Conjugates of insulin with copolymers of N-(2-hydroxypropyl) methacrylamide: effects on smooth muscle cell proliferation.
The hypothesis that an elevated plasma insulin level contributes to an increase in coronary heart disease has led to studies of the mitogenic effect of native insulin and its conjugates on smooth muscle cells (SMC). In this study, insulin was covalently attached to two water-soluble polymers containing N-(2-hydroxypropyl)methacrylamide using the mixed anhydride method. The first polymer was a copolymer of N-(2-hydroxypropyl)methacrylamide and N-methacryloyldiglycine. The second one was a terpolymer of two of the above-given monomers and R-(-)-1-methyl-2-methacryloylamidoethyl 2-acetamido-2-deoxy-beta-D-glucopyranoside. Insulin conjugates were isolated and characterized, and the mitogenic effect on SMC was investigated. The results showed that only conjugates of insulin and terpolymers bearing pendant N-acetyl-glucosamine groups do not have a mitogenic effect on SMC while maintaining the hypoglycemic activity of insulin. This finding suggests that some inter- or intramolecular interactions of coupled insulin with the sugar moiety(ies) attached to the polymer backbone contribute to the observed effects.
Chytry
V
V
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic Prague, Czech Republic.
Letourneur
D
D
Baudys
M
M
Jozefonvicz
J
J
D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D007328:Insulin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013552:Swine; D013936:Thymidine / Q000378:metabolism; D000099166:Polyacrylamides
D000180:Acrylic Resins; D001786:Blood Glucose; D004247:DNA; D007328:Insulin; D013936:Thymidine; D000099166:Polyacrylamides