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

Francielle Graus-Nunes1, Vanessa Souza-Mello1

  • 1Laboratory of Morphometry, Metabolism, and Cardiovascular Diseases, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Brazil.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|November 8, 2018
PubMed

Insights

The pancreatic renin-angiotensin system (RAS) influences insulin secretion and sensitivity. Blocking RAS components shows promise for treating obesity, diabetes, and hypertension by preserving pancreatic islet cells.

Area of Science:

  • Endocrinology and Metabolism
  • Cardiovascular Physiology
  • Cell Biology

Background:

  • The local renin-angiotensin system (RAS) in the pancreas plays a crucial role in regulating glucose-stimulated insulin secretion (GSIS) and insulin sensitivity.
  • Insulin resistance is associated with pancreatic islet cell alterations, including upregulated angiotensin II type 1 receptor (AT1R) in hypertrophied islets, leading to oxidative stress, apoptosis, and fibrosis.
  • These changes contribute to beta-cell dysfunction and reduced islet lifespan, impacting overall metabolic health.

Purpose of the Study:

  • To review the evidence for blocking RAS elements in managing insulin resistance and diabetes.
  • To focus on the impact of RAS modulation on islet remodeling and GSIS in both rodent and human studies.
  • To highlight the therapeutic potential of RAS inhibition for obesity, diabetes, and hypertension.

Main Methods:

  • Literature review of existing evidence on pharmacological modulation of the RAS.
  • Analysis of studies investigating angiotensin receptor blockers (ARBs) and the ACE2/ANG (1-7)/MAS receptor axis.
  • Examination of data from rodent models of diet-induced obesity and studies in human subjects.

Main Results:

  • Pharmacological RAS modulation demonstrates beneficial effects in preclinical models of obesity.
  • Angiotensin receptor blockers and modulation of the ACE2/ANG (1-7)/MAS receptor axis show potential for islet preservation.
  • These interventions are associated with the prevention and treatment of type 2 diabetes.

Conclusions:

  • The local pancreatic RAS is a significant factor in beta-cell function and insulin resistance.
  • Targeting RAS components offers a promising therapeutic strategy for metabolic disorders.
  • Further research into RAS modulation is warranted for effective islet preservation and type 2 diabetes management.
Keywords:
AT1RGSISIsletLocal renin-angiotensin systemPancreas

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