Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

Abstract

The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor) was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin) and protein excretion rate (PER) were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P < .001), Cinulin increased 80% (P < .01). Kidney wet and dry weights increased 10%–12% (P < .05), and glomerular tuft area increased 9.3% (P < .001). Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes

“…Previous experimental work using different animal models of kidney disease have demonstrated that SGLT2 inhibition alleviates renal damage. In Akita and streptozotocin-induced animal models of insulin-deficient diabetes, SGLT2 inhibition reduced albuminuria [18][19][20]. SGLT2 inhibition has similar anti-albuminuric effects in animal models of type 2 diabetes [21], including recent evidence that empagliflozin reduced albuminuria, independent of effects on BP or hyperglycaemia, in BTBR ob/ob mouse models of type 2 diabetes [22].…”

Ameliorated pancreatic &beta; cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

“…A previous study suggested that phlorizin, a SGLT inhibitor and not a selective SGLT2 inhibitor, had an inhibitory effect on the tubular reabsorption of β2-microglobulin in control and diabetic rats [33]. It might be that ipragliflozin similarly affected the tubular reabsorption of β2-microglobulin.…”

Use of unripe plantain (Musa paradisiaca) in the management of diabetes and hepatic dysfunction in streptozotocin induced diabetes in rats

“…The renal hypertrophy of the diabetic control rats suggests their progression to the development of renal pathology [16] while the decrease in the relative kidney weights of the diabetic rats fed unripe plantain suggests the ability of unripe plantain to ameliorate renal hypertrophy.…”