Insulin granule morphology and crinosome formation in mice lacking the pancreatic β cell-specific phogrin (PTPRN2) gene.

Autor: Yasui T; Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan., Mashiko M; Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan., Obi A; Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan., Mori H; Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan., Ito-Murata M; Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan., Hayakawa H; Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan., Kikuchi S; Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan., Hosaka M; Laboratory of Molecular Life Sciences, Department of Biotechnology, Akita Prefectural University, 241-438 Kaidobata-nishi, Nakano Shimoshinjo, Akita, 010-0195, Japan., Kubota C; Center for Food Science and Wellness, Gunma University, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan.; Takasaki University of Health and Welfare, 37-1 Nakaorui, Takasaki, Gunma, 370-0033, Japan., Torii S; Center for Food Science and Wellness, Gunma University, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan., Gomi H; Department of Veterinary Anatomy, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa, 252-0880, Japan. gomi.hiroshi@nihon-u.ac.jp.
Jazyk: angličtina
Zdroj: Histochemistry and cell biology [Histochem Cell Biol] 2024 Mar; Vol. 161 (3), pp. 223-238. Date of Electronic Publication: 2023 Dec 27.
DOI: 10.1007/s00418-023-02256-8
Abstrakt: We recently reported that phogrin, also known as IA-2β or PTPRN2, forms a complex with the insulin receptor in pancreatic β cells upon glucose stimulation and stabilizes insulin receptor substrate 2. In β cells of systemic phogrin gene knockout (IA-2β -/- ) mice, impaired glucose-induced insulin secretion, decreased insulin granule density, and an increase in the number and size of lysosomes have been reported. Since phogrin is expressed not only in β cells but also in various neuroendocrine cells, the precise impact of phogrin expressed in β cells on these cells remains unclear. In this study, we performed a comprehensive analysis of morphological changes in RIP-Cre +/- Phogrin flox/flox (βKO) mice with β cell-specific phogrin gene knockout. Compared to control RIP-Cre +/- Phogrin +/+ (Ctrl) mice, aged βKO mice exhibited a decreased density of insulin granules, which can be categorized into three subtypes. While no differences were observed in the density and size of lysosomes and crinosomes, organelles involved in insulin granule reduction, significant alterations in the regions of lysosomes responding positively to carbohydrate labeling were evident in young βKO mice. These alterations differed from those in Ctrl mice and continued to change with age. These electron microscopic findings suggest that phogrin expression in pancreatic β cells plays a role in insulin granule homeostasis and crinophagy during aging, potentially through insulin autocrine signaling and other mechanisms.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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