[The effect of metformin on insulin receptor protein tyrosine kinase activity of HIT-T15 cell exposed to high concentration glucose and free fatty acid].
OBJECTIVE
To study the effect of metformin on insulin receptor (IRc) protein tyrosine kinase (PTK) activity of HIT-T15 cell exposed to high glucose and free fatty acid (FFA) concentration, and to explore the mechanism of metformin (MF) improving beta cell insulin resistance.


METHODS
HIT-T15 cells were incubated for 48 h in a medium containing 5.5-16.7 mmol/L glucose and 0.5 mmol/L palmitic acid respectively. The cells were re-incubated for another 24 h with or without 2.5 microg/mL MF. The PTK activities of IRc were measured by radioactive enzyme assay.


RESULTS
The enzymatic activities of IRc PTK were significantly decreased to HIT-T15 cells having the exposure to high glucose or high FFA concentration, when compared to control [(52.5 +/- 18.6) or (54.6 +/- 14.0) vs. (119.4 +/- 29.1) pmol/(min x microg), P < 0.01 respectively. The enzymatic activities of IRc PTK in HIT-T15 cells reincubated with 2.5 microg/mL MF for an additional 24 h were significantly increased vs MF free group [(113.0 +/- 29.8) vs. (52.5 +/- 18.6) pmol/(min x microg), x 98.6 +/- 26.1) vs. (54.6 +/- 14.0) pmol/(min x microg), P < 0.01 respectively], and were no significant difference in comparison with control group (P > 0.05).


CONCLUSIONS
The enzymatic activities of IRc PTK are significantly decreased in HIT-T15 cells chronically exposed to elevated glucose or free fatty acids levels. Metformin can restore approximately normal enzymatic activities of PTK of HIT-T15 cells, of which the PTK activities have been impaired by chronic exposure to high glucose or free fatty acids levels.
Wang
Yu
Y
Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China.
Li
Xiu-jun
XJ
Zhang
Min
M
Wu
Yun-hong
YH
Tong
Nan-wei
NW
Zhao
Tie-yun
TY
Li
Jie
J
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology; D008687:Metformin / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D008687:Metformin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose