Protein kinase C agonists acutely normalize decreased ouabain-inhibitable respiration in diabetic rabbit nerve. Implications for (Na,K)-ATPase regulation and diabetic complications.
Diminished (Na,K)-ATPase activity in diabetic peripheral nerve is attributed to an underlying depletion of free myo-inositol, but no biochemical mechanism linking myo-inositol metabolism and (Na,K)-ATPase has emerged. Since inositol phospholipid turnover releases inositol-(1,4,5)-tris-phosphate and diacylglycerol, two putative "second messengers" that modulate protein kinase C, the effect of protein kinase C agonists on (Na,K)-ATPase activity was examined in diabetic nerve. Phorbol myristate acetate or the diacylglycerol sn-1,2-dioctanoylglycerol acutely normalized depressed ouabain-inhibitable respiration [a measure of (Na,K)-ATPase activity], suggesting that myo-inositol metabolism modulates (Na,K)-ATPase activity via protein kinase C, and that reduced myo-inositol impairs (Na,K)-ATPase activity in diabetic nerve by this mechanism.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000201:enzymology / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D007294:Inositol / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D005989:Glycerides; D010704:Phorbols; C044295:1,2-dioctanoylglycerol; D007294:Inositol; D010042:Ouabain; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D013755:Tetradecanoylphorbol Acetate