Normal pancreatic β-cell function in mice with RIP-Cre-mediated inactivation of p62/SQSTM1
Akira Honda1, Koji Komiya1, Akemi Hara1,2
1Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Abstract:
Recent studies have suggested that decreased pancreatic β-cell function and mass are common features of patients with type 2 diabetes mellitus. Pancreatic β-cell homeostasis is regulated by various types of signaling molecules and stress responses. Sequestosome 1/p62 (SQSTM1, hereafter referred to as p62) is a ubiquitin-binding adaptor protein involved in cell signaling, oxidative stress, and autophagy. Because p62 appears to play an important role in maintaining mitochondrial quality control, it is possible that the loss of p62 in pancreatic β cells contributes to mitochondrial dysfunction, and thus leading to impaired glucose tolerance. In this study we investigated the physiological roles of p62 by inactivating p62 in a β-cell specific manner. We found that firstly, rat insulin-2 promoter-Cre (RIP-Cre)-mediated p62 inactivation did not cause body weight gain, although ubiquitous inactivation of p62 was previously shown to result in severe obesity. Secondly, we found no gross structural disorganization of the islets of p62-deficient mice. Consistent with normal islet morphology, no impairment in glucose tolerance was observed in mice with RIP-Cre-mediated p62 deletion. These results suggest that p62 is dispensable for normal islet organization and β-cell function.
Insights
Sequestosome 1/p62 (p62) protein is not essential for pancreatic beta-cell function or glucose tolerance. Inactivating p62 in beta cells did not affect body weight, islet structure, or glucose regulation in mice.
Area of Science:
- Cell Biology
- Metabolic Diseases
- Molecular Biology
Background:
- Decreased pancreatic beta-cell function and mass are hallmarks of type 2 diabetes mellitus.
- Pancreatic beta-cell homeostasis relies on signaling molecules and stress responses.
- Sequestosome 1/p62 (p62) is a ubiquitin-binding protein involved in cell signaling, oxidative stress, and autophagy, potentially impacting mitochondrial quality control.
Purpose of the Study:
- To investigate the physiological role of p62 in pancreatic beta cells.
- To determine if p62 deficiency in beta cells contributes to mitochondrial dysfunction and impaired glucose tolerance.
Main Methods:
- Generated mice with beta-cell specific inactivation of p62 using rat insulin-2 promoter-Cre (RIP-Cre) mediated deletion.
- Assessed body weight, islet morphology, and glucose tolerance in p62-deficient mice.
Main Results:
- Beta-cell specific p62 inactivation did not lead to body weight gain, unlike ubiquitous p62 inactivation.
- No gross structural disorganization of pancreatic islets was observed in p62-deficient mice.
- Mice with RIP-Cre-mediated p62 deletion showed normal glucose tolerance.
Conclusions:
- p62 is dispensable for maintaining normal islet organization and beta-cell function.
- The absence of p62 in pancreatic beta cells does not impair glucose tolerance.
- These findings suggest p62 is not critical for beta-cell homeostasis in the context of glucose regulation.
