Angiotensin-converting enzyme 2 regulates mitochondrial function in pancreatic β-cells

Area of Science:

• * Endocrinology and Metabolism
• * Mitochondrial Biology
• * Molecular Biology

Background:

• * Mitochondrial metabolism is crucial for insulin release and glucose homeostasis.
• * The role of angiotensin-converting enzyme 2 (ACE2) in mitochondrial metabolism is not well understood.
• * ACE2 is known to influence glucose metabolism, but its direct impact on pancreatic beta-cell mitochondrial function requires clarification.

Purpose of the Study:

• * To investigate the regulatory role of ACE2 in mitochondrial function within pancreatic beta-cells.
• * To determine how ACE2 affects glucose-stimulated insulin secretion (GSIS) and mitochondrial parameters.

Main Methods:

• * Utilized INS-1 cells and pancreatic islets from wild-type, Ace2 knockout (Ace2-/-), and db/db mice.
• * Assessed GSIS, mitochondrial membrane potential (MMP), intracellular calcium influx, ATP production, and mitochondrial respiration.
• * Employed PCR array to analyze the expression of mitochondria-related genes.

Main Results:

• * ACE2 overexpression in INS-1 cells restored GSIS and MMP under oxidative stress.
• * ACE2 overexpression upregulated 67 mitochondria-related genes in INS-1 cells.
• * ACE2 ablation in islets decreased GSIS, impaired mitochondrial respiration, reduced ATP production, and decreased expression of genes involved in mitochondrial oxidation.
• * ACE2 overexpression in db/db mouse islets enhanced calcium influx, improved mitochondrial oxidation, and increased GSIS.

Conclusions:

• * ACE2 plays a significant role in regulating mitochondrial function in pancreatic beta-cells.
• * ACE2 influences mitochondrial respiration, ATP production, and gene expression related to mitochondrial oxidation.
• * These findings highlight ACE2 as a potential therapeutic target for improving mitochondrial metabolism and understanding diabetes.