Metformin normalizes type 2 diabetes-induced decrease in cell proliferation and neuroblast differentiation in the rat dentate gyrus.
In this study, we observed the effects of metformin, one of the most widely prescribed drugs for the treatment of type 2 diabetes, on cell proliferation and neuroblast differentiation in the subgranular zone of the hippocampal dentate gyrus (SZDG) in Zucker diabetic fatty (ZDF) rats, which are a model for type 2 diabetes. For this, metformin was administered orally once a day to 14-week-old ZDF rats for 2 weeks and the animals were sacrificed at 16 weeks of age. During this period, blood glucose levels were higher in the vehicle-treated ZDF rats than in the Zucker lean control (ZLC) rats. Metformin treatment significantly decreased the blood glucose levels from 15.5 weeks of age. In the SZDG, Ki67 (a marker for cell proliferation)- and doublecortin (DCX, a marker for differentiated neuroblasts)-immunoreactive cells were much lower in the vehicle-treated ZDF rats than in the ZLC rats. In the metformin-treated ZDF group, Ki67- and DCX-immunoreactive cells were significantly increased in the SZDG compared to those in the vehicle-treated ZDF group. These results suggest that diabetes significantly reduces cell proliferation and neuroblast differentiation in the SZDG and that metformin treatment normalizes the reduction of cell proliferation and neuroblast differentiation in the SZDG in diabetic rats.
Hwang
In Koo
IK
Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
Kim
Il Yong
IY
Joo
Eun Jung
EJ
Shin
Jae Hoon
JH
Choi
Ji Won
JW
Won
Moo-Ho
MH
Yoon
Yeo Sung
YS
Seong
Je Kyung
JK
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D000089662:Doublecortin Protein; D005260:Female; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011924:Rats, Zucker
D001786:Blood Glucose; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008687:Metformin