Daijiworld Media Network - Baton Rouge
Baton Rouge, Aug 29: Researchers at LSU's Pennington Biomedical Research Center have identified an important role played by tiny structures inside cells called peroxisomes in protecting insulin and maintaining the health and maturity of insulin-producing pancreatic beta cells.
The study, published in JCI Insight, found that disrupting peroxisomal function in animal models triggered oxidative stress, chemically altered insulin and reduced markers associated with mature, normally functioning beta cells.
Peroxisomes help cells process fats, remove harmful substances and maintain the balance between reactive oxygen species and antioxidant defenses. While their importance in cellular metabolism has been established, their specific role in pancreatic beta cell function and maturity has been less understood.
Researchers genetically modified animal models to delete the Pex5 gene, which is essential for normal peroxisomal function, specifically in pancreatic cells or insulin-producing beta cells. They then assessed glucose tolerance, insulin secretion, oxidative stress, metabolism and markers of beta cell maturity.
Animals with impaired peroxisomal function developed glucose intolerance early in life despite their beta cells releasing more insulin in response to sugar. Researchers found that some of the secreted insulin had undergone oxidation, indicating chemical changes associated with oxidative stress.
Using advanced mass spectrometry, the team identified oxidized insulin proteins as well as a truncated insulin-derived peptide in animals with peroxisomal deficiency.
The findings suggest that increased insulin secretion alone may not be sufficient to maintain normal blood sugar control. The integrity of insulin and the health of the beta cells producing it also appear to be critical.
"Beta cells are highly sensitive to changes in their metabolic environment. Our findings indicate an important role for peroxisomes to help beta cells manage a healthy environment, protect insulin from damage and maintain a mature identity," said Dr Jason Collier, Director of the Islet Biology and Inflammation Laboratory at Pennington Biomedical.
Researchers also found that impaired peroxisomal function reduced markers associated with mature beta cell identity, suggesting that these structures may help beta cells retain the specialised characteristics required for normal insulin production and release.
The effects differed between male and female animal models. Male animals developed a more pronounced metabolic response, including glucose intolerance and increased insulin secretion, while females showed a milder metabolic effect. However, both sexes showed evidence of reduced beta cell maturity.
The findings provide new insight into the relationship between cellular metabolism, oxidative stress, insulin integrity and beta cell health, according to Dr Susan Burke, Director of the Immunogenetics Laboratory.
"Additional research will be needed to determine whether impaired peroxisomal function contributes to beta cell dysfunction in people with obesity, prediabetes, diabetes or other metabolic diseases," Burke said.
The study involved researchers from Pennington Biomedical, The University of Tennessee, Vanderbilt University Medical Center and The University of Alabama at Birmingham. The research was supported by the National Institutes of Health through a P20 award to Burke.