The Gut: A Key to the Pathogenesis of Type 2 Diabetes?
Research output: Contribution to journal › Review › Research › peer-review
Standard
The Gut : A Key to the Pathogenesis of Type 2 Diabetes? / Holst, Jens Juul; Pedersen, Jens; Wewer Albrechtsen, Nicolai Jacob; Knop, Filip Krag.
In: Metabolic Syndrome and Related Disorders, Vol. 15, No. 6, 08.2017, p. 259-262.Research output: Contribution to journal › Review › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - The Gut
T2 - A Key to the Pathogenesis of Type 2 Diabetes?
AU - Holst, Jens Juul
AU - Pedersen, Jens
AU - Wewer Albrechtsen, Nicolai Jacob
AU - Knop, Filip Krag
PY - 2017/8
Y1 - 2017/8
N2 - 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.
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.
KW - Journal Article
U2 - 10.1089/met.2017.0015
DO - 10.1089/met.2017.0015
M3 - Review
C2 - 28605280
VL - 15
SP - 259
EP - 262
JO - Metabolic Syndrome and Related Disorders
JF - Metabolic Syndrome and Related Disorders
SN - 1540-4196
IS - 6
ER -
ID: 182933671