Effect of Long-Term Type 1 Diabetes on Renal Sodium and Water Transporters in Rats

Abstract

The effects of long-term diabetes in the presence of established nephropathy on tubular function remains poorly understood. We evaluated the levels of the main sodium and water transport proteins expressed in the kidney after long-term (8 weeks) of streptozotocin (STZ)-induced type 1 diabetes mellitus (DM) in untreated (D) and insulin (4 U/s.c./day)-treated (D+I) rats. D animals presented upregulation (∼4.5-fold) of Na/glucose cotransporter (SGLT1), whereas the α-subunit of the epithelial sodium channel (α-ENaC) and aquaporin 1 (AQP1) were downregulated (∼20 and 30% respectively) with no change in the Na/H exchanger (NHE3), Na/Cl cotransporter (TSC) and AQP2. Insulin replacement partially prevented these alterations and caused increases in the expression of α-ENaC and AQP2. These effects suggest an action of insulin in the tubular transport properties. The upregulation of SGLT1 may constitute a mechanism to prevent greater glucose losses in the urine but it may result in glucotoxicity to the proximal epithelial cells contributing to the diabetic nephropathy. The decrease of α-ENaC in D animals may compensate for the increased sodium reabsorption via SGLT1 resulting in discrete natriuresis. DM-induced polyuria was not due to changes in AQP2 expression.

The proximal tubule in the pathophysiology of the diabetic kidney

“…The renal cortex of streptozotocin (STZ)-diabetic rats was found to contain increased mRNA expression for SGLT1 and SGLT2 (164) and greater renal SGLT1 protein expression (165). Likewise, renal SGLT1 and SGLT2 mRNA levels in diabetic obese Zucker rats were higher than in age-matched lean rats (136).…”

Probiotics Applications in Autoimmune Diseases

“…In this study, ZT8 was considered as an autoantigen resulting in the stimulation and production of beta cells autoantibodies and T1D development [64]. Moreover, streptozotocin (STZ) had different but significant effect on the expression of Na/Cl/glucose cotransporters, and the administration of insulin reduced such an effect [65]. Hyperglyemia itself directly reduced the activity of Mdr1 suggesting a clear association between pre-T1D hyperglycemia and disturbances in protein transporters [66].…”

Potentials and Limitations of Bile Acids and Probiotics in Diabetes Mellitus

“…In this study, ZT8 was considered as an autoantigen resulting in the stimulation and production of beta cells autoantibodies and T1D development (Rungby 2010). Moreover, streptozotocin (STZ) had different but significant effect on the expression of Na/Cl/glucose cotransporters, and the administration of insulin reduced such an effect (Vidotti et al 2008). Hyperglyemia itself directly reduced the activity of Mdr1 suggesting a clear association between pre-T1D hyperglycemia and disturbances in protein transporters (Tramonti et al 2006).…”