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Renal globotetraosylceramide expression in rat model of diabetes type 1

Globotetraosylceramide (Gb4Cer, GalNAc alpha1-3Gal alpha1-4Gal alpha1-4 Glc alpha1-1Cer) has been identified among the major renal neutral glycosphingolipids. Gb4Cer molecules are found in membrane lipid rafts where they can influence the function of receptors and transporters embedded in these domains. Apical membranes of the kidney proximal tubule epithelial cells contain lipid rafts that support absorptive strategy for nutrient reabsorption. Considering diabetic nephropathy and changed glycosphingolipid metabolism in diabetes, the aim of our study was to determine renal Gb4Cer expression in rat model of diabetes type 1. Diabetes was induced with streptozotocin (55 mg kg−1) injection two weeks before Gb4Cer analysis in the kidney of Sprague-Dawley rats weighing 140-160 g (8 males and 5 females) and compared to respective control animals (3 males and 3 females). Gb4Cer fractions in the tissues of diabetic and control rats were determined by high performance thin-layer chromatography (HPTLC), followed by immunostaining with specific anti-Gb4Cer polyclonal antibody. Diabetic male rats showed increased expression of Gb4Cer. In addition, two bands of Gb4Cer derivative (corresponding to sulphated Gb4Cer), chromatographed bellow Gb4Cer, were also increased in diabetic male rats compared to control. In contrast to control male rats, control female rats had lower Gb4Cer and only one Gb4Cer derivative band. Diabetic female rats showed lower expression of Gb4Cer and Gb4Cer derivative compared to control female rats. Results of this study are significant in the view of the risk to develop end-stage renal disease that is doubled in men compared with women when age at diabetes type 1 onset is ≥15 years. Knowing that estrogen treatment decreases the content of Gb4Cer in rat kidney, our results point at the role of Gb4Cer in nephropathy development particularly in males.

globotetraosylceramide rat diabetes type 1

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