Related Experiment Video
Updated: Jul 8, 2025
Quantification of Diabetes-induced Adherent Leukocytes in Retinal Vasculature
Published on: January 24, 2025
The role of captopril in leukotriene deficient type 1 diabetic mice
João Pedro Tôrres Guimarães1,2,3, Luiz A D Queiroz1, Kalhara R Menikdiwela2,4
1Laboratory of Immunoendocrinology, School of Pharmaceutical Sciences, Department of Clinical and Toxicological Analyses, University of São Paulo, São Paulo, SP, Brazil.
Abstract:
T1D can be associated with metabolic disorders and several impaired pathways, including insulin signaling, and development of insulin resistance through the renin-angiotensin system (RAS). The main precursor of RAS is angiotensinogen (Agt) and this system is often linked to autophagy dysregulation. Dysregulated autophagy has been described in T1D and linked to impairments in both glucose metabolism, and leukotrienes (LTs) production. Here, we have investigated the role of RAS and LTs in both muscle and liver from T1D mice, and its effects on insulin and autophagy pathways. We have chemically induced T1D in 129sve and 129sve 5LO-/- mice (lacking LTs) with streptozotocin (STZ). To further inhibit ACE activity, mice were treated with captopril (Cap). In muscle of T1D mice, treatment with Cap increased the expression of RAS (angiotensinogen and angiotensin II receptor), insulin signaling, and autophagy markers, regardless of the genotype. In the liver of T1D mice, the treatment with Cap increased the expression of RAS and insulin signaling markers, mostly when LTs were absent. 5LO-/- T1D mice showed increased insulin sensitivity, and decreased NEFA, after the Cap treatment. Cap treatment impacted both insulin signaling and autophagy pathways at the mRNA levels in muscle and liver, indicating the potential role of ACE inhibition on insulin sensitivity and autophagy in T1D.
Insights
Captopril treatment improved insulin signaling and autophagy in type 1 diabetes (T1D) mouse models, suggesting ACE inhibition benefits metabolic pathways. This research highlights potential therapeutic strategies for T1D complications.
Area of Science:
- Metabolic disorders
- Endocrinology
- Molecular biology
Background:
- Type 1 diabetes (T1D) is linked to metabolic dysfunction, impaired insulin signaling, and insulin resistance.
- The renin-angiotensin system (RAS) and leukotrienes (LTs) are implicated in T1D, affecting autophagy and glucose metabolism.
- Autophagy dysregulation is observed in T1D, impacting glucose and LT production.
Purpose of the Study:
- To investigate the roles of RAS and LTs in muscle and liver of T1D mice.
- To determine the effects of RAS and LTs on insulin and autophagy pathways in T1D.
- To evaluate the impact of ACE inhibition via captopril on these pathways.
Main Methods:
- Type 1 diabetes was induced using streptozotocin (STZ) in 129sve and 129sve 5LO-/- mice (lacking LTs).
- Mice were treated with captopril (Cap) to inhibit ACE activity.
- Gene expression of RAS components, insulin signaling, and autophagy markers were analyzed in muscle and liver tissues.
Main Results:
- Captopril treatment increased RAS, insulin signaling, and autophagy markers in the muscle of T1D mice.
- In the liver, captopril enhanced RAS and insulin signaling, particularly in the absence of LTs (5LO-/- mice).
- 5LO-/- T1D mice showed improved insulin sensitivity and reduced NEFA levels after captopril treatment.
Conclusions:
- ACE inhibition with captopril positively impacts insulin signaling and autophagy pathways in T1D mouse models.
- The findings suggest a potential therapeutic role for ACE inhibitors in managing insulin sensitivity and autophagy in T1D.
- Leukotrienes may modulate the effects of ACE inhibition on metabolic pathways in T1D.
