Overcoming insulin insufficiency by forced follistatin expression in β-cells of db/db mice

Chunxia Zhao, Chunping Qiao, Ru Hang Tang, Jiangang Jiang, Jianbin Li, Carrie Bette Martin, Karen Bulaklak, Juan Li, Dao Wen Wang, Xiao Xiao

Research output: Contribution to journalArticle

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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.

LanguageEnglish (US)
Pages866-874
Number of pages9
JournalMolecular Therapy
Volume23
Issue number5
DOIs
StatePublished - May 9 2015

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Follistatin
Insulin
Pancreas
Cell Proliferation
Myostatin
Activins
Premature Mortality
Islets of Langerhans
Hypoglycemic Agents
Insulin Resistance
Fasting
Glucose
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Overcoming insulin insufficiency by forced follistatin expression in β-cells of db/db mice. / Zhao, Chunxia; Qiao, Chunping; Tang, Ru Hang; Jiang, Jiangang; Li, Jianbin; Martin, Carrie Bette; Bulaklak, Karen; Li, Juan; Wang, Dao Wen; Xiao, Xiao.

In: Molecular Therapy, Vol. 23, No. 5, 09.05.2015, p. 866-874.

Research output: Contribution to journalArticle

Zhao, C, Qiao, C, Tang, RH, Jiang, J, Li, J, Martin, CB, Bulaklak, K, Li, J, Wang, DW & Xiao, X 2015, 'Overcoming insulin insufficiency by forced follistatin expression in β-cells of db/db mice' Molecular Therapy, vol. 23, no. 5, pp. 866-874. DOI: 10.1038/mt.2015.29
Zhao C, Qiao C, Tang RH, Jiang J, Li J, Martin CB et al. Overcoming insulin insufficiency by forced follistatin expression in β-cells of db/db mice. Molecular Therapy. 2015 May 9;23(5):866-874. Available from, DOI: 10.1038/mt.2015.29
Zhao, Chunxia ; Qiao, Chunping ; Tang, Ru Hang ; Jiang, Jiangang ; Li, Jianbin ; Martin, Carrie Bette ; Bulaklak, Karen ; Li, Juan ; Wang, Dao Wen ; Xiao, Xiao. / Overcoming insulin insufficiency by forced follistatin expression in β-cells of db/db mice. In: Molecular Therapy. 2015 ; Vol. 23, No. 5. pp. 866-874
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