Myocardial inositol and sodium in diabetes.
Although inhibition of Na(+)-K+ ATPase has been described in the diabetic heart, K+ loss from myocardium has not been observed in a canine model of mild diabetes. The finding of tissue Na+ accumulation and a potential relation to alteration of left ventricular inositol as observed in other tissues in diabetes form the basis of this investigation. Diabetes was induced with alloxan in three groups of male mongrel dogs who were studied after 1 yr. In the initial experiment the tissue compartment volumes, determined with intravenous 51Cr EDTA as a marker, were found to be normal. Calculated cell sodium was increased to 32.8 +/- 2.6 mEq/kg cell H2O vs 18.7 +/- 1.1 in controls (p < 0.01). Cell potassium in diabetes was normal. In the second group, myocardial polyols were analyzed by gas-liquid chromatography. Inositol was diminished in diabetes to 0.61 +/- 23 microM/g of left ventricle, vs the respective control levels of 1.9 +/- 0.57 microM/g (p < 0.02). Sorbitol concentration was unaltered. Left ventricular sodium increments were not associated with altered tissue calcium. In group III the hypothesis that inhibition of Na(+)-K+ ATPase in diabetes might not elicit the expected alteration of K+ transport was assessed during intracoronary infusion of acetyl strophanthidin. No difference in cation responses from control was observed. It is postulated that a change in the conformation of Na(+)-K+ ATPase, with high affinity sodium binding sites facing the intracellular compartment, may render sodium less releasable from cell membrane.
Regan
T J
TJ
Department of Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
Beyer-Mears
A
A
Torres
R
R
Fusilli
L D
LD
D000818:Animals; D001706:Biopsy; D001825:Body Fluid Compartments; D002849:Chromatography, Gas; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005069:Evaluation Studies as Topic; D006439:Hemodynamics; D007294:Inositol / Q000737:chemistry*; D007424:Intracellular Fluid / Q000737:chemistry*; D008297:Male; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism; D011188:Potassium / Q000737:chemistry; D012964:Sodium / Q000737:chemistry*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism* / Q000502:physiology; D013012:Sorbitol / Q000737:chemistry; D014018:Tissue Distribution
D007294:Inositol; D013012:Sorbitol; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium