Effect of Non–Insulin-Dependent Diabetes Mellitus on Myocardial Insulin Responsiveness in Patients With Ischemic Heart Disease

Jagasia, Dinesh; Whiting, Jennifer M.; Concato, John; Pfau, Steven; McNulty, Patrick H.

doi:10.1161/01.cir.103.13.1734

Cited by 84 publications

(67 citation statements)

References 29 publications

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“…We previously observed that physiological hyperinsulinemia modestly increased coronary blood flow in subjects without diabetes (43), but that this effect was absent in patients with Type 2 diabetes who were studied under hyperglycemic conditions (20). In the present study, a 1-h glucose infusion induced endogenous insulin secretion.…”

Section: Discussionsupporting

confidence: 38%

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Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients

McNulty

Tulli

Robertson

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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McNulty PH, Tulli MA, Robertson BJ, Lendel V, Harach LA, Scott S, Boehmer JP. Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients. Am J Physiol Heart Circ Physiol 293: H103-H108, 2007. First published March 16, 2007; doi:10.1152/ajpheart.00779.2006.-Patients with diabetes mellitus exhibit postprandial hyperglycemia, systemic oxidative stress, impaired endothelium-dependent, nitric oxide (NO)-mediated coronary artery dilatation, and an increased incidence of coronary events. Whether hyperglycemia causally mediates these associations is unknown. To test the hypothesis that postprandial hyperglycemia acutely impairs coronary endothelial function in humans, we compared the ability of the endothelium-dependent vasodilator acetylcholine to increase conduit coronary diameter (the macrovascular response) and coronary blood flow velocity (the microvascular response) in 12 cardiac transplant recipients without diabetes before and after blood glucose was raised from 6.7 Ϯ 1.3 mmol/l (121 Ϯ 24 mg/dl) to 17.8 Ϯ 1.5 mmol/l (321 Ϯ 27 mg/dl) for 1 h. Hyperglycemia acutely doubled circulating levels of the oxidation product malondialdehyde, indicating systemic oxidative stress, but did not affect the ability of acetylcholine to dilate conduit coronary segments or accelerate coronary blood flow. We conclude that the oxidative stress associated with a single acute episode of hyperglycemia affects neither acetylcholine-mediated coronary endothelial NO release nor the subsequent bioavailability, metabolism, or action of NO within the coronary circulation of cardiac transplant recipients. These observations imply that the relationship among hyperglycemia, oxidative stress, and coronary endothelial dysfunction is presumably mediated by mechanisms operating over longer periods of time. diabetes mellitus; coronary artery; coronary endothelial dysfunction ONE OF THE EARLIEST ABNORMALITIES identified in both animal models of diabetes mellitus (29, 34) and humans with the disease (31, 32, 37) is impairment in the ability of the coronary endothelium to effect nitric oxide (NO)-mediated arterial dilatation. Several lines of evidence suggest this may be mediated by hyperglycemia. Hyperglycemia is the hallmark of diabetes and one of its earliest features. In vitro, hyperglycemia accelerates glucose consumption by endothelial cells resulting in cytosolic accumulation of diacylglycerol, activation of protein kinase C, and inhibition of endothelial NO synthase (eNOS) (12,43). Hyperglycemia also fuels the formation of reactive oxygen species (ROS) and of advanced glycosylation end products of endovascular proteins, both of which quench NO in vitro (5, 26). Perfusing the isolated rat heart with hyperglycemic solution for 1 h accelerates venous washout of nitrotyrosine (a byproduct of the reaction of ROS with NO) and increases coronary vascular resistance (9). Hyperglycemia may also stimulate the elaboration of substances [e.g., endothelin-1 (24, 35), tumor necrosis factor-␣ (11, 30)], which indirec...

