Effects of captopril on glucose metabolism and autophagy in liver and muscle from mice with type 1 diabetes and diet-induced obesity

João Pedro Tôrres Guimarães, Kalhara R. Menikdiwela, Theresa Ramalho, Luiz A.D. Queiroz, Nishan S. Kalupahana, Sonia Jancar, Latha Ramalingam, Joilson O. Martins, Naima Moustaid-Moussa

Research output: Contribution to journalArticlepeer-review

Abstract

Impaired metabolic functions underlie the pathophysiology of diabetes and obesity. The renin-angiotensin system (RAS) is one pathway related to the pathophysiology of both diseases. RAS activation in metabolically active tissues exerts pro-inflammatory effects via angiotensin II (Ang II), linked to dysfunction in cellular processes such as autophagy, which is associated with obesity and diabetes. Here, we determined whether RAS is involved in metabolic dysregulations in a Type 1 Diabetes (T1D) mouse model, treated with captopril, and in an obesity mouse model (Agt-Tg) that overexpresses angiotensinogen (Agt) in adipose tissue. T1D mice had lower plasma leptin, resistin and higher non-esterified fatty acids (NEFA) compared to wild type (Wt) mice, even under captopril treatment. Further, mRNA levels for Agt, At1, Insr, and Beclin1 were upregulated in muscle and liver of T1D mice with captopril compared to Wt. Moreover, autophagy markers LC3 and p62 proteins were decreased, regardless of captopril treatment in the liver from T1D mice. In obese Wt mice, captopril increased muscle Irs1 gene levels. Further, captopril reduced mRNA levels of At1, Insr, Ampk, Beclin1, Atg12, and Lc3 in the liver from both Wt and Agt-Tg mice, while Agt, At1, Insr, and Atg12 expression was reduced in Agt-Tg mice without captopril treatment. Irs1 expression was decreased in the liver from obese Wt mice treated with captopril. Our results suggest that captopril treatment upregulates components of RAS, insulin signaling, and autophagy in both muscle and liver, indicating potential utility of captopril in targeting both insulin sensitivity and autophagy in diabetes and obesity.

Original languageEnglish (US)
Article number166477
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1868
Issue number10
DOIs
StatePublished - Oct 1 2022

Keywords

  • Autophagy
  • Liver
  • Muscle
  • Obesity
  • Renin-angiotensin system
  • Type 1 diabetes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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