Phospholipid Metabolism and Protein Phosphorylation in Sciatic Nerve From Genetically Diabetic (db/db) Mouse

The incorporation of [³²P]orthophosphate into phospholipids and proteins of sciatic nerve from genetically diabetic (db/db) and littermate control (db/m) C57BL/KsJ mice was studied. Nerves from animals of ages 12,16, 22, 26, and 38 wk were incubated in vitro. Among phospholipids, the uptake of isotope into phosphatidic acid was higher at nearly all ages examined. Phosphorylation of several proteins, including the major myelin glycoprotein, P₀, and the small myelin basic proteins P, + P₂, was significantly enhanced in nerves from both 12- and 38-wk-old diabetic mice. The altered pattern of protein phosphorylation, but not that of phospholipid metabolism, was similar to changes observed in sciatic nerve from streptozocin-induced diabetic rats. The relationship of the results to reported levels of myo-inositol, sorbitol, and Na⁺-K⁺-ATPase activity and to functional abnormalities in nerves of db/db mice is discussed. The findings suggest that caution should be exercised in reaching conclusions concerning which biochemical alterations observed in different animal models of diabetic neuropathy are invariably associated with the development of this disorder.