Reduced peroxisomal function increases insulin secretion, promotes insulin oxidation, and impairs β cell maturity

Area of Science:

• Cell Biology
• Metabolism
• Endocrinology

Background:

• Peroxisomes are crucial organelles involved in lipid metabolism and redox homeostasis.
• Their role in maintaining pancreatic beta cell function and identity is largely unexplored.

Purpose of the Study:

• To investigate the impact of peroxisomal dysfunction on pancreatic beta cell function and glucose homeostasis.
• To determine if peroxisomal activity is essential for maintaining beta cell identity and maturity.

Main Methods:

• Utilized Pex5 deletion mouse models to induce tissue-specific peroxisome deficiency.
• Assessed glucose-stimulated insulin secretion (GSIS), oxidative stress markers, and beta cell maturity markers.
• Employed ion mobility mass spectrometry to analyze insulin protein oxidation and degradation products.

Main Results:

• Peroxisome deficiency in male mice led to elevated GSIS and glucose intolerance.
• Observed oxidation of insulin proteins and truncated insulin peptides in islets.
• Increased markers of oxidative stress, including altered metabolite profiles, lipid peroxidation, and protein carbonylation.

Conclusions:

• Peroxisome dysfunction compromises glucose homeostasis by promoting insulin oxidation and degradation.
• Loss of peroxisomes reduces markers of beta cell maturity, impacting overall beta cell function.
• Peroxisomes are identified as key regulators of glucose homeostasis and beta cell maintenance.