Vol. 10, No 1, 2003 pp. 27 - 30
UC 616.379-008.64:616-085 
PROLONGED SULFONYLUREA TREATMENT HAS NO EFFECT
ON LYMPHOCYTE PC-1 EXPRESSION IN PATIENTS
WITH TYPE 2 DIABETES MELLITUS
Slobodan Antić1, Predrag Vlahović2, Maja Milojković3,
Marina Mitić-Zlatković2, Milena Golubović1, Vladisav Stefanović2
1Clinic of Endocrinology, Clinical Centre, Faculty of Medicine, Niš
2Institute of Nephrology and Hemodialysis, Clinical Centre, Faculty of Medicine, Niš
3Institute of Pathophysiology, Faculty of Medicine, Niš, Serbia
Summary. Plasma cell antigen (PC-1) is an inhibitor of insulin receptor tyrosine kinase, which plays an important role in insulin resistance pathogenesis in type 2 diabetes mellitus, obesity and some other insulin resistant states. In a recent study we have demonstrated an increased lymphocyte PC-1 activity in patients with type 2 diabetes and its reversal by 3-month metformin treatment, corresponding to the improvement of insulin sensitivity. The aim of this study was to investigate the effect of prolonged treatment with two commonly used sulfonylurea agents, gliclazide and glibenclamide, on lymphocyte PC-1 expression.
Twenty-six newly diagnosed, obese type 2 diabetes patients with a body mass index >30, and 14 healthy controls were enrolled in the study. Basal, concanavalin A (Con A)-stimulated, and phorbol-12-myristate-13-acetate (PMA)-stimulated lymphocyte PC-1 was determined in 26 diabetic patients before and after 3-month of gliclazide (12 patients) and glibenclamide (14 patients) treatment.
Fasting plasma glucose and blood fructosamine decreased significantly after treatment. Pre-treatment lymphocyte PC-1 activity in diabetic patients was significantly higher than in controls. Treatment with gliclazide or glibenclamide did not produced any significant effect in unstimulated, Con A-stimulated or PMA-stimulated PC-1 activity.
In conclusion, this study has confirmed an increased lymphocyte PC-1 activity in type 2 diabetes. However, in contrast to the metformin action, prolonged treatment with two commonly used sulfonylurea agents, gliclazide and glibenclamide, did not produce any significant effect on lymphocyte PC-1. This study has established that sulfonylurea drugs have no effect on PC-1.
Key words:  Diabetes mellitus, insulin resistance, PC-1, sufonylurea treatment, gliclazide, glibenclamide
TERAPIJA PREPARATIMA SULFONILUREJE NEMA EFEKTA NA EKSPRESIJU PC-1 U KULTURI LIMFOCITA PACIJENATA SA TIPOM 2 DIJABETES MELITUSA
Kratak sadržaj: Plazma-ćelijski antigen (PC-1) je inhibitor tirozinkinazne aktivnosti insulinskog receptora i igra značajnu ulogu u nastanku insulinske rezistencije u tipu 2 dijabetes melitusa, gojaznosti i u drugim stanjima koja se karakterišu smanjenjem insulinske senzitivnosti. Saopšteno je da je tromesečni tretman metforminom doveo do smanjenja aktivnosti PC-1 u kulturi limfocita gojaznih tip 2 dijabetičara, sa odgovarajućim poboljšanjem insulinske senzitivnosti. Cilj ovog istraživanja bio je ispitivanje efekta tromesečnog tretmana često korišćenim preparatima sulfonilureje gliklazidom i glibenklamidom na limfocitnu ekspresiju PC-1.
Ispitivanjem je obuhvaćeno 26 novootkrivenih, gojaznih (BMI>30 kg/m2) tip 2 dijabetičara i 14 zdravih osoba (kontrolna grupa). Pre i posle tromesečne terapije gliklazidom (12 pacijenata) i glibenklamidom (14 pacijenata), određene su bazalne, ConA (konkavalin A)-stimulisane i forbol-12-miristat-13-acetat (PMA)-stimulisane vrednosti limfocitnog PC-1.
Nivo glikoze našte kao i nivo fruktozamina statistički su se značajno smanjili nakon tretmana preparatima sulfonilureje. Vrednost PC-1 pre terapije kod gojaznih tip 2 dijabetičara bila je statistički značajno povišena u odnosu na kontrolnu grupu. Tretman gliklazidom ni glibenklamidom nije doveo do statistički značajnog smanjenja aktivnosti limfocitnog PC-1 kako u nestimulisanim, tako i u ConA i PMA stimulisanim limfocitima.
U zaključku, ovo istraživanje potvrđuje prisustvo povišene limfocitne aktivnosti PC-1 u tipu 2 dijabetesa. Za razliku od metformina, dva često korišćena preparata sulfonilureje, gliklazid i glibenklamid, u toku tromesečne terapije nisu dovela do značajnog smanjenja limfocitne aktivnosti PC-1. Ovim istraživanjem utvrđeno je da preparati sulfonilureje nemaju efekta na aktivnost PC-1.
Ključne reči: Dijabetes melitus, insulinska rezistencija, PC-1, preparati sulfonilureje, gliklazid, glibenklamid