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. 1990 Dec;87(24):9818–9822. doi: 10.1073/pnas.87.24.9818

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

X Zhu 1, J Eichberg 1
PMCID: PMC55265  PMID: 2263632

Abstract

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

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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