Changes in islet plasma membrane calcium-ATPase activity and isoform expression induced by insulin resistance |
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Authors: | María E Alzugaray Héctor H Del Zotto Julieta Palomeque Juan J Gagliardino Luis E Flores |
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Institution: | a CENEXA - Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata, PAHO/WHO Collaborating Center), Facultad de Ciencias Médicas, 60 y 120, 1900 La Plata, Argentina b CIC - Centro de Investigaciones Cardiovasculares (UNLP-CONICET La Plata), Facultad de Ciencias Médicas, 60 y 120, 1900 La Plata, Argentina c IQUIFIB - Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Junín 956, C1113AAD Ciudad de Buenos Aires, Argentina |
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Abstract: | We studied the effect of insulin resistance (IR) induced by administration of a fructose-rich diet (FRD) to normal Wistar rats for 21 days, upon islet plasma membrane calcium ATPases (PMCAs) and insulin secretion. FRD rats showed significantly higher triglyceride and insulin levels, insulin:glucose ratio and HOMA-IR index than controls. FRD islets released significantly more insulin in response to glucose and showed (a) marked changes in PMCA isoform protein content (decreased PMCA 2 and increased PMCA 3), (b) a decrease in total PMCAs activity, and (c) higher levels of cytosolic calcium Ca2+]i. The lower PMCAs activity with the resultant increase in Ca2+]i would favor the compensatory greater release of insulin necessary to cope with the IR state present in FRD rats and to maintain normal glucose homeostasis. Thus, changes in PMCAs activity and isoform expression play a modulatory role upon insulin secretion during long-term adaptation to an increased hormone demand. |
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Keywords: | Calcium pumps PMCAs Insulin resistance Insulin secretion PMCA isoforms Pancreatic islets |
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