Reversal of increased lymphocyte PC-1 activity in patients with Type 2 diabetes treated with metformin

✍ Scribed by Vladisav Stefanović; Slobodan Antić; Marina Mitić-Zlatković; Predrag Vlahović

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 76 KB
• Volume: 15
• Category: Article
• ISSN: 1520-7552
• DOI: 10.1002/(sici)1520-7560(199911/12)15:6<400::aid-dmrr66>3.0.co;2-4

✦ Synopsis

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.

Conclusion:

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.