Effect of myo-inositol on cell proliferation and collagen transcription and secretion in proximal tubule cells cultured in elevated glucose.
Tubulointerstitial lesions often develop in the kidneys of patients and experimental animals with diabetes mellitus. In an in vitro model of diabetic renal disease, it has been previously demonstrated in this laboratory that elevated glucose levels stimulate procollagen transcription and secretion in proximal tubule cells in culture while inducing cellular hypertrophy and reducing cellular proliferation. Previous experiments in other tissues have suggested that myo-inositol supplementation, probably by reversing a disturbance in cell myo-inositol metabolism related to increased activity of the polyol pathway, reverses the effects of glucose on cell function. We tested the effect of myo-inositol supplementation on proximal tubule cells in culture in the presence of elevated medium glucose level. Incubation in 450 mg/dL of glucose media reduced cell proliferation; 450 mg/dL of glucose plus myo-inositol (800 microM) increased proliferation, returning the value to that seen in cells incubated in 100 mg/dL of glucose. Incubation in 450 mg/dL of glucose media increased type IV and type I procollagen mRNA levels and peptide secretion rates compared with those seen in cells incubated in medium containing 100 mg/dL of glucose. This glucose-induced stimulation of procollagen mRNA levels and procollagen secretion was not observed when the elevated glucose medium was supplemented with 800 microM myo-inositol. On the other hand, myo-inositol supplementation did not prevent the glucose-induced cellular hypertrophy: there was no reduction in the increased leucine incorporation and cellular protein content. Cell incubation in 450 mg/dL of glucose media did not lead to a measurable decrease in total cellular myo-inositol.(ABSTRACT TRUNCATED AT 250 WORDS)
Ziyadeh
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Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6144.
Simmons
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Snipes
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Goldfarb
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000209:etiology; D005947:Glucose / Q000494:pharmacology*; D007294:Inositol / Q000378:metabolism / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011347:Procollagen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D011347:Procollagen; D012333:RNA, Messenger; D007294:Inositol; D005947:Glucose