title: Overcoming Insulin Insufficiency by Forced Follistatin Expression in β-cells of db/db Mice.
abstract: Diabetes poses a substantial burden to society as it can lead to serious complications and premature death. The number of cases continues to increase worldwide. Two major causes of diabetes are insulin resistance and insulin insufficiency. Currently, there are few antidiabetic drugs available that can preserve or protect β-cell function to overcome insulin insufficiency in diabetes. We describe a therapeutic strategy to preserve β-cell function by overexpression of follistatin (FST) using an AAV vector (AAV8-Ins-FST) in diabetic mouse model. Overexpression of FST in the pancreas of db/db mouse increased β-cell islet mass, decreased fasting glucose level, alleviated diabetic symptoms, and essentially doubled lifespan of the treated mice. The observed islet enlargement was attributed to β-cell proliferation as a result of bioneutralization of myostatin and activin by FST. Overall, our study indicates overexpression of FST in the diabetic pancreas preserves β-cell function by promoting β-cell proliferation, opening up a new therapeutic avenue for the treatment of diabetes.
authors: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA; Cardiovascular Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Chunxia
authors: C
authors: Zhao
authors: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
authors: Chunping
authors: C
authors: Qiao
authors: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
authors: Ru-Hang
authors: RH
authors: Tang
authors: Cardiovascular Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Jiangang
authors: J
authors: Jiang
authors: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
authors: Jianbin
authors: J
authors: Li
authors: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
authors: Carrie Bette
authors: CB
authors: Martin
authors: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
authors: Karen
authors: K
authors: Bulaklak
authors: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
authors: Juan
authors: J
authors: Li
authors: Cardiovascular Division of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors: Dao Wen
authors: DW
authors: Wang
authors: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA. Electronic address: xxiao@email.unc.edu.
authors: Xiao
authors: X
authors: Xiao
mesh_terms: D000818:Animals; D015415:Biomarkers; D049109:Cell Proliferation; D000229:Dependovirus / Q000145:classification / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D038681:Follistatin / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D065288:Serogroup; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D015415:Biomarkers; D038681:Follistatin; D007328:Insulin; D008024:Ligands; D051785:Smad Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt