TY - JOUR
T1 - Impaired cardiac function and IGF-I response in myocytes from calmodulin-diabetic mice
T2 - Role of Akt and RhoA
AU - Duan, Jinhong
AU - Zhang, Hai-Ying
AU - Adkins, Steven D.
AU - Ren, Bonnie H.
AU - Norby, Faye L.
AU - Zhang, Xiaochun
AU - Benoit, Joseph N.
AU - Epstein, Paul N.
AU - Ren, Jun
PY - 2003/2/1
Y1 - 2003/2/1
N2 - This study characterized the cardiac contractile function and IGF-I response in a transgenic diabetic mouse model. Mechanical properties were evaluated in cardiac myocytes from OVE26 diabetic and FVB wild-type mice, including peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90) and maximal velocity of shortening/relengthening (textpmdL/dt). Intracellular Ca2+ was evaluated as Ca2+-induced Ca2+ release [difference in fura 2 fluorescent intensity (ΔFFI)] and fluorescence decay rate (τ). Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a, phospholamban (PLB), Na+-Ca2+ exchanger (NCX), GLUT4, and the serine-threonine kinase Akt were assessed by Western blot. RhoA and IGF-I/IGF-I receptor mRNA levels were determined by RT-PCR and Northern blot. OVE26 myocytes displayed decreased PS, textpmdL/dt, and ΔFFI associated with prolonged TPS, TR90, and τ. SERCA2a, NCX, and Akt activation were reduced, whereas PLB and RhoA were enhanced in OVE26 hearts. GLUT4 was unchanged. IGF-I enhanced PS and ΔFFI in FVB but not OVE26 myocytes. IGF-I mRNA was increased, but IGF-I receptor mRNA was reduced in OVE26 hearts and livers. These results validate diabetic cardiomyopathy in OVE26 mice due to reduced SERCA2, NCX, IGF-I response, and Akt activation associated with enhanced RhoA level, suggesting a therapeutic potential for Akt and RhoA.
AB - This study characterized the cardiac contractile function and IGF-I response in a transgenic diabetic mouse model. Mechanical properties were evaluated in cardiac myocytes from OVE26 diabetic and FVB wild-type mice, including peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90) and maximal velocity of shortening/relengthening (textpmdL/dt). Intracellular Ca2+ was evaluated as Ca2+-induced Ca2+ release [difference in fura 2 fluorescent intensity (ΔFFI)] and fluorescence decay rate (τ). Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a, phospholamban (PLB), Na+-Ca2+ exchanger (NCX), GLUT4, and the serine-threonine kinase Akt were assessed by Western blot. RhoA and IGF-I/IGF-I receptor mRNA levels were determined by RT-PCR and Northern blot. OVE26 myocytes displayed decreased PS, textpmdL/dt, and ΔFFI associated with prolonged TPS, TR90, and τ. SERCA2a, NCX, and Akt activation were reduced, whereas PLB and RhoA were enhanced in OVE26 hearts. GLUT4 was unchanged. IGF-I enhanced PS and ΔFFI in FVB but not OVE26 myocytes. IGF-I mRNA was increased, but IGF-I receptor mRNA was reduced in OVE26 hearts and livers. These results validate diabetic cardiomyopathy in OVE26 mice due to reduced SERCA2, NCX, IGF-I response, and Akt activation associated with enhanced RhoA level, suggesting a therapeutic potential for Akt and RhoA.
KW - Diabetic mouse
KW - Excitation-contraction coupling
KW - Insulin-like growth factor I
KW - Sarco(endo)plasmic reticulum Ca-ATPase
KW - Sodium-calcium exchanger
KW - Ventricular myocyte
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UR - http://www.scopus.com/inward/citedby.url?scp=0037304190&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.00254.2002
DO - 10.1152/ajpendo.00254.2002
M3 - Article
C2 - 12531745
AN - SCOPUS:0037304190
SN - 0193-1849
VL - 284
SP - E366-E376
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 2
ER -
