Elsevier

Life Sciences

Volume 64, Issue 16, 12 March 1999, Pages 1427-1434
Life Sciences

The effect of an insulin releasing agent, BTS 67 582, on advanced glycation end product formation in vitro

https://doi.org/10.1016/S0024-3205(99)00076-4Get rights and content

Abstract

BTS 67 582 (1,1-dimethyl-2-(2-morpholinophenyl) guanidine fumarate) is an insulin-releasing agent currently in phase II clinical trials. Its effect on advanced glycation end product (AGE) formation was measured in the BSA/D-glucose and L-lysine/glucose-6-phosphate assay systems and Amadori product formation was measured in the BSA/D-glucose assay system, following a 3 week incubation period. In the BSA/D-glucose assay system, 200 mM BTS 67 582 caused an approximate 70 % inhibition in AGE formation (p < 0.001), whilst at 20 mM and 2 mM it caused a marginal inhibition (21 %, (p < 0.001) and 8 % respectively). 200 mM and 20 mM aminoguanidine-HCl inhibited AGE formation by 95 % and 69 % (p < 0.001), respectively, whereas 2 mM aminoguanidine-HCl had no significant effect. Tolbutamide (200 μM) and glibenclamide (100 μM) had significant, but only marginal, effects on AGE formation (16 % and 17 %, respectively, p < 0.01). In the BSA/D-glucose assay system 200 mM BTS 67 582 and 200 mM aminoguanidine-HCl retarded Amadori product formation by 88 % (p < 0.001) and 60 % (p < 0.01), respectively. BTS 67 582 at 20 mM and 2 mM was shown to inhibit Amadori product formation by 67 % and 57 %, respectively, (p < 0.01). In the lysine and glucose-6-phosphate assay system 200 mM BTS 67 582 and 200 mM aminoguanidine-HCl were shown to inhibit AGE formation by about 70% and 96% (p < 0.001), respectively. Tolbutamide (200 μM) and glibenclamide (100 μM) had no significant effect on AGE formation.

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  • Cited by (1)

    Annemarie Simpson, Knoll Pharmaceuticals, Biology, Research and Development, Pennyfoot Street, NOTTINGHAM, NG1 1GF. Tel: 0115 912 4215; FAX: 0115 912 4169.

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