A myo-inositol pool utilized for phosphatidylinositol synthesis is depleted in sciatic nerve from rats with streptozotocin-induced diabetes.

• DOI: 10.1073/pnas.87.24.9818
• Publication Date: 2006-05-31T11:32:52Z
• Authors: X Zhu; J Eichberg
• Keywords: Male; 0303 health sciences; Phosphatidic Acids; Rats, Inbred Strains; Cytidine; Phosphatidylinositols; Propranolol; Sciatic Nerve; Diabetes Mellitus, Experimental; Rats; Kinetics; 03 medical and health sciences; Reference Values; Animals; Chromatography, Thin Layer; Inositol; Phospholipids

Peripheral nerve from experimentally diabetic rats exhibits lowered levels of myo-inositol (MI) and decreased incorporation [3H]MI into phosphatidylinositol (PI). There are indications that diminished PI turnover may be causally related to reduced Na+,K(+)-ATPase activity in nerve. We have investigated whether a metabolic compartment MI is essential for synthesis this tissue. Sciatic segments streptozotocin-induced age-matched normal were incubated vitro with either 32Pi or [3H]cytidine the presence propranolol. This cationic amphiphilic agent redirected phospholipid metabolism produce enhanced 32P labeling phosphatidylcholine phosphatidyl-ethanolamine. The accumulation phosphatidyl CMP (CMP-PA) was also demonstrated by chromatographic enzymatic means. CMP-PA increased up 15-fold when 0.6 mM propranolol present. In nerve, liponucleotide incorporated 2- 3-fold more isotope readily labeled at lower drug concentrations as compared buildup [3H]CMP-PA dose-dependent manner incubation medium 3 mM. However, if added after accumulation, preformed could not utilized synthesis. difference between nearly abolished 0.3 MI, concentration much less than level cyclitol These results strongly suggest pool equilibrium bulk preferentially used depleted but can replenished exogenous correspond has been proposed required portion tissue involved maintenance activity.