HIGH PROTEIN DIETS STIMULATE RENAL PROTEIN OXIDATION IN EXPERIMENTAL DIABETES.

Abstract

Calorie restriction increases macro- and chaperone-mediated autophagy (MA & CMA) protecting against organ damage by destroying oxidized proteins (OX) and p62/sequestisome 1 labeled aggregates (p62). Altering dietary protein changes kidney damage in DM, but the effect on renal cortical MA, CMA, OX and p62 is unknown. 60 mg/kg streptozotocin Diabetic (D) Sprague-Dawley rats (200 g) or control (C) were fed isocaloric 12% (L), 23% (M) or 40% (H) protein diets for 21 days (6 groups, each n= 7-11). Body weight at 21 days was 16-22% lower than C in all D rats (p<0.01, NS between diets). Blood glucose was lower in DH vs. DL diets (408+25vs. 482+23 mg/dl, p<0.05). Kidney wt/body wt increased in all DM groups, but increase was greater in DH than DL (104+13 vs. 66+11%, p<0.02). MA, CMA, and p62 were estimated by western blotting for light chain 3b II/I ratio, lysosome associated membrane protein 2a, and p62 respectively, while OX was measured by Oxyblot. D reduced CMA by 65-76% (p<0.05 vs. C) while H diet reduced it by ∼45% in C and D rats (NS). MA increased in all D, but was ∼10 fold higher in HD vs. HC or LD (p<0.02). There was a trend toward increased OX with D, but only HD reached significance vs. all C (95+32%, p<0.05). The trend for p62 to increase with D or H was NS. We conclude that despite lower glucose, H diets worsen diabetic renal hypertrophy and cortical OX possibly by suppressing CMA. Increases in MA by D and H prevent p62 protein aggregates from accumulating.