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International Journal of Experimental Diabetes Research - Volume 1 2000, Issue 4, Pages 275-287

Center for Biotechnology, Anna University, Chennai 600025, India

Madras Diabetes Research Foundation, Gopalapuram, Chennai 600086, India

Madras Diabetes Research Foundation MDRF, 35, Conran Smith Road, Gopalapuram, Chennai 600086, India

Received 8 November 1999; Accepted 17 June 2000

Copyright © 2000 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Altered cytosolic Ca2+ is implicated in the aetiologyof many diseases including diabetes but there arefew studies on the mechanisms of the altered Ca2+regulation. Using human lymphocytes, we studiedcytosolic calcium Cai and various Ca2+ transportmechanisms in subjects with Type 2 diabetesmellitus and control subjects. Ca2+-specific fluorescentprobes Fura-2 and Fluo-3 were used tomonitor the Ca2+ signals. Thapsigargin, a potent andspecific inhibitor of the sarcoendoplasmic reticulumCa2+-ATPase SERCA, was used to study Ca2+-store dependent Ca2+ fluxes. Significant P < 0.05elevation of basal Cai levels was observed inlymphocytes from diabetic subjects. Cai levels werepositively correlated with fasting, plasma glucoseand HbAlc. There was also a significant P < 0.05reduction in plasma membrane calcium PMCAATPase activity in diabetic subjects compared tocontrols. Cells from Type 2 diabetics exhibited anincreased Ca2+ influx as measured both by Fluo-3fliorescence and C45a assays as a consequence ofof thapsigargin-mediated Ca2+ store depletion. Uponaddition of Mn2+ a surrogate of Ca2+, the fura-2fluorescence decayed in an exponential fashion andthe rate and extent of this decline was steeper andgreater in cells from type 2 diabetic patients. Therewas also a significant P < 0.05 difference in theNa+-Ca2+ exchange activity in Type 2 diabeticpatients, both under resting conditions and after challenging the cells with thapsigargin, when theinternal store Ca2+ sequestration was circumvented.Pharmacological activation of protein kinase CPKC in cells from patients resulted in only partialinhibition of Ca2+ entry. We conclude that cellularCa2+ accumulation in cells from Type 2 diabetesresults from a reduction in PMCA ATPase activity,b modulation of Na+-Ca2+ exchange and 3increased Ca2+ influx across the plasma membrane.

Autor: Muthuswamy Balasubramanyam, Ramalingham A. Balaji, Balakrishnan Subashini, and Viswanathan Mohan

Fuente: https://www.hindawi.com/


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