| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print June 25, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00003.2002
Submitted on January 7, 2002
Accepted on June 19, 2002
1 Pharmacology, Physiology, and Therapeutics, University of North Dakota, Grand Forks, ND, USA
* To whom correspondence should be addressed. E-mail: jren{at}medicine.nodak.edu.
Diabetic cardiomyopathy is characterized by impaired ventricular contraction and altered function of insulin-like growth factor-1 (IGF-1), a key factor for cardiac growth and function. Endogenous IGF-1 has been shown to alleviate diabetic cardiomyopathy. This study was designed to evaluate exogenous IGF-1 treatment on the development of diabetic cardiomyopathy. Adult rats were divided into four groups: control, control + IGF-1, diabetic and diabetic + IGF-1. Streptozotocin (STZ, 55mg/kg) was used to induce experimental diabetes immediately followed by a 7-week IGF-1 (3 mg/kg/d, i.p.) 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-1 levels, which was restored by IGF-1 treatment. Diabetic myocytes showed reduced PS and ± dL/dt as well as prolonged TPS, TR90 and intracellular Ca2+ clearing compared to control. IGF-1 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 to controls. IGF-1 treatment restored the diabetes-induced decline in SERCA whereas it had no effect on GLUT4 and PLB levels. These results suggest that exogenous IGF-1 treatment may ameliorate contractile disturbances in cardiomyocytes from diabetic animals and could provide therapeutic potential in the treatment of diabetic cardiomyopathy.
This article has been cited by other articles:
|
|
 |
|
  J. Ren, J. Duan, D. P. Thomas, X. Yang, N. Sreejayan, J. R. Sowers, A. Leri, J. Kajstura, F. Gao, and P. Anversa IGF-I alleviates diabetes-induced RhoA activation, eNOS uncoupling, and myocardial dysfunction Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R793 - R802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-F. Yeih, L.-Y. Lin, H.-I Yeh, Y.-J. Lai, F.-T. Chiang, C.-D. Tseng, S.-H. Chu, and Y.-Z. Tseng Temporal changes in cardiac force- and flow-generation capacity, loading conditions, and mechanical efficiency in streptozotocin-induced diabetic rats Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H867 - H874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Ceylan-Isik, K. H. LaCour, and J. Ren Sex difference in cardiomyocyte function in normal and metallothionein transgenic mice: the effect of diabetes mellitus J Appl Physiol, May 1, 2006; 100(5): 1638 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Bidasee, Y. Zhang, C. H. Shao, M. Wang, K. P. Patel, U. D. Dincer, and H. R. Besch Diabetes Increases Formation of Advanced Glycation End Products on Sarco(endo)plasmic Reticulum Ca2+-ATPase Diabetes, February 1, 2004; 53(2): 463 - 473. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. R. Privratsky, L. E. Wold, J. R. Sowers, M. T. Quinn, and J. Ren AT1 Blockade Prevents Glucose-Induced Cardiac Dysfunction in Ventricular Myocytes: Role of the AT1 Receptor and NADPH Oxidase Hypertension, August 1, 2003; 42(2): 206 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ren, J. Duan, K. K Hintz, and B. H Ren High glucose induces cardiac insulin-like growth factor I resistance in ventricular myocytes: role of Akt and ERK activation Cardiovasc Res, March 1, 2003; 57(3): 738 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Duan, H.-Y. Zhang, S. D. Adkins, B. H. Ren, F. L. Norby, X. Zhang, J. N. Benoit, P. N. Epstein, and J. Ren Impaired cardiac function and IGF-I response in myocytes from calmodulin-diabetic mice: role of Akt and RhoA Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E366 - E376. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
