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Advanced glycation end products downregulate glucokinase in mice
Author(s) -
Jung Hongsoo,
Joo Jindeok,
Jeon Yeonsu,
Lee Junga,
In Janghyeok,
Kim Daewoo,
Kang Eujin,
Kim Yongshin,
Lim Yonggul,
Kang Jaehyeok,
Choi Jinwoo
Publication year - 2011
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.1208
Subject(s) - glucokinase , medicine , endocrinology , islet , glycation , carbohydrate metabolism , diabetes mellitus , chemistry , insulin , metabolism , biology
Background Glucokinase, the enzyme that catalyses the conversion of glucose to G‐6‐P, plays a key role in glucose metabolism. AGEs are implicated in diabetic complications. A previous study reported that AGEs decreased β‐cell function through inhibition of cytochrome c oxidase and adenosine triphosphate synthesis. This study investigated the effects of AGEs on glucokinase and islet function. Methods Six‐month‐old male C57BL6 mice were divided into bovine serum albumin (BSA) and AGE‐BSA groups. BSA (200 µg/g) and AGE‐BSA (60 U/g) were administered intraperitoneally twice daily. After 2 weeks, serum AGE levels were measured, oral glucose tolerance test was performed, and insulin levels during the oral glucose tolerance test were determined. Glucokinase protein expression level and activity were measured in pancreatic islets. Results We observed that the normal mice (C57/BL6) treated for 2 weeks with AGE‐BSA showed impaired glucose tolerance and decrease in acute insulin release. Glucokinase activity in islets from the AGE‐BSA‐treated mice was significantly inhibited and accompanied by blunted response of islets to high glucose stimulation. Moreover, in vitro experiments showed that glucokinase protein expression was decreased, its activity was inhibited, and islet function was decreased. GKA partially restored glucokinase activity and islet function caused by AGEs. Conclusions We concluded that AGEs inhibited glucokinase activity, leading to islet dysfunction in mouse pancreatic islets. Copyright © 2011 John Wiley & Sons, Ltd.