Genetic ablation of p62/SQSTM1 demonstrates little effect on pancreatic β-cell function under autophagy deficiency

• Published in: Biochemical and biophysical research communications Vol. 612; pp. 99 - 104
• Main Authors: Fukae, Toshinaru, Miyatsuka, Takeshi, Himuro, Miwa, Wakabayashi, Yuka, Iida, Hitoshi, Aoyama, Shuhei, Mita, Tomoya, Ikeda, Fuki, Haruna, Hidenori, Takubo, Noriyuki, Nishida, Yuya, Shimizu, Toshiaki, Watada, Hirotaka
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.07.2022
• Subjects: Animals; Atg7; Autophagy; Autophagy-Related Protein 7 - metabolism; Diabetes; Insulin Secretion; Insulin-Secreting Cells - metabolism; Mice; p62/SQSTM1; Sequestosome-1 Protein - genetics; Sequestosome-1 Protein - metabolism; β cell; β cell; p62/SQSTM1; Diabetes; Atg7; Autophagy
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.04.092

Autophagy is known to play an essential role in intracellular quality control through the degradation of damaged organelles and components. We previously demonstrated that β-cell-specific autophagy deficient mice, which lack Atg7, exhibited impaired glucose tolerance, accompanied by the accumulation of sequestosome 1/p62 (hereafter referred to as p62). Whereas p62 has been reported to play essential roles in regulating cellular homeostasis in the liver and adipose tissue, we previously showed that β-cell-specific p62 deficiency does not cause any apparent impairment in glucose metabolism. In the present study, we investigated the roles of p62 in β cells under autophagy-deficient conditions, by simultaneously inactivating both Atg7 and p62 in a β-cell specific manner. Whereas p62 accumulation was substantially reduced in the islets of Atg7 and p62 double-deficient mice, glucose tolerance and insulin secretion were comparable to Atg7 single-deficient mice. Taken together, these findings suggest that the p62 accumulation appears to have little effect on β-cell function under conditions of autophagy inhibition. •Both Atg7 and p62 were ablated simultaneously and specifically in pancreatic β cells in mice.•Whereas p62 accumulation was observed in Atg7 single-deficient islets, there was little accumulation of p62 in Atg7/p62 double-deficient islets.•Autophagy failure by Atg7 deletion cumulatively caused hyperglycemia in both Atg7 single-deficient mice and Atg7/p62 double-deficient mice.•Glucose tolerance and insulin secretion were comparable between Atg7 single-deficient mice and Atg7/p62 double-deficient mice.•The p62 accumulation appears to have little effect on β-cell homeostasis under conditions of autophagy inhibition.