Reversal of increased lymphocyte PC-1 activity in patients with type 2 diabetes treated with metformin.
BACKGROUND
The plasma cell differentiation antigen (PC-1) is an inhibitor of insulin receptor tyrosine kinase activity, and has been implicated in the pathogenesis of insulin resistance in Type 2 diabetes. Metformin increases peripheral insulin sensitivity and, therefore, we have studied the effect of metformin treatment on lymphocyte PC-1 (ecto-alkaline phosphodiesterase I, APD) in patients with Type 2 diabetes.


METHODS
Basal, concanavalin A (Con A)-, and phorbol-12-myristate-13-acetate (PMA)-stimulated lymphocyte PC-1, aminopeptidase N (APN), and dipeptidylpeptidase IV (DPP IV) activities were determined in 16 patients with Type 2 diabetes before and after 3 months of metformin treatment.


RESULTS
Lymphocyte PC-1 in patients with Type 2 diabetes was increased significantly (p<0.001) over control; however, metformin treatment brought its activity in unstimulated and Con A-stimulated lymphocytes to the control level. PMA-stimulated PC-1 in patients with Type 2 diabetes was 17-times higher than in controls, and was reduced to near the control level by 3-month metformin treatment. In Type 2 diabetes, PMA-stimulated ecto-DPP IV was significantly (p<0. 005) increased over control, but was reduced after metformin treatment.


CONCLUSIONS
This study has shown an increased activity of lymphocyte PC-1 in Type 2 diabetes and its reversal by 3-month metformin treatment, corresponding to the improvement of insulin sensitivity. Data obtained are consistent with a role of PC-1 in insulin resistance and suggest a new mechanism of action for metformin via PC-1 inhibition.
Stefanović
V
V
Institute of Nephrology and Hemodialysis, Faculty of Medicine, Nis, Yugoslavia. stefanovic@cent.co.yu
Antić
S
S
Mitic-Zlatković
M
M
Vlahović
P
P
D000328:Adult; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008687:Metformin / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007004:Hypoglycemic Agents; D008562:Membrane Glycoproteins; D003208:Concanavalin A; D008687:Metformin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D013755:Tetradecanoylphorbol Acetate