Glucose and scyllo-inositol impair phosphoinositide hydrolysis in the 10.5-day cultured rat conceptus: A role in dysmorphogenesis?

摘要: Culture of the postimplantation rat conceptus from gestational day 9.5-10.5 in media supplemented with d-glucose or scyllo-inositol decreases tissue myo-inositol and phosphoinositides a concomitant increase dysmorphogenesis. A number mitogenic agents initiate cellular proliferation differentiation through receptors coupled to phosphoinositide hydrolysis. To test whether decrease is associated reduced hydrolytic response, we developed protocol stimulate Phosphoinositide hydrolysis was monitored by measurement [3H]inositol phosphates after preincubation serum free media. We examined ability serum, platelet-derived growth factor (PDGF), epidermal-derived (EGF), insulin-like 1 (IGF-1), 2 (IGF-2), endothelin-1 (ET-1), endothelin-2 (ET-2), As measured monophosphate ([3H]InsP1) accumulation, normal seru, ET-1, ET-2 stimulated 47%, 420%, 154% above basal rate observed controls. EGF statistically insignificant 15% while PDGF, IGF-1, IGF-2 were without effect. further characterized ET-1 Dose-response studies disclosed that incremental increases [3H]InsP1 (129-420%) are over concentration range 10-1,000 nM. Maximal stimulation not reached even at 1,000 Temporally [3H]InsP3 levels increased linearly during incubation periods 15-60 min. analyzed 10.5-day conceptuses cultured for 24 hr containing high concentrations glucose (23.3-56.6 mM) (0.55, 5.5 mM). Under these dysmorphogenic conditions concomitantly precursor pool response blunted 28-76% 29-65% scyllo-inositol. This suggests effect on lowering pools also results agonists using inositol/lipid intracellular pathway. impaired signaling may contribute initiating events diabetic embryopathy.