Insulin-like partial effects of agmatine derivatives in adipocytes.
In previous investigations, we described insulin-like effects of agmatine [(4-aminobutyl)guanidine] in vitro. In the present work we have examined whether these effects of agmatine can be enhanced by variation in chain length (C3 and C5 forms) and by alkylation. Propyl, butyl, pentyl, hexyl, octyl, isobutyl and isopentyl groups were introduced into C4- and C5-agmatine by hydrogenation of the corresponding azomethines. Alkylation of C3-agmatine was carried out by addition of alkylamines to acrylonitrile, followed by hydrogenation and amidination. For the biological assays, isolated fat cells from rat epididymic adipose tissue were used. N4-Butyl- and N4-pentyl-C4-agmatines lead to a two-fold, N4-hexyl-C4-agmatine to a three-fold enhancement of glucose oxidation in adipocytes. Alkylated C4- and C5-agmatines induce a three-fold increase in lipogenesis compared to agmatine. Alkylation of C3-agmatine does not increase its potency in this test. In our test system, insulin decreases adrenalin-induced lipolysis to 40% of the control value (100%). Agmatine and alkylated C4-agmatines yield very similar values (37% and 27-44% respectively). The alkylated C3-agmatines also exert strongly antilipolytic effects (25-35%), while the effects of the alkylated C5-agmatines are weaker. The synthesized agmatine derivatives were injected intraperitoneally into mice. Tolerable doses do not cause any significant reduction in blood glucose levels.
D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000376:Agmatine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D000478:Alkylation; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
D006146:Guanidines; D007328:Insulin; D008055:Lipids; D000376:Agmatine; D005947:Glucose