The renin-angiotensin system as a target to solve the riddle of endocrine pancreas homeostasis

Biomed Pharmacother. 2019 Jan;109:639-645. doi: 10.1016/j.biopha.2018.10.191. Epub 2018 Nov 4.

Abstract

Local renin-angiotensin system (RAS) in the pancreas is linked to the modulation of glucose-stimulated insulin secretion (GSIS) in beta cells and insulin sensitivity in target tissues, emerging as a promising tool in the prevention and/or treatment of obesity, diabetes, and systemic arterial hypertension. Insulin resistance alters pancreatic islet cell distribution and morphology and hypertrophied islets exhibit upregulated angiotensin II type 1 receptor, which drives oxidative stress, apoptosis, and fibrosis, configuring beta cell dysfunction and diminishing islet lifespan. Pharmacological modulation of RAS has shown beneficial effects in diet-induced obesity model, mainly related to the translational potential that angiotensin receptor blockers and ECA2/ANG (1-7)/MAS receptor axis modulation have when it comes to islet preservation and type 2 diabetes prevention and/or treatment. This review describes the existing evidence for different approaches to blocking RAS elements in the management of insulin resistance and diabetes and focuses on islet remodeling and GSIS in rodents and humans.

Keywords: AT1R; GSIS; Islet; Local renin-angiotensin system; Pancreas.

Publication types

  • Review

MeSH terms

  • Angiotensin I / antagonists & inhibitors
  • Angiotensin I / metabolism
  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Animals
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends*
  • Homeostasis / drug effects
  • Homeostasis / physiology*
  • Humans
  • Insulin Resistance / physiology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / metabolism
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • angiotensin I (1-7)