Insulin-Like Partial Effects of Agmatine Derivatives in Adipocytes

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Abstract
Insulin-like effects of agmatine [(4-aminobutyl)guanidine] have been described in vitro. Whether these effects of agmatine can be enhanced by variation in chain length (C3 and C5 forms) and by alkylation was examined. 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 led to a 2-fold, N4-hexyl-C4-agmatine to a 3-fold enhancement of glucose oxidation in adipocytes. Alkylated C4- and C5-agmatines induced a 3-fold increase in lipogenesis compared to agmatine. Alkylation of C3-agmatine did not increase its potency in this test. Insulin decreased adrenaline[epinephrine]-induced lipolysis to 40% of the control value (100%). Agmatine and alkylated C4-agmatines yielded very similar values (37 and 27-44%, respectively). The alkylated C3-agmatines also exerted strongly antilipolytic effects (25-35%), while the effects of the alkylated C5-agmatines were weaker. The synthesized agmatine derivatives were injected i.p. into mice. Tolerable doses did not cause any significant reduction in blood glucose levels.