Modulation of erythrocyte ghost membrane Ca²⁺-pumping atpase of healthy and non-insulin dependent diabetic humans by alpha, alpha trehalose-6- phosphate and extracts of <i>Carica papaya</i> Linn.

Abstract

Background: Although glycosylated Ca²⁺- ATPase has not been demonstrated in diabetes mellitus, but it is evident that the enzyme can be significantly glycated under experimental conditions in the presence of appreciable high levels of glucose.

Objective: In this study, the hypoglycaemic agents Trehalose-6-phosphate derivative (Tp) and mature but unripe fruits of Carica papaya L (Cp) were used to modulate the activity of the erythrocyte ghost membrane (EGM) Ca²⁺ pumping ATPase of healthy and non-insulin dependent diabetes mellitus (NIDDM) individuals.

Results: The Ca²⁺- pumping ATPase in membrane of healthy and NIDDM individuals was activated maximally by 2.5mg/ml (2.6 folds) and 4mg/ml (1.7 folds) of the crude extracts of Cp respectively, while 3mg/ml of Tp optimally stimulated the membrane-bound enzyme in both healthy (2.1 folds) and NIDDM (1.5 folds) individuals, respectively. The NIDDM enzyme is less active with a lower affinity for the substrate (30.6±2.52 μMol ATP) compared to healthy individuals (21.5 ± 2.15 μMol ATP), whereas, exposure of the NIDDM Ca²⁺- pumping ATPase to Tp (3mg/ml) or Cp (4mg/ml), increased the affinity of the enzyme for ATP to 22.4±2.32μMol ATP and 22.1±2.22μMol ATP, respectively.

Conclusion: These findings suggest that Cp and Tp could therapeutically not only lower blood glucose levels as hypoglycaemic agents but could also attenuate the elevated Ca²⁺ concentration implicated in diabetes mellitus.

Keywords: Diabetes mellitus, Calcium-ATPase, Carica papaya, Trehalose-6-phosphate