Access Type

Open Access Thesis

Date of Award

January 2015

Degree Type

Thesis

Degree Name

M.S.

Department

Pharmaceutical Sciences

First Advisor

ZHENGPING YI

Abstract

Metformin is a drug from the biguanide class and it has been in use for the treatment of type 2 diabetes for a long time, and it can improve insulin sensitivity in skeletal muscle. However, the mechanism for metformin’s action is unclear. Phosphatases and kinases, and their subunits are the proteins required for dephosphorylation and phosphorylation of proteins in cells during various signaling pathways. Phosphorylation studies of proteins from primary cell culture derived from skeletal muscle tissue from obese/overweight insulin resistant participants will help to understand the regulation of phosphorylation in phosphatases and kinases by metformin.

In the current research, we used primary cell culture cells of human skeletal muscle tissue to identify and quantify the phosphorylation effects of metformin in obese/overweight participants. After treating cells with different conditions which include different concentration of metformin, we identify 2930 phospho sites in 1085 proteins. Among 2930 phospho sites, 325 phospho sites showed significant change among 6 sets of samples (total 24 samples). Of particular interest, metformin treatment significantly changed phosphorylation levels of 23 sites including 6 phosphorylation sites in 4 phosphatase subunits and 17 phosphorylation sites in 9 kinases/kinase subunits. These results provide new information on how metformin works in skeletal muscle cells.

Download

Share

COinS