ENDOGENOUS DIGOXIN-LIKE IMMUNOACTIVITY AND DIABETES-MELLITUS - FACTS AND HYPOTHESES

Substances with digoxin-and ouabain-like immunoactivity (DLIA) are spe cific inhibitors of Na+-K+-ATPase which increase the total amount of i ntracellular stored calcium (Ca-i(2+)). In diabetic patients, DLIA lev els have been reported to be increased. Although this increase is prob ably secondary to sodium retention and volume expansion (induced in di abetic subjects by hyperinsulinemia and/or diabetic nephropathy), the question arises of whether it has pathophysiological consequences: nam ely, whether substances with DLIA, via their effect on Na+-K+-ATPase a ctivity and Ca-i(2+), stores, could in diabetic subjects facilitate de velopment of hypertension and/or modulate insulin sensitivity or insul in secretion. Clinical findings of correlations of DLIA to blood press ure, insulin levels and to degree of insulin resistance, together with experimental findings of decreased Na+-K+-ATPase activity, increased Ca2(i)(+) and decreased Mg-i(2+) in both diabetic and hypertensive sub jects, support these hypotheses. However, the issue of whether or not these relations are causative and whether or not defects in intracellu lar milieu are primary or secondary to non-insulin-dependent diabetes mellitus has not been resolved yet. Moreover, pathogenesis of both dia betes mellitus and hypertension is multifactorial and includes many ot her factors. Therefore, further efforts should be made to elucidate th e exact role of substances with DLIA in diabetes mellitus.