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Section: Discussionsupporting

confidence: 38%

“…Hyperglycemic patients with diabetes mellitus exhibit impaired endothelium-dependent vasodilatation in both the pe- ripheral (21,44) and coronary (20,37,43) circulation. Longitudinal studies have demonstrated this impairment to be associated with a substantially increased risk of adverse coronary events (2).…”

Section: Discussionmentioning

confidence: 99%

Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients

McNulty

Tulli

Robertson

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…Some studies have not observed IR in hearts of type II diabetic patients, even when other diabetic tissues of the same patients exhibit significant IR (Utriainen et al, 1998;Jagasia et al, 2001). Thus under conditions of diabetic hyperinsulinemia, the less-resistant heart is being stimulated by relatively high levels of insulin.…”

Section: Discussionmentioning

confidence: 99%

Impact of L-Carnitine and Cinnamon on Insulin-Like Growth Factor-1 and Inducible Nitric Oxide Synthase Gene Expression in Heart and Brain of Insulin Resistant Rats

Mohamed¹

2010

American Journal of Biochemistry and Biotechnology

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Problem statement: Evaluate the effects of daily administration of L-carnitine and cinnamon extract for two weeks on the expression of Insulin-like Growth Factor-1 (IGF-1) and inducible Nitric Oxide Synthase (iNOS) genes in cardiac and brain tissues of rats with Insulin Resistance (IR). Approach: Rats were divided into 4 groups (8 animals each): Group (1) rats fed control diet (60% starch) as control while groups (2, 3 and 4) fed high fructose diet (60% fructose). At the beginning of the 3rd week of feeding, rats of group (3) were treated with L-carnitine (300 mg kg −1 body weight/day, i.p.) and animals of group (4) received a daily oral dose of cinnamon aqueous extract (0.5 mL rat −1 ). The animals were maintained in their respective groups for 4 weeks. Results:Feeding high fructose diet causes significant reduction in Insulin Receptor Substrate-1 (IRS-1) (amounted 30.65%) and elevation in iNOS expression (reached 51%) in the cardiac tissues as compared to control. In brain tissues, the IGF-1 mRNA was reduced in fructose loaded groups (28.81%). Administration of either L-carnitine or cinnamon extract significantly improves the expression of the cardiac studied genes but with no effects on the brain tissues. Conclusion: The present study illustrated that CE was more potent than L-carnitine in improving the IR.Key word: Insulin resistance, insulin-like growth factor-1, inducible nitric oxide synthase, insulin receptor substrate-1

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“…Insulin may also increase cardiac contractility (13) and may have an antiapoptotic effect on cardiomyocytes (14). In vivo, many of the effects of insulin on cardiac metabolism and function are related to the systemic effects of insulin, such as increased peripheral and coronary vasodilatation (15,16), increased sodium and water uptake by the kidneys (17), and changes in the delivery of substrates to the heart (18). For example, insulin's antilipolytic effect will reduce the delivery of FFAs to the heart, which, in concert with increased intracellular malonyl coenzyme A (CoA) levels, reduce fatty acid oxidation rates (19).…”

Section: Introductionmentioning

confidence: 99%

“…The increase in myocardial glucose oxidation observed after insulin stimulation was unexpected and indicates, for the first time to our knowledge, that the ability of insulin to increase glucose oxidation in heart muscle might not be mediated by insulin receptors in the cardiomyocyte. Insulin receptors are present in the vascular endothelium (56), and insulin has been shown to be a potent vasodilator of the coronary vascular bed (16). Indeed, coronary flow was significantly higher in insulin-treated CIRKO animals than in controls.…”

mentioning

confidence: 99%

Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression

Belke¹,

Bétuing²,

Tuttle³

et al. 2002

J. Clin. Invest.

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Effect of Non–Insulin-Dependent Diabetes Mellitus on Myocardial Insulin Responsiveness in Patients With Ischemic Heart Disease

Cited by 84 publications

References 29 publications

Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients

Effect of simulated postprandial hyperglycemia on coronary blood flow in cardiac transplant recipients

Impact of L-Carnitine and Cinnamon on Insulin-Like Growth Factor-1 and Inducible Nitric Oxide Synthase Gene Expression in Heart and Brain of Insulin Resistant Rats

Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression

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