IGF-I attenuates diabetes-induced cardiac contractile dysfunction in ventricular myocytes

Faye L. Norby, Loren E. Wold, Jinhong Duan, Kadon K. Hintz, Jun Ren

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76 Scopus citations

Abstract

Diabetic cardiomyopathy is characterized by impaired ventricular contraction and altered function of insulin-like growth factor I (IGF-I), a key factor for cardiac growth and function. Endogenous IGF-I has been shown to alleviate diabetic cardiomyopathy. This study was designed to evaluate exogenous IGF-I treatment on the development of diabetic cardiomyopathy. Adult rats were divided into four groups: control, control + IGF-I, diabetic, and diabetic + IGF-I. Streptozotocin (STZ; 55 mg/kg) was used to induce experimental diabetes immediately followed by a 7-wk IGF-I (3 mg·kg-1·day-1 ip) treatment. Mechanical properties were assessed in ventricular myocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocities of shortening/relengthening (±dL/dt). Intracellular Ca2+ transients were evaluated as Ca2+-induced Ca2+ release and Ca2+ clearing constant. Levels of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and glucose transporter (GLUT4) were assessed by Western blot. STZ caused significant weight loss and elevated blood glucose, demonstrating the diabetic status. The diabetic state is associated with reduced serum IGF-I levels, which were restored by IGF-I treatment. Diabetic myocytes showed reduced PS and ±dL/dt as well as prolonged TPS, TR90, and intracellular Ca2+ clearing compared with control. IGF-I treatment prevented the diabetes-induced abnormalities in PS, ±dL/dt, TR90, and Ca2+ clearing but not TPS. The levels of SERCA and GLUT4, but not PLB, were significantly reduced in diabetic hearts compared with controls. IGF-I treatment restored the diabetes-induced decline in SERCA, whereas it had no effect on GLUT4 and PLB levels. These results suggest that exogenous IGF-I treatment may ameliorate contractile disturbances in cardiomyocytes from diabetic animals and could provide therapeutic potential in the treatment of diabetic cardiomyopathy.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume283
Issue number4 46-4
StatePublished - Oct 2002
Externally publishedYes

Keywords

  • Diabetic cardiomyopathy
  • Glucose transporter 4
  • Insulin-like growth factor I
  • Sarco(endo)plasmic reticulum Ca-ATPase
  • Ventricular myocytes

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