Changes in islet plasma membrane calcium-ATPase activity and isoform expression induced by insulin resistance.
We studied the effect of insulin resistance (IR) induced by administration of a fructose-rich diet (FRD) to normal Wistar rats for 21days, 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 [Ca(2+)](i). The lower PMCAs activity with the resultant increase in [Ca(2+)](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.
Alzugaray
María E
ME
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.
García
María E
ME
Del Zotto
Héctor H
HH
Raschia
María A
MA
Palomeque
Julieta
J
Rossi
Juan P F C
JP
Gagliardino
Juan J
JJ
Flores
Luis E
LE
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000378:metabolism; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D004040:Dietary Carbohydrates; D007328:Insulin; D007527:Isoenzymes; D012333:RNA, Messenger; D014280:Triglycerides; D005632:Fructose; D053499:Plasma Membrane Calcium-Transporting ATPases; D005947:Glucose; D002118:Calcium