Captopril enhanced insulin-stimulated glycogen synthesis in skeletal muscle but not fatty acid synthesis in adipose tissue of hereditary hypertriglyceridemic rats

Cahová, Monika; Vavrínková, H; Tutterová, M; Meschisvilli, Elen; Kazdová, Ludmila

doi:10.1016/s0026-0495(03)00319-6

Cited by 10 publications

(17 citation statements)

References 27 publications

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“…3A) but all groups had a similar insulin-stimulated increment of glycogen synthesis (Fig. 3B), which is a measure of skeletal muscle insulin sensitivity [36,41]. There was no difference in skeletal muscle (diaphragm) glucose oxidation (data not shown).…”

Section: Metabolic Assessmentmentioning

confidence: 87%

“…The glycogen in the heart was measured after KOH extraction [35]. Glycogen synthesis and glucose oxidation in the heart and muscle -Basal and insulinstimulated 14 C-glucose incorporation into glycogen and CO 2 was determined ex vivo in isolated diaphragm [36]. Similarly, 1-mm thick, cross-sectional slices of the left ventricle at mid-papillary level were analyzed [37].…”

Section: Systemic and Organ Metabolic Analysesmentioning

confidence: 99%

“…Low myocardial triglyceride content in ACF hearts, also reported for the first time, is probably related to limited reesterification of triglycerides due to low availability of NADPH [59] and this abnormality was unchanged by MET therapy. Although a number of works described connections between elevated levels of FFAs [16] and insulin resistance [15,60] in HF, muscle insulin sensitivity, measured as insulin-induced increment of glycogen synthesis [36,41], was preserved in ACF, making perhaps this model less prone to benefits of MET. Interestingly, fasting and postprandial insulinaemia were actually lower in ACF than in control animals.…”

Section: Metabolic Abnormalities In Acf Hf Modelmentioning

confidence: 99%

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Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

et al. 2011

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The effect of metformin therapy on cardiac function and survival in volume-overload model of heart failure in rats Short title: Metformin therapy in volume-overload heart failure in rats A c c e p t e d M a n u s c r i p t Licenced copy. Copying is not permitted, except with prior permission and as allowed by law.© 2011 The Authors Journal compilation © 2011 Portland Press Limited 2 Abstract Aims: Advanced heart failure (HF) is associated with altered substrate metabolism. Whether modification of substrate use improves the course of HF remains unknown. Antihyperglycemic drug metformin (MET) affects substrate metabolism and its use might be associated with improved outcome in diabetic HF. The aim of the study was to examine whether MET would improve cardiac function and survival also in non-diabetic HF. Methods: Volume overload HF was induced in male Wistar rats by creating aorto-caval fistula (ACF). Animals were randomized to placebo/MET (300mg/kg/day, 0.5% in food) groups and underwent assessment of metabolism, cardiovascular and mitochondrial functions (n=6-12/group) in advanced HF stage (21 st week). A separate cohort served for survival analysis (n=10-90/group). Results: The ACF group had marked cardiac hypertrophy, increased LVEDP and lung weight confirming decompensated HF, increased circulating free fatty acids (FFA), intraabdominal fat depletion, lower glycogen synthesis in the skeletal muscle (diaphragm), lower myocardial triglyceride content and attenuated myocardial 14 C-glucose and 14 C-palmitate oxidation, but preserved mitochondrial respiratory function, glucose tolerance and insulin sensitivity. MET therapy normalized serum FFA, decreased myocardial glucose oxidation, increased myocardial palmitate oxidation, but it had no effect on myocardial gene expression, AMPK signalling, ATP level, mitochondrial respiration, cardiac morphology, function and long-term survival despite reaching therapeutic serum level (2.2 ± 0.7 μg/ml). Conclusion: MET-induced enhancement of myocardial fatty acid oxidation had neutral effect on cardiac function and survival. Recently reported cardioprotective effects of MET may not be universal to all forms of HF and may require AMPK activation or ATP depletion. No increase in mortality on MET supports its safe use in diabetic HF. IntroductionAdvanced heart failure (HF) is characterized not only by a depression of heart mechanical performance but also by altered myocardial metabolism -attenuated expression of fatty acid oxidation genes [1,2] and by diminished oxidation of long chain fatty acids [1,[3][4][5], which may contribute to diminished metabolic flexibility and to energetic deficiency that further promotes worsening of HF [6]. Targeting energetic substrate metabolism might thus serve as a target for novel therapeutic approaches to HF [7,8]. Metformin (MET), a widely used antihyperglycemic drug with insulin-sensitizing properties, could be a suitable candidate for metabolic HF therapy. MET lowers serum glucose by inhibiting liver gluconeogenesis, lowers circulating free...

