Mannose, glucosamine and inositol monophosphate inhibit the effects of insulin on lipogenesis. Further evidence for a role for inositol phosphate-oligosaccharides in insulin action.

摘要: The mechanism of insulin signalling is not yet understood in detail. Recently, a role for inositol phosphate (IP)-oligosaccharides as second messengers transmitting the signal at post-kinase level was proposed. To evaluate this hypothesis further, we studied whether IP-oligosaccharides isolated from 'haemodialysate' have insulin-like activity. We found that these compounds mimic, dose-dependent fashion, following effects adipocytes. (1) Lipogenesis. Incorporation [3H]glucose into lipids (expressed nmol/min per 10(6) cells): basal, 0.74 +/- 0.05; (1 mu unit/ml), 4.43 0.21; IP-oligosaccharide (2 micrograms/ml), 4.07 0.19. (2) Inhibition isoprenaline (isoproterenol) microM)-stimulated cyclic AMP levels and lipolysis. Cyclic (pmol/10(5) basal 0.84 isoprenaline, 4.03 0.19; + (200 units/ml), 2.06 0.7; 2.4 0.29. lipolysis (mumol glycerol/mg protein): microM), 166 11; isoprenaline+insulin (150 53 3.5; isoprenaline+IP-oligosaccharides 58 5. (3) Stimulation 3-O-methylglucose transport; 9 3%; 67 4%, 54 2%. identify active molecules fraction, competition experiments were performed. on lipogenesis blocked by monophosphate, glucosamine mannose. In contrast, did inhibit membrane-mediated functions (3-O-methylglucose transport, levels, lipolysis). also effect mannose, whereas 3-O-methylglucose, unaffected. conclusions reached. mimic major metabolic This consistent with proposed certain effects. Mannose are functionally important sugar residues lipogenesis. observation monophosphate block action supports mannose- glucosamine-containing effect.