Timp-1 Transgenic Mice Recover from Diabetes Induced by Multiple Low-dose Streptozotocin.
From: Department of Nephrology, Kidney Center and Key Lab of People’s Liberation Army, General Hospital of PLA, Fuxing Road 28, Beijing 100853, PR China.
Diabetes
- Publish Date: Jan 2007
- ISSN: 0012-1797
- Volume: 56
- Issue: 1
- Pages: 49-56
- Medium: Print
- Language: English
- Citation (JAMA): Jiang Hongwei, Zhu Hanyu, Chen Xiangmei, et al. Timp-1 Transgenic Mice Recover from Diabetes Induced by Multiple Low-dose Streptozotocin.. Diabetes Jan 2007;56:49-56
Abstract
Type 1 diabetes results from autoimmune destruction of the insulin-producing beta-cells of pancreatic islets, of which the capacity for self-replication in the adult is too limited to restore following extensive tissue injury. Tissue inhibitor of metalloproteinase (TIMP)-1 inhibits matrix metalloproteinase activity and regulates proliferation and apoptosis of a variety of cells types, depending on the context. Here, we show that overexpression of human TIMP-1 in pancreatic beta-cells of transgenic mice counteracts the cytotoxicity and insulitis induced by multiple low-dose streptozotocin (MLDS). Nontransgenic mice developed severe hyperglycemia, hypoinsulinemia, and insulitis 2 weeks after streptozotocin administration and died within 17 weeks. However, MLDS-treated transgenic mice gradually normalized the metabolic parameters and survived. beta-Cell mass increased in parallel as a result of enhancement of beta-cell replication. Thus, our results have demonstrated for the first time that overexpression of TIMP-1 in beta-cells enhances the replication of pancreatic islets beta-cells and counteracts type 1 diabetes, indicating that the TIMP-1 gene may be a potential target to prevent, or even reverse, type 1 diabetes.
Mesh Headings (Keywords): Animals, Blood Glucose, Crosses, Genetic, Diabetes Mellitus, Experimental, Humans, Insulin, Insulin-Secreting Cells, Mice, Mice, Transgenic, RNA, Messenger, Remission, Spontaneous, Tissue Inhibitor of Metalloproteinase-1
Check for Full Text / PubMed Unique Identifier (PMID): 17192464
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