Activation of IGF-1 receptors and Akt signaling by systemic hyperinsulinemia contributes to cardiac hypertrophy but does not regulate cardiac autophagy in obese diabetic mice

Pires, Karla Maria Pereira; Buffolo, Márcio; Schaaf, Christin; Symons, J. David; Cox, James E.; Abel, E. Dale; Selzman, Craig H.; Boudina, Sihem

doi:10.1016/j.yjmcc.2017.10.001

Cited by 31 publications

(26 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to study cardiac function independently of the effect of obesity [17], hyperinsulinemia [18] and high-glycemic load [19], we selected animals within each sex group that had similar body weight as well as normal insulin and FBG levels (Fig 1). Only one male in the Chow group had borderline high FBG value (6.4 mmol l -1 , compared with 5.6 mmol l -1 threshold).…”

Section: Resultsmentioning

confidence: 99%

Cardiovascular sexual dimorphism in a diet-induced type 2 diabetes rodent model, the Nile rat (Arvicanthis niloticus)

et al. 2018

View full text Add to dashboard Cite

BackgroundThe Nile rat (Arvicanthis niloticus) is an emerging laboratory model of type 2 diabetes. When fed standard rodent chow, the majority of males progress from hyperinsulinemia by 2 months to hyperglycemia by 6 months, while most females remain at the hyperinsulinemia-only stage (prediabetic) from 2 months onward. Since diabetic cardiomyopathy is the major cause of type-2 diabetes mellitus (T2DM)-related mortality, we examined whether sexual dimorphism might entail cardiac functional changes. Our ultimate goal was to isolate the effect of diet as a modifiable lifestyle factor.Materials and methodsNile rats were fed either standard rodent chow (Chow group) or a high-fiber diet previously established to prevent type 2 diabetes (Fiber group). Cardiac function was determined with echocardiography at 12 months of age. To isolate the effect of diet alone, only the small subset of animals resistant to both hyperinsulinemia and hyperglycemia were included in this study.ResultsIn males, Chow (compared to Fiber) was associated with elevated heart rate and mitral E/A velocity ratio, and with lower e’-wave velocity, isovolumetric relaxation time, and ejection time. Of note, these clinically atypical types of diastolic dysfunction occurred independently of body weight. In contrast, females did not exhibit changes in cardiovascular function between diets.ConclusionsThe higher prevalence of T2DM in males correlates with their susceptibility to develop subtle diastolic cardiac dysfunction when fed a Western style diet (throughout most of their lifespan) despite no systemic evidence of metabolic syndrome, let alone T2DM.

show abstract

Section: Resultsmentioning

confidence: 99%

Cardiovascular sexual dimorphism in a diet-induced type 2 diabetes rodent model, the Nile rat (Arvicanthis niloticus)

et al. 2018

View full text Add to dashboard Cite

show abstract

“…26 A study in db/db mice suggested that systemic hyperinsulinemia contributed to cardiac hypertrophy, which could be blocked by the deletion of insulin-like growth factor-1R. 27 Continuous administration of insulin for 7 weeks using osmotic pumps increased LV mass and relative wall thickness in rats. 28 In isolated rat cardiomyocytes, insulin treatment induced cardiomyocyte hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Dihydrotanshinone I Ameliorates Cardiac Hypertrophy in Diabetic Mice Induced by Chronic High-Fat Feeding

Lei

Xiao

et al. 2020

Natural Product Communications

View full text Add to dashboard Cite

Salvia miltiorrhiza Bge. (Danshen) is widely used to improve blood circulation and the dredge meridian in traditional Chinese medicine. In the present study, we evaluated the effects of dihydrotanshinone I (DHTS), a natural product from Danshen, on chronic high-fat feeding-induced cardiac remodeling and dysfunction. DHTS (25 mg/kg, intraperitoneal) did not affect blood glucose, insulin levels, and glucose intolerance. However, it alleviated diastolic dysfunction induced by the high-fat diet, as indicated by the increase in the ratio of peak early filling velocity to peak late filling velocity of the mitral and suppression of the extension of the isovolumic relaxation phase of the left ventricle. Further investigations revealed that DHTS ameliorated high-fat induced cardiac hypertrophy in mice and suppressed insulin-induced enlargement of cardiomyocytes in vitro. In neonatal cardiomyocytes, DHTS restored insulin-induced suppression of CCAAT/enhancer-binding protein beta-2 isoform (CEBPβ) and the phosphorylation of glycogen synthase kinase-3β (GSK3β) and extracellular signal-regulated kinase (ERK). Taken together, our results indicated that DHTS ameliorated cardiac hypertrophy and diastolic dysfunction in high-fat-fed mice, probably through the inhibition of insulin-induced suppression of CEBPβ and phosphorylation of GSK3β and ERK in cardiomyocytes.

show abstract

“…The GH/IGF-1 axis enhances the calcium intracellular and cardiomyocytes contractility. In obesity and type 2 diabetes mellitus (T2DM), IGF-1 can induce cardiomyocytes hypertrophy through overactivity of growth pathway [66].…”

Section: Insulin Growth Factor 1 (Igf-1)mentioning

confidence: 99%

Myocardium Metabolism in Physiological and Pathophysiological States: Implications of Epicardial Adipose Tissue and Potential Therapeutic Targets

Gandoy-Fieiras¹,

González-Juanàtey

Eiras

2020

IJMS

View full text Add to dashboard Cite

The main energy substrate of adult cardiomyocytes for their contractility are the fatty acids. Its metabolism generates high ATP levels at the expense of high oxygen consumption in the mitochondria. Under low oxygen supply, they can get energy from other substrates, mainly glucose, lactate, ketone bodies, etc., but the mitochondrial dysfunction, in pathological conditions, reduces the oxidative metabolism. In consequence, fatty acids are stored into epicardial fat and its accumulation provokes inflammation, insulin resistance, and oxidative stress, which enhance the myocardium dysfunction. Some therapies focused on improvement the fatty acids entry into mitochondria have failed to demonstrate benefits on cardiovascular disorders. Oppositely, those therapies with effects on epicardial fat volume and inflammation might improve the oxidative metabolism of myocardium and might reduce the cardiovascular disease progression. This review aims at explain (a) the energy substrate adaptation of myocardium in physiological conditions, (b) the reduction of oxidative metabolism in pathological conditions and consequences on epicardial fat accumulation and insulin resistance, and (c) the reduction of cardiovascular outcomes after regulation by some therapies.

show abstract

Activation of IGF-1 receptors and Akt signaling by systemic hyperinsulinemia contributes to cardiac hypertrophy but does not regulate cardiac autophagy in obese diabetic mice

Cited by 31 publications

References 54 publications

Cardiovascular sexual dimorphism in a diet-induced type 2 diabetes rodent model, the Nile rat (Arvicanthis niloticus)

Cardiovascular sexual dimorphism in a diet-induced type 2 diabetes rodent model, the Nile rat (Arvicanthis niloticus)

Dihydrotanshinone I Ameliorates Cardiac Hypertrophy in Diabetic Mice Induced by Chronic High-Fat Feeding

Myocardium Metabolism in Physiological and Pathophysiological States: Implications of Epicardial Adipose Tissue and Potential Therapeutic Targets

Contact Info

Product

Resources

About