title: Pyruvate kinase, muscle isoform 2 promotes proliferation and insulin secretion of pancreatic β-cells via activating Wnt/CTNNB1 signaling.
abstract: Failure of pancreatic β-cells is closely associated with type 2 diabetes mellitus (T2DM), an intractable disease affecting numerous patients. Pyruvate kinase, muscle isoform 2 (PKM2) is a potential modulator of insulin secretion in β-cells. This study aims at revealing roles and possible mechanisms of PKM2 in pancreatic β-cells. Mouse pancreatic β-cell line NIT-1 was used for high glucose treatment and PKM2 overexpression by its specific expression vector. Cell proliferation by Thiazolyl blue assay, cell apoptosis by annexin V-fluorescein isothiocyanate/prodium iodide staining and insulin secretion assay by ELISA were performed in each group. The mRNA and protein levels of related factors were analyzed by real-time quantitative PCR and western blot. Results showed that Pkm2 was inhibited under high glucose conditions compared to the untreated cells (P < 0.01). Its overexpression significantly suppressed NIT-1 cell apoptosis (P < 0.01), and induced cell proliferation (P < 0.05) and insulin secretion (P < 0.05). Related factors showed consistent mRNA expression changes. Protein levels of β-catenin (CTNNB1), insulin receptor substrate 1 (IRS1) and IRS2 were all promoted by PKM2 overexpression (P < 0.01), indicating the activated Wnt/CTNNB1 signaling. These results indicated the inductive roles of PKM2 in pancreatic β-cell NIT-1, including promoting cell proliferation and insulin secretion, and inhibiting cell apoptosis, which might be achieved via activating the Wnt/CTNNB1 signaling and downstream factors. This study offers basic information on the role and mechanism of PKM2 in pancreatic β-cells, and lays the foundation for using PKM2 as a potential therapeutic target in T2DM.
authors.affiliation: Department of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou University Zhengzhou 450003, P. R. China.
authors.forename: Suijun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, P. R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Neonatal Intensive Care Unit, Henan Provincial People's Hospital, Zhengzhou University Zhengzhou 450003, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou University Zhengzhou 450003, P. R. China.
authors.forename: Quanzhong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou University Zhengzhou 450003, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Su
authors.affiliation: Department of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou University Zhengzhou 450003, P. R. China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou University Zhengzhou 450003, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou University Zhengzhou 450003, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Man
authors.affiliation: Department of Endocrinology and Metabolism, Henan Provincial People's Hospital, Zhengzhou University Zhengzhou 450003, P. R. China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D002352:Carrier Proteins; D005947:Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D013963:Thyroid Hormones; D051176:beta Catenin; D000097810:Thyroid Hormone-Binding Proteins; C495267:CTNNB1 protein, mouse; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse
keywords: PKM2; Wnt/CTNNB1; insulin secretion; pancreatic β-cell; type 2 diabetes mellitus
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