Vol. 9, No 3, 2002 pp. 207 - 212
UC 616.379-008.64:616-085
IMMUNOMODULATORY ENZYMES AND DIABETES
Maja Milojković1, Predrag Vlahović2,
Slobodan Antić3, Vladisav Stefanović2
1Institute of Pathophysiology, 2Institute
of Nephrology and Hemodialysis
3Clinic of Endocrinology, Diabetes
and Metabolic Disorders, Medical Faculty, Niš, Serbia
Summary. Immunomodulatory ectoenzymes are proteins localized on
cell membranes, with active sites exposed to the extracellular surface,
involved into cell-to-cell communication, cellular growth and differentiation
processes. Alterations of their activity are found in both type 1 and type
2 diabetes, thus attracting a growing interest in their investigation.
PC-1 (an enzyme with alkaline phosphodiesterase/nucleotide pyrophosphatase
activity) inhibits the insulin receptor tyrosine kinase activity by direct
binding to the insulin receptor a subunit, thereby representing a key suspect
for impaired insulin signaling in obese insulin resistant type 2 diabetics.
Overexpression of PC-1 was found in various tissues of type 2 diabetics,
as well as in obese insulin resistant rhesus monkeys, confirming its role
in pathogenesis of insulin resistance. Oral treatment with metformin was
found to decrease a level of PC-1 in cultured lymphocytes of type 2 diabetics,
thus suggesting a possible mechanism of metformin action in target tissues.
Other immunomodulatory enzymes reviewed in this article (5'-Nu, DPP IV,
APN) also play an important role in understanding of diabetes and progression
of its complications. A certain progress has been made in the therapeutic
aspect with DPP IV inhibitors, while APN and 5'-Nu could be useful in recognition
of diabetic complications. Therefore further investigations of the relation
between immunomodulatory enzymes and pathogenesis of diabetes would be
of great benefit for both diabetics and clinicians dealing with diabetes.
Key words: Immunomodulatory enzymes, PC-1, DPP IV, 5'-nucleotidase,
diabetes, insulin resistance
IMUNOMODULATORNI ENZIMI I DIJABETES
Kratak sadržaj: Imunomodulatorni enzimi su proteini ćelijske membrane
sa ekstracelularnim aktivnim domenima, koji učestvuju u međusobnoj interakciji
ćelija, procesu ćelijskog rasta i diferencijacije. Izmenjena aktivnost
nekih imunomodulatornih enzima dovodi se u vezu sa patogenezom dijabetesa
i njegovih hroničnih komplikacija. Naročiti značaj savremena iztraživanja
pridaju PC-1 molekulu, enzimu koji poseduje aktivnost alkalne fosfodiesteraze
I i nukleotid pirofosfataze, i koji inhibiše tirozin kinaznu aktivnost
insulinskog receptora direktnim vezivanjem za njegovu alfa podjedinicu.
Za razliku od insulinosenzitivnih dijabetičara i zdravih osoba, prekomerna
ekspresija PC-1 nađena je u ciljnim tkivima gojaznih, insulinorezistentnih
tip 2 dijabetičara, kao i kod gojaznih insulinorezistentnih rezus majmuna,
što ukazuje na ulogu PC-1 u patogenezi insulinske rezistencije. Oralna
terapija metfominom smanjuje limfocitnu aktivnost PC-1 kod tip 2 dijabetičara,
što ukazuje na mogući mehanizam delovanja metformina na nivou ciljnih tkiva.
Drugi imunomodulatorni enzimi koji mogu imati značaja u patogenezi dijabetesa
su DPP IV, 5'-nukleotidaza i APN. Postoje istraživanja vezana za terapijsku
upotrebu DPP IV inhibitora, dok APN i 5'-Nu mogu koristiti u otkrivanju
komplikacija dijabetesa. Literaturni podaci pokazuju da dalja istraživanja
uloge imunomodulatornih enzima u nastanku dijabetesa i njegovih komplikacija
mogu biti od velikog fundamentalnog i praktičnog značaja.
Ključne reči: Imunomodulatorni enzimi, PC-1, DPP IV, 5'-nukleotidaza,
dijabetes, insulinska rezistencija
