The Gut: A Key to the Pathogenesis of Type 2 Diabetes?
PG  - 259-262
LID - 10.1089/met.2017.0015 [doi]
AB  - In this communication we discuss the role of the gut for the development of type 
      2 diabetes mellitus (T2DM). Gastric emptying rates importantly determine 
      postprandial glucose excursions and regulate postprandial secretion of the 
      incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and 
      glucagon-like peptide-1 (GLP-1). It thereby also determines their powerful, 
      amplifying effect on glucose-induced insulin secretion and thus the ability of 
      the body to regulate glucose disposal. Although disturbances in gastric emptying 
      are not consistent findings in type 2 diabetes, the incretin system is seriously 
      impaired, probably associated with insulin resistance and obesity. Both of the 
      incretin hormones lose (part of) their insulinotropic activity resulting, 
      together with (genetically) defective beta cell function, in the impaired 
      postprandial insulin secretion of T2DM. In addition, glucagon responses are 
      inappropriately increased and importantly contribute to both fasting and 
      postprandial hyperglycemia. This may involve stimulation by GIP, but evidence 
      also points to a role of circulating amino acids, which are elevated due to 
      steatosis-induced impaired glucagon-mediated hepatic clearance, in line with 
      recent work suggesting that the alpha cells and the liver are linked in a close, 
      amino acid-mediated feedback circuit. Thus, the gut plays an important role in 
      the development of T2DM spurred by overeating and defective beta cells.
FAU - Holst, Jens Juul
AU  - Holst JJ
AD  - 1 Department of Biomedical Sciences, Faculty of Health and Medical Sciences, NNF 
      Center for Basic Metabolic Research, University of Copenhagen , Copenhagen, 
      Denmark .
FAU - Pedersen, Jens
AU  - Pedersen J
AD  - 1 Department of Biomedical Sciences, Faculty of Health and Medical Sciences, NNF 
      Center for Basic Metabolic Research, University of Copenhagen , Copenhagen, 
      Denmark .
FAU - Wewer Albrechtsen, Nicolai Jacob
AU  - Wewer Albrechtsen NJ
AD  - 1 Department of Biomedical Sciences, Faculty of Health and Medical Sciences, NNF 
      Center for Basic Metabolic Research, University of Copenhagen , Copenhagen, 
      Denmark .
FAU - Knop, Filip Krag
AU  - Knop FK
AD  - 2 Center for Diabetes Research, Gentofte Hospital, University of Copenhagen , 
      Copenhagen, Denmark .
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170612
PL  - United States
TA  - Metab Syndr Relat Disord
JT  - Metabolic syndrome and related disorders
JID - 101150318
RN  - 0 (Blood Glucose)
RN  - 0 (Incretins)
RN  - 0 (Insulin)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Animals
MH  - Blood Glucose/drug effects/metabolism
MH  - Diabetes Mellitus, Type 2/*etiology
MH  - Gastric Emptying/physiology
MH  - Gastrointestinal Tract/*physiology
MH  - Glucagon/metabolism
MH  - Humans
MH  - Incretins/pharmacology/physiology
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/metabolism
MH  - Intestines/physiology
MH  - Postprandial Period
OTO - NOTNLM
OT  - alpha cells
OT  - amino acids
OT  - glucagon
OT  - glucagon-like peptide-1
OT  - glucose-dependent insulinotropic polypeptide
EDAT- 2017/06/13 06:00
MHDA- 2018/05/01 06:00
CRDT- 2017/06/13 06:00
PHST- 2017/06/13 06:00 [pubmed]
PHST- 2018/05/01 06:00 [medline]
PHST- 2017/06/13 06:00 [entrez]
AID - 10.1089/met.2017.0015 [doi]
PST - ppublish
SO  - Metab Syndr Relat Disord. 2017 Aug;15(6):259-262. doi: 10.1089/met.2017.0015. 
      Epub 2017 Jun 12.