The Gut: A Key to the Pathogenesis of Type 2 Diabetes?

Metab Syndr Relat Disord. 2017 Aug;15(6):259-262. doi: 10.1089/met.2017.0015. Epub 2017 Jun 12.

Abstract

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.

Keywords: alpha cells; amino acids; glucagon; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / etiology*
  • Gastric Emptying / physiology
  • Gastrointestinal Tract / physiology*
  • Glucagon / metabolism
  • Humans
  • Incretins / pharmacology
  • Incretins / physiology
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism
  • Intestines / physiology
  • Postprandial Period

Substances

  • Blood Glucose
  • Incretins
  • Insulin
  • Glucagon