title: Maternal Low Protein Isocaloric Diet Suppresses Pancreatic β-Cell Proliferation in Mouse Offspring via miR-15b.
abstract: The mechanism underlying the increased susceptibility of type 2 diabetes in offspring of maternal malnutrition is poorly determined. Here we tested the hypothesis that functional microRNAs (miRNAs) mediated the maternal low-protein (LP) isocaloric diet induced pancreatic β-cell impairment. We performed miRNA profiling in the islets from offspring of LP and control diet mothers to explore the potential functional miRNAs responsible for β-cell dysfunction. We found that LP offspring exhibited impaired glucose tolerance due to decreased β-cell mass and insulin secretion. Reduction in the β-cell proliferation rate and cell size contributed to the decreased β-cell mass. MiR-15b was up-regulated in the islets of LP offspring. The up-regulated miR-15b inhibited pancreatic β-cell proliferation via targeting cyclin D1 and cyclin D2. Inhibition of miR-15b in LP islet cells restored β-cell proliferation and insulin secretion. Our findings demonstrate that miR-15b is critical for the regulation of pancreatic β-cells in offspring of maternal protein restriction, which may provide a further insight for β-cell exhaustion originated from intrauterine growth restriction.
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Su
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Song
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic Diseases (Y.S., X.J., Y.L., F.L., Y.P., D.S., J.H., G.N., Y.C., W.W.), Shanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (Y.C., G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism; D056742:Cyclin D2 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D018753:Diet, Protein-Restricted; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism
chemical_list: D056742:Cyclin D2; D007328:Insulin; D035683:MicroRNAs; C570833:Mirn15 microRNA, mouse; D019938:Cyclin D1