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  • Title: Regenerative and therapeutic effects of heparin-binding epidermal growth factor-like growth factor on diabetes by gene transduction through retrograde pancreatic duct injection of adenovirus vector.
    Author: Kozawa J, Tokui Y, Moriwaki M, Li M, Ohmoto H, Yuan M, Zhang J, Iwahashi H, Imagawa A, Yamagata K, Tochino Y, Shimomura I, Higashiyama S, Miyagawa J.
    Journal: Pancreas; 2005 Jul; 31(1):32-42. PubMed ID: 15968245.
    Abstract:
    OBJECTIVES: In the adult pancreas, pre-existing beta cells, stem cells, and endocrine progenitor cells residing in the duct lining are considered important sources for beta-cell regeneration. A member of the epidermal growth factor (EGF) family, heparin binding (HB)-EGF, may promote this process. We examined whether HB-EGF gene transduction into duct cells could promote beta-cell regeneration. METHODS: We administered an HB-EGF adenovirus vector construct to male Institute of Cancer Research mice by retrograde injection through the pancreatic duct. We also performed HB-EGF gene transduction into cultured duct cells. RESULTS: On immunohistochemical and histomorphometric analysis of the experimental group, insulin-positive cells differentiated from duct cells, and the 5-bromo-2-deoxyuridine labeling index of beta cells was significantly increased. beta-cell mass was also increased, and the glucose tolerance of diabetic mice was improved at 12 weeks after injection. Using cultured pancreatic duct cells, we confirmed that HB-EGF gene transduction induced both insulin gene expression and insulin production by these cells. CONCLUSIONS: These results indicate that HB-EGF gene transduction into adult pancreatic duct cells not only promotes the proliferation of pre-existing beta cells but also leads to beta-cell differentiation from duct cells, and the resulting increase in beta-cell mass improves glucose tolerance.
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