Insulin-induced lipid binding to hemoglobin

Abstract

Under hypoglycemic conditions, concomitant hyperinsulinism causes an apparent modification of hemoglobin (Hb) which is manifested by its a aggregation (Niketic et al.. Clin. Chim. Acia 197 (1991) 47). In the present work the causes and mechanisms underlying this Hb modification were Studied. Hemoglobin isolated from normal erythrocytes incubated with insulin was analyzed by applying P-31-spectrometry and lipid extraction and analysis. To study the dynamics of the plasma membrane during hperinsulinisra a fluorescent lipid-analog was applied. In the presence of insulin phosphatidylserine (PS). phosphatidylethanolamine (PE) and cholesterol were found to bind to Hb. Lipid binding resulted in Hb aggregation, a condition that can be reproduced when phospholipids arc incubated with Hb in vitro. Using a fluorescent lipid-analog, it was also shown that exposing crythrocytes to supraphysiological concentrations of insulin in vitro resulted in the internalization of lipids. The results presented in this work, may have relevance to cases of diabetes mellitus and hypoglycemia.

Uranijim radovima je pokazano da hiperinsulinizam u uslovima hipoglikemije izaziva modifikaciju molekula hemoglobina koja se manifestuje njegovim agregiranjem (Niketić et al., Clin. Chim. Acta 197 (1991) 47). U ovom radu ispitivana je ova modifikacija molekula hemoglobina, kao i mehanizam njenog nastajanja. Primenom 31P-spektrometrije i analizom lipidnog ekstrakta utvrđeno je da u normalnim eritrocitima inkubiranim sa insulinom dolazi do vezivanja fosfatidil-serina, fosfatidil-etanolmina i holesterola za molekul hemoglobina. Vezivanje fosfolipida za hemoglobin dovodi do njegovog agregiranja što je potvrđeno eksperimentima u kojima je hemoglobin inkubiran sa fosfolipidima in vitro. Primenom fluorescentnog lipidnog analoga pokazano je da pri izlaganju eritrocita suprafiziološkim koncentracijama insulina dolazi do internalizacije membranskih lipida. Dobijeni rezultati mogu biti od značaja za pacijente obolele od šećerne bolesti i hipoglikemije.