Insulin bound to chiral polymer with N-acetyl-D-glucosaminyl units. Lacks of mitogenic activity on rat aorta smooth muscle cell proliferation.
Insulin was covalently attached to two terpolymers of N-(2-hydroxypropyl) methacrylamide, N-methacryloyldiglycine and a) R-(-)-1-methyl-2-methacryloylamidoethyl 2-acetamido-2-deoxy-beta-D-glucopyranoside or b) S-(+)-1-methyl-2-methacryloylamidoethyl 2-acetamido-2-deoxy-beta-D-glucopyranoside. The mitogenic effect of both conjugates on vascular smooth muscle cell proliferation was investigated. The results indicated that insulin bound to both carriers with pendant N-acetylglucosaminyl groups possesses hypoglycemic activity but not the mitogenic effect of native insulin. This study shows that for these insulin conjugates, the effect does not depend on the steric configuration of the sugar-containing monomer units incorporated in the terpolymer. A hypothesis is developed that some competition is taking place between N-acetylglucosaminyl groups on the polymeric insulin carrier and the same moieties in the insulin receptor expressed on the surface of smooth muscle cells leading to a lack of mitogenic activity.
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
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Chytry
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Letourneur
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Vrana
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Jozefonvicz
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011108:Polymers / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D007004:Hypoglycemic Agents; D007328:Insulin; D008934:Mitogens; D011108:Polymers