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.
| Language | English (US) |
|---|---|
| Pages | 866-874 |
| Number of pages | 9 |
| Journal | Molecular Therapy |
| Volume | 23 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jan 1 2015 |
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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, 01.01.2015, p. 866-874.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overcoming insulin insufficiency by forced follistatin expression in β-cells of db/db mice
AU - Zhao,Chunxia
AU - Qiao,Chunping
AU - Tang,Ru Hang
AU - Jiang,Jiangang
AU - Li,Jianbin
AU - Martin,Carrie Bette
AU - Bulaklak,Karen
AU - Li,Juan
AU - Wang,Dao Wen
AU - Xiao,Xiao
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
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U2 - 10.1038/mt.2015.29
DO - 10.1038/mt.2015.29
M3 - Article
VL - 23
SP - 866
EP - 874
JO - Molecular Therapy
T2 - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 5
ER -