Renal Na-K-ATPase hyperactivity in diabetic Psammomys obesus is related to glomerular hyperfiltration but is insulin-independent

Abstract

Psammomys obesus, a desert rodent, develops diabetes when displaced from its natural environment and fed a high energy diet in the laboratory. This study was designed to examine variations in renal function in relation to the diabetic state with emphasis on changes in Na-K-ATPase activity.The following groups of Psammomys were studied: (1) Animals fed a saltbush diet; a low energy/high salt diet (natural). (2) Animals fed a low energy/low salt diet (laboratory). Both 1 and 2 were normoglycemic and normoinsulinemic and thus served as control. (3) Animals fed a high energy diet (group C) who were hyperglycemic and hyperinsulinemic; this group was divided into two subgroups: C1 presented with glomerular hyperfiltration rate and C2 with glomerular hypofiltration rate. (4) Animals fed a high energy diet presenting with hyperglycemia-hypoinsulinemia (group D). (5) Group D+I, similar to group D but treated with external insulin (2 U/24 h).Groups D and C1, whose glomerular filtration rose above normal by 30% and 70% respectively, exhibited metabolic similarity to Type I and Type II diabetes. In these groups, Na-K-ATPase activity in the cortex increased by 80-100% and in the medulla by 180% (P<0·001 vs control). In group C2 with reduced glomerular filtration rate (GFR), Na-K-ATPase activity did not differ from control. In group D+I, with normalized glomerular filtration rate, Na-K-ATPase activity was similar to control. There was a linear and significant correlation between GFR and Na-K-ATPase activity both in the cortex and in the medulla.These experiments present a well defined animal model of diabetes mellitus. Variations in glucose and in insulin did not correlate with Na-K-ATPase activity. These results clearly demonstrated that Na-K-ATPase activity in the diabetic Psammomys was determined by glomerular filtration but was independent of plasma glucose or insulin levels.

Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats

“…Decreased Na + K + ATPase activity resulted in increased diuresis as the removal of sodium from the various sites in nephron (reabsorption) is affected. According to Scherzer et al [40], a rodent Psammomys obesus develops diabetes when displaced from its natural environment and fed a high energy diet in the laboratory. The increase in Na-K-ATPase activity in diabetic rat with increased urine flow was similar to that which was previously observed in diabetic P. obesus [40].…”

“…According to Scherzer et al [40], a rodent Psammomys obesus develops diabetes when displaced from its natural environment and fed a high energy diet in the laboratory. The increase in Na-K-ATPase activity in diabetic rat with increased urine flow was similar to that which was previously observed in diabetic P. obesus [40]. This correlates with a significant decrease in Na + K + ATPase and corresponding decrease in the urine volume in TG (100 mg/kg) group.…”

Acute Kidney Injury in the Diabetic Rat: Studies in the Isolated Perfused and Intact Kidney

“…The propensity of the isolated perfused diabetic kidney to a more pronounced functional derangement and cell damage may reflect enhanced tubular transport for salt reabsorption [4] or perhaps intense reduction in perfusate flow (suggesting vascular/endothelial dysfunction) under the most extreme experimental hypoxic conditions. Renal denervation in the ex vivo isolated perfusion model may also have a more profound effect upon the outcome of acute hypoxia in the diabetic kidney.…”

“…Renal hypoxia develops within 1 week after the induction of experimental diabetes with streptozotocin (STZ), leads to the generation of hypoxia-inducible factors (HIF), and is prevented by insulin treatment [3]. Renal hypoxia in the diabetic kidney may represent enhanced oxygen consumption for tubular transport [1, 4] and altered renal microcirculation [5, 6]. …”

Proinsulin C-peptide reduces diabetes-induced glomerular hyperfiltration via efferent arteriole dilation and inhibition of tubular sodium reabsorption

“…Approximately 80% of total kidney QO 2 is related to tubular electrolyte transport (4). Numerous studies have reported increased renal Na ϩ -K ϩ -ATPase activity and increased QO 2 during the early hyperfiltration phase in streptozotocin (STZ)-induced diabetes (5,27,28,58) and in other models of experimental diabetes (50). It has even been suggested that alterations in renal proximal Na ϩ -K ϩ -ATPase activity may regulate GFR (30).…”