Expression of myo-inositol cotransporters in the sciatic nerve and dorsal root ganglia in experimental diabetes.

V.X Farias,P.N Uchoa,C.F Santos,C.P Aquino,K.S Silva-Alves,D.B Heimark,M.C Fonteles,L.R.G Britto,N.R.F Nascimento,M.M.G Prata,A Havt,J.H Leal-Cardoso

doi:10.1590/1414-431x20198589

Abstract

The transport of myo-inositol is the main mechanism for the maintenance of its high intracellular levels. We aimed to measure the mRNA and protein levels of myo-inositol cotransporters in the sciatic nerve (SN) and dorsal root ganglia (DRG) during experimental diabetes. Streptozotocin-induced (STZ; 4, 8, and 12 weeks; 65 mg/kg; ip) diabetic rats (DB) and age-matched euglycemic (E) rats were used for the analysis of mRNA and protein levels of sodium myo-inositol cotransporters 1, 2 (SMIT1, SMIT2) or H+/myo-inositol cotransporter (HMIT). There was a significant reduction in the mRNA levels for SMIT1 in the SN and DRG (by 36.9 and 31.0%) in the 4-week DB (DB4) group compared to the E group. SMIT2 was not expressed in SN. The mRNA level for SMIT2 was up-regulated only in the DRG in the DB4 group. On the other hand, the protein level of SMIT1 decreased by 42.5, 41.3, and 44.8% in the SN after 4, 8, and 12 weeks of diabetes, respectively. In addition, there was a decrease of 64.3 and 58.0% of HMIT in membrane and cytosolic fractions, respectively, in the SN of the DB4 group. In the DRG, there was an increase of 230 and 86.3% for SMIT1 and HMIT, respectively, in the DB12 group. The levels of the main inositol transporters, SMIT1 and HMIT, were greatly reduced in the SN but not in the DRG. SMIT-1 was selectively reduced in the sciatic nerve during experimental STZ-induced diabetes.

Highlights

Myo-inositol is a natural cyclitol that is mostly obtained from diet but is synthesized in the kidney
In order to check for sciatic nerve (SN) function, we evaluated chronaxy, rheobase, conduction velocity, and nerve growth factor (NGF) expression levels
The rheobase of the DB8 and DB12 groups had a significant increase of 7.9% and 14.4%, respectively, compared to rheobase that was observed in the respective E groups (3.4±0.09 V and 3.45±0.09 V vs 3.01±0.09 V and 3.15±0.06 V, respectively)

Summary

Introduction

Myo-inositol is a natural cyclitol that is mostly obtained from diet but is synthesized in the kidney. This compound is an organic osmolyte protecting cells from osmotic stress and a precursor of inositolphosphoglycans, phosphatidylinositols, and phosphoinositides that are involved in signal transduction [1]. The synthesis of PI requires a relatively high Km (1.5–2.5 mM) making intracellular myo-inositol homeostasis very important to numerous cell activities [2,3]. Myo-inositol and D-chiro-inositol are components of glycosyl-phosphatidylinositol anchors and inositol phosphoglycans, which are second messengers of insulin action [2,3]. Myo-inositol has been shown to improve glucose tolerance in both animals and humans [1,4,5]

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