title: β-Cell proliferation after a partial pancreatectomy is independent of IRS-2 in mice.
abstract: The glucokinase-induced up-regulation of insulin receptor substrate 2 (IRS-2) plays an important role in β-cell adaptive proliferation in response to high-fat diet-induced insulin resistance. This study aimed to investigate the role of IRS-2 in the proliferation of β-cells after a 60% partial pancreatectomy. IRS-2-deficient (IRS-2(-/-)) mice or wild-type mice were subjected to a pancreatectomy (60% partial pancreatectomy) or a sham operation (Sham). The β-cell proliferation and gene expression profiles of the islets were then assessed. Gene expression in islets from pancreatectomized and Sham C57BL/6J male mice was analyzed using a cDNA microarray analysis. To compare with β-cell proliferation induced by a high-fat diet, Gck(+/-) mice subjected to a pancreatectomy were also analyzed. The IRS-2(-/-) mice exhibited β-cell expansion and a significant increase in β-cell proliferation after the pancreatectomy, compared with the Sham group. Although glucose-stimulated insulin secretion from islets was not impaired, IRS-2(-/-) mice manifested severe hyperglycemia after the pancreatectomy. The expression levels of Aurora kinase B, Cyclin A, and Cyclin B1 in the pancreatectomized islets were also enhanced in the IRS-2(-/-) mice. A gene set enrichment analysis suggested an association between the genes that were up-regulated in the pancreatectomized islets and those involved in M phase progression in the cell cycle. β-Cell proliferation after a pancreatectomy was observed even in the Gck(+/-) mice. In conclusion, IRS-2 was not required for β-cell proliferation but might be needed for functional β-cell mass, after a pancreatectomy. A partial pancreatectomy in mice may be an attractive model for the development of new strategy for exploring the unique nature of β-cell proliferation.
authors: Department of Endocrinology and Metabolism (Y.Tog., J.S., K.O., M.K., E.S., K.T., H.I., A.N., Y.Te.) and Molecular Pharmacology and Neurobiology (Y.G., J.S.), Graduate School of Medicine Yokohama-City University, Yokohama 236-0004, Japan; and Department of Metabolic Medicine (Y.Toc., I.S.), Graduate School of Osaka University, Osaka 565-0871, Japan.
authors: Yu
authors: Y
authors: Togashi
authors: Jun
authors: J
authors: Shirakawa
authors: Kazuki
authors: K
authors: Orime
authors: Mitsuyo
authors: M
authors: Kaji
authors: Eri
authors: E
authors: Sakamoto
authors: Kazuki
authors: K
authors: Tajima
authors: Hideaki
authors: H
authors: Inoue
authors: Akinobu
authors: A
authors: Nakamura
authors: Yoshihiro
authors: Y
authors: Tochino
authors: Yoshio
authors: Y
authors: Goshima
authors: Iichiro
authors: I
authors: Shimomura
authors: Yasuo
authors: Y
authors: Terauchi
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003433:Crosses, Genetic; D056750:Cyclin A1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010180:Pancreatectomy / Q000009:adverse effects*; D012038:Regeneration; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: C503747:Ccna1 protein, mouse; C534700:Ccnb1 protein, mouse; D056750:Cyclin A1; D056744:Cyclin B1; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526298:Irs2 protein, mouse; D005941:Glucokinase; C576924:Aurkb protein, mouse; D064107:Aurora Kinase B