Abstract |
Diabetic cardiomyopathy is characterized by cardiac dysfunction and altered level/function of insulin-like growth factor I ( IGF-I). Both endogenous and exogenous IGF-I have been shown to effectively alleviate diabetes-induced cardiac dysfunction and oxidative stress. This study was designed to examine the effect of cardiac overexpression of IGF-I on streptozotocin (STZ)-induced cardiac contractile dysfunction in mouse myocytes. Both IGF-I heterozygous transgenic mice and their wild-type FVB littermates were made diabetic with a single injection of STZ (200 mg/kg, i.p.) and maintained for 2 weeks. The following mechanical indices were evaluated in ventricular myocytes: peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening/relengthening (+/- dL/dt). Intracellular Ca2+ was evaluated as resting and peak intracellular Ca2+ levels, Ca2+-induced Ca2+ release and intracellular Ca2+ decay rate (tau). STZ led to hyperglycemia in FVB and IGF-I mice. STZ treatment prolonged TPS and TR90, reduced Ca2+-induced Ca2+ release, increased resting intracellular Ca2+ levels and slowed tau associated with normal PS and +/- dL/dt. All of which, except the elevated resting intracellular Ca2+, were prevented by the IGF-I transgene. In addition, myocytes from STZ-treated FVB mice displayed an attenuated contractile response to the beta-adrenergic agonist isoproterenol, which was restored by the IGF-I transgene. Contractile response to the alpha-adrenergic agonist phenylephrine and angiotensin II was not affected by either STZ treatment or IGF-I. These results validate the beneficial role of IGF-I in diabetic cardiomyopathy, possibly due to an improved beta- adrenergic response.
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Authors | F L Norby, N S Aberle 2nd, J Kajstura, P Anversa, J Ren |
Journal | The Journal of endocrinology
(J Endocrinol)
Vol. 180
Issue 1
Pg. 175-82
(Jan 2004)
ISSN: 0022-0795 [Print] England |
PMID | 14709156
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Adrenergic alpha-Agonists
- Adrenergic beta-Agonists
- Angiotensin II
- Phenylephrine
- Insulin-Like Growth Factor I
- Isoproterenol
- Calcium
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Topics |
- Adrenergic alpha-Agonists
(pharmacology)
- Adrenergic beta-Agonists
(pharmacology)
- Angiotensin II
(pharmacology)
- Animals
- Body Weight
- Calcium
(metabolism)
- Cells, Cultured
- Diabetes Mellitus, Experimental
(metabolism, physiopathology)
- Gene Expression
- Heart Ventricles
- Insulin-Like Growth Factor I
(genetics)
- Isoproterenol
(pharmacology)
- Male
- Mice
- Mice, Inbred Strains
- Mice, Transgenic
- Models, Animal
- Myocardial Contraction
(drug effects)
- Myocardium
(pathology)
- Myocytes, Cardiac
(metabolism)
- Organ Size
- Phenylephrine
(pharmacology)
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