Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling

Malfitano, Christiane; Souza, Adriano Lopes de; Carbonaro, Mariana; Lopes, Andressa Bolsoni; Figueroa, Diego; Souza, Leandro Franco de; Silva, Kleiton Augusto Santos; Consolim‐Colombo, Fernanda Marciano; Curi, Rui; Irigoyen, Maria Cláudia

doi:10.1186/s12933-015-0308-y

Cited by 35 publications

(36 citation statements)

References 52 publications

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“…The models are used not only to study pathological consequences of DM, but also to evaluate experimental approaches for the treatment of this condition [37]. As previously reported [61–63], streptozotocin-induced diabetes mellitus is characterized by body weight loss and increased blood glucose. Despite the lower final body weight in diabetic rats, blood pressure did not differ between groups.…”

Section: Discussionmentioning

confidence: 99%

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Rosa¹,

Gimenes²,

Campos³

et al. 2016

Cardiovasc Diabetol

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PurposeAlthough increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM).MethodsMale SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann–Whitney.ResultsEchocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups.ConclusionApocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.

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Section: Discussionmentioning

confidence: 99%

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Rosa¹,

Gimenes²,

Campos³

et al. 2016

Cardiovasc Diabetol

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“…In the diabetic heart, glucose oxidation is inhibited at multiple steps: (i) uptake of glucose is inhibited by reduced expression of glucose transporter Glut4 as well as by blunted translocation of Glut4 in response to insulin (64, 65); (ii) inhibition of hexokinase activity by fatty acids (FAs) resulting in reduced conversion of glucose to glucose-6-phosphate (80); (iii) inhibition of phosphofructokinase activity by FA, leading to reduced formation of fructose-1,6-bisphosphate by fructose-6-phosphate (69); (iv) inhibition of pyruvate dehydrogenase phosphatase activity by FA resulting in reduced pyruvate dehydrogenase (PDH) activity, which leads to reduced conversion of pyruvate to acetyl CoA. In the diabetic heart, PPARα expression is activated by increased FA uptake (81, 82).…”

Section: Decreased Glucose Uptake and Metabolismmentioning

confidence: 99%

Diabetic Cardiomyopathy: An Immunometabolic Perspective

et al. 2017

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The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM. These early events are followed by steatosis (accumulation of lipid droplets) in cardiomyocytes, which is followed by apoptosis, changes in immune responses with a consequent increase in fibrosis, remodeling of cardiomyocytes, and the resultant decrease in cardiac function. The heart is an omnivore, metabolically flexible, and consumes the highest amount of ATP in the body. Altered myocardial substrate and energy metabolism initiate the development of DCM. Diabetic hearts shift away from the utilization of glucose, rely almost completely on fatty acids (FAs) as the energy source, and become metabolically inflexible. Oxidation of FAs is metabolically inefficient as it consumes more energy. In addition to metabolic inflexibility and energy inefficiency, the diabetic heart suffers from impaired calcium handling with consequent alteration of relaxation–contraction dynamics leading to diastolic and systolic dysfunction. Sarcoplasmic reticulum (SR) plays a key role in excitation–contraction coupling as Ca2+ is transported into the SR by the SERCA2a (sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a) during cardiac relaxation. Diabetic cardiomyocytes display decreased SERCA2a activity and leaky Ca2+ release channel resulting in reduced SR calcium load. The diabetic heart also suffers from marked downregulation of novel cardioprotective microRNAs (miRNAs) discovered recently. Since immune responses and substrate energy metabolism are critically altered in diabetes, the present review will focus on immunometabolism and miRNAs.

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“…It is widely accepted that STZ toxic to the beta cells of the pancreas and damages insulin production [25]. STZ not only reduces insulin receptor signaling and downstream proteins, including IRS‐1, IRS‐2, AMPK, and GLUT [26], but also influences glycolysis proteins, including GCK and PPAR‐γ [27–29], by activating the MAPKs pathway [29,30]. STZ increases reactive oxygen species (ROS), nitric oxide production, oxidative stress and mitochondrial dysfunction [30,31] to induce damage to pancreas beta cells [32], while the MAPKs pathway can be stimulated by ROS and oxidative stress [30–32].…”

Section: Discussionmentioning

confidence: 99%

Eugenosedin‐A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide‐induced diabetic rats

Shen

Lin

Yen

et al. 2017

The Kaohsiung J of Med Scie

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This study examined the effects of eugenosedin-A (Eu-A) in a streptozotocin (STZ)/nicotinamide-induced rat model of type II diabetes mellitus (T2DM). Six-week-old Sprague-Dawley rats were randomly divided into three groups: (1) RD group, normal rats fed a regular diet (RD), (2) DM group, T2DM rats fed a high-fat diet, and (3) Eu-A group, T2DM rats fed a high fat diet plus oral Eu-A (5 mg/kg/day). After 30 days, the DM group had higher body weight, higher blood glucose and lower insulin levels than the RD group. The DM group also had increased protein expression of glycogen synthase kinase (GSK) in liver and skeletal muscle and decreased protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), IRS-2, AMP-activated protein kinase (AMPK), glucose transporter-4 (GLUT-4), glucokinase (GCK), and peroxisome proliferator-activated receptor γ (PPAR-γ). STZ/nicotinamide-induced T2DM increased the expression of mitogen-activated protein kinases (MAPKs: p38, ERK, JNK) and inflammatory p65 protein. In the Eu-A treated T2DM rats, however, blood glucose was attenuated and the insulin concentration stimulated. Changes in IR, IRS-1 and IRS-2 proteins as well as AMPK, GLUT-4, GCK, GSK, PPAR-γ, MAPKs, and inflammatory p65 proteins were ameliorated. These results suggested that Eu-A alleviates STZ/nicotinamide-induced hyperglycemia by improving insulin levels and glucose metabolism, and inhibiting the MAPKs- and p65-mediated inflammatory pathway.

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Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling

Cited by 35 publications

References 52 publications

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus

Diabetic Cardiomyopathy: An Immunometabolic Perspective

Eugenosedin‐A improves glucose metabolism and inhibits MAPKs expression in streptozotocin/nicotinamide‐induced diabetic rats

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