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Applicability of red blood cell sorbitol measurements to monitor the clinical activity of sorbinil.

Metabolism: clinical and experimental (1986-04-01)
M J Peterson, M G Page, L J Just, C E Aldinger, J I Malone
ABSTRACT

Increased flux of glucose through the polyol pathway with resultant resultant accumulation of tissue sorbitol is implicated in the pathogenesis of the chronic complications of diabetes. Sorbinil is a potent inhibitor of aldose reductase (the first enzyme in the polyol pathway) and has been shown to normalize sorbitol levels in relevant tissues (eg, nerve, kidney, lens) of experimentally-induced diabetic animals. The purpose of this study was to identify a relatively noninvasive method of monitoring the intrinsic (or biochemical) efficacy of sorbinil in diabetic man. Specifically, the objective was to identify a readily accessible tissue that would be reflective of polyol pathway activity and the activity of sorbinil in clinically relevant but less accessible tissues. Based on several previous studies, which demonstrated that sorbitol accumulation in human red blood cells (RBCs) was a function of ambient glucose concentrations, either in vitro or in vivo, our investigations were conducted to determine if RBC sorbitol accumulation would correlate with sorbitol accumulation in lens and nerve tissue of diabetic rats; the effect of sorbinil in reducing sorbitol levels in lens and nerve tissue of diabetic rats would be reflected by changes in RBC sorbitol; and sorbinil would reduce RBC sorbitol in diabetic man.

MATERIALS
Product Number
Brand
Product Description

Sorbitol, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
D-Sorbitol, BioReagent, suitable for cell culture, suitable for plant cell culture
Sigma-Aldrich
D-Sorbitol, ≥98%
Sigma-Aldrich
D-Sorbitol, BioXtra, ≥98%
Sigma-Aldrich
D-Sorbitol, for molecular biology, ≥98%
Sigma-Aldrich
D-Sorbitol, BioUltra, ≥99.0% (HPLC)
Supelco
Sorbitol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
D-Sorbitol, FCC, FG
Sigma-Aldrich
D-Sorbitol, 99%
Sigma-Aldrich
D-Sorbitol, liquid, tested according to Ph. Eur.
Sigma-Aldrich
Sorbitol F solution, 70 wt. % in H2O, Contains mainly D-sorbitol with lesser amounts of other hydrogenated oligosaccharides