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Section: Metabolic Assessmentmentioning

confidence: 87%

Section: Systemic and Organ Metabolic Analysesmentioning

confidence: 99%

Section: Metabolic Abnormalities In Acf Hf Modelmentioning

confidence: 99%

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Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

et al. 2011

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“…Table 2 summarizes the potential mechanisms responsible for the beneficial effects of ACE inhibitors on skeletal muscle. ↑ glycogen storage [64] ↑ mitochondrial activity and ATP production [65] ↓ IGF-1 production [69,70] → → Improved metabolic efficiency → → Prevention of muscle loss IL-6= interleukin 6; TNF-α= tumor necrosis factor α; IGF-1= insulin-like growth factor 1…”

Section: Genetic Studiesmentioning

confidence: 99%

Effects of ACE Inhibitors on Skeletal Muscle

Onder

Vedova²,

Pahor

2006

CPD

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Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity, mortality, hospital admissions, and decline in physical function and exercise capacity in congestive heart failure (CHF) patients. These therapeutic effects are attributed primarily to beneficial cardiovascular actions of these drugs. However, it has been suggested that ACE inhibitor-induced positive effects may also be mediated by direct action on the skeletal muscle. In particular, two recently published observational studies documented that among hypertensive subjects free of CHF, treatment with ACE inhibitors was associated with better performance and muscular outcomes and genetic studies also support the hypothesis that the ACE system may be involved in physical performance and skeletal muscle function. Effects on the skeletal muscle are probably mediated by mechanical, metabolic, anti-inflammatory, nutritional, neurological and angiogenetic actions of these drugs. These studies may have major public health implications for older adults, as consequence of the fact that, in this population, gradual loss of muscle mass and muscle strength can play a key role in the onset and progression of disability. Therefore, if findings of observational studies will be later confirmed in randomized controlled trials, ACE inhibitors could represent an effective intervention to prevent physical decline in the elderly, leading to greater autonomy in this growing population.

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“…Chronic administration of ACE inhibitors [32] or of BK [33] results in a lowering of plasma free fatty acids. This result is not obtained during chronic administration of an AT1 receptor antagonist [33].…”

Section: Inhibition Of Ace Increase In Insulin Sensitivity and Kininsmentioning

confidence: 99%

The kallikrein‐kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity

Damas

Garbacki

Lefèbvre

2004

Diabetes Metabolism Res

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The therapeutic use of angiotensin converting enzyme (ACE) inhibitors, at a large scale, in arterial hypertension has showed that these molecules can exert beneficial effects on insulin sensitivity and may reduce the occurrence of type 2 diabetes mellitus. One hypothesis explaining these effects of ACE inhibitors may relate to their capacity to interfere with bradykinin (BK) metabolism and action. BK may participate in the regulation of substrate utilization by several tissues by improving blood flow and substrate delivery to the tissues and also by promoting translocation of glucose transporters. Moreover, BK has been shown to increase phosphorylation of insulin receptor and its cell substrates. BK also appears to improve the release of insulin. Furthermore, insulin may activate the kallikrein-kinin system, which consequently may increase its metabolic effects. However, in experimental diabetes mellitus, BK can participate to the inflammatory reaction leading to Langerhans islets destruction. In diabetes, whereas tissue kallikrein mRNA levels were reduced in several organs, an overexpression of kinin receptors, an increase in plasma levels of kininogens and kallikrein and an activation of the kinin system have all been reported. Lastly, kinins may be involved in the development of diabetic nephropathy. Reduction of kinin metabolism by ACE inhibitors might be involved in the beneficial effects exerted by these compounds in diabetic kidney functions.

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Captopril enhanced insulin-stimulated glycogen synthesis in skeletal muscle but not fatty acid synthesis in adipose tissue of hereditary hypertriglyceridemic rats

Cited by 10 publications

References 27 publications

Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

Effects of ACE Inhibitors on Skeletal Muscle

The kallikrein‐kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity

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