Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart

Desrois, Martine; Sidell, Robert J.; Guyader, Dominique; King, Linda M.; Radda, George K.; Clarke, Kieran

doi:10.1016/j.cardiores.2003.11.021

Cited by 110 publications

(83 citation statements)

References 45 publications

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“…Finally, cardiac samples from patients with heart failure in which Akt is activated (11) also demonstrated a reduction in IRS-1. Moreover, these data are consistent with evidence that cardiac IRS-1 is decreased in type 2 diabetes (26,27), which possibly represents a response to chronic hyperinsulinemia and contributes to the development of insulin resistance in this setting. Prior studies in other systems have also demonstrated that serine or threonine phosphorylation of IRS-1 mediated by a variety of kinases including inhibitor of kB kinase (IKK) (28,29), PKC (30, 31), JNK (32), p70S6 kinase (33), and Akt (21) can inhibit PI3K activation through either reduced IRS-1/PI3K association or degradation.…”

Section: Figuresupporting

confidence: 89%

PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury

Nagoshi¹,

Mizutani²,

Aoyama³

et al. 2005

J. Clin. Invest.

218

182

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Acute activation of the serine-threonine kinase Akt is cardioprotective and reduces both infarction and dysfunction after ischemia/reperfusion injury (IRI). However, less is known about the chronic effects of Akt activation in the heart, and, paradoxically, Akt is activated in samples from patients with chronic heart failure. We generated Tg mice with cardiac-specific expression of either activated (

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Section: Figuresupporting

confidence: 89%

PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury

Nagoshi¹,

Mizutani²,

Aoyama³

et al. 2005

J. Clin. Invest.

218

182

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show abstract

“…Fein et al, 1985;Zola et al, 1988 BB rat Rodrigues and McNeill, 1990;Broderick and Hutchison, 2004;Broderick and Poirier, 2005 Type 2 diabetes Goto-Kakizaki rat Desrois et al, 2004a;Desrois et al, 2004b KK A y mouse Ye et al, 2004 NOD, non-obese diabetic.…”

Section: The Ove26 Mouse Modelmentioning

confidence: 99%

Rodent models of diabetic cardiomyopathy

Bugger

Abel

2009

Disease Models &Amp; Mechanisms

247

198

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Diabetic cardiomyopathy increases the risk of heart failure in individuals with diabetes, independently of co-existing coronary artery disease and hypertension. The underlying mechanisms for this cardiac complication are incompletely understood. Research on rodent models of type 1 and type 2 diabetes, and the use of genetic engineering techniques in mice, have greatly advanced our understanding of the molecular mechanisms responsible for human diabetic cardiomyopathy. The adaptation of experimental techniques for the investigation of cardiac physiology in mice now allows comprehensive characterization of these models. The focus of the present review will be to discuss selected rodent models that have proven to be useful in studying the underlying mechanisms of human diabetic cardiomyopathy, and to provide an overview of the characteristics of these models for the growing number of investigators who seek to understand the pathology of diabetes-related heart disease.

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“…Studies investigating cardiovascular changes in Type 2 diabetic rats have employed spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF), Goto-Kakizaki (GK), and Zucker Diabetic Fatty (ZDF) rats [8][9][10][11][12]. A spontaneous Type 2 diabetic rat BBZDR/Wor (BBZ), from Biomedical Research Models (Worcester, MA) has been shown to closely mimic human disease.…”

Section: Introductionmentioning

confidence: 99%

Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

Hwang

Ananthakrishnan

et al. 2008

Cardiovasc Diabetol

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We investigated the role of polyol pathway enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH) in mediating injury due to ischemia-reperfusion (IR) in Type 2 diabetic BBZ rat hearts. Specifically, we investigated, (a) changes in glucose flux via cardiac AR and SDH as a function of diabetes duration, (b) ischemic injury and function after IR, (c) the effect of inhibition of AR or SDH on ischemic injury and function. Hearts isolated from BBZ rats, after 12 weeks or 48 weeks diabetes duration, and their non-diabetic littermates, were subjected to IR protocol. Myocardial function, substrate flux via AR and SDH, and tissue lactate:pyruvate (L/P) ratio (a measure of cytosolic NADH/NAD + ), and lactate dehydrogenase (LDH) release (a marker of IR injury) were measured. Zopolrestat, and CP-470,711 were used to inhibit AR and SDH, respectively. Myocardial sorbitol and fructose content, and associated changes in L/P ratios were significantly higher in BBZ rats compared to non-diabetics, and increased with disease duration. Induction of IR resulted in increased ischemic injury, reduced ATP levels, increases in L/P ratio, and poor cardiac function in BBZ rat hearts, while inhibition of AR or SDH attenuated these changes and protected hearts from IR injury. These data indicate that AR and SDH are key modulators of myocardial IR injury in BBZ rat hearts and that inhibition of polyol pathway could in principle be used as a therapeutic adjunct for protection of ischemic myocardium in Type 2 diabetic patients.

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Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart

Abstract: We conclude that decreased insulin receptor beta, IRS-1 and GLUT4 proteins are associated with insulin resistance in type 2 diabetic rat hearts.

Cited by 110 publications

References 45 publications

PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury

PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury

Rodent models of diabetic cardiomyopathy

Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

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