Downregulation of oxytocin and natriuretic peptides in diabetes: possible implications in cardiomyopathy

Gutkowska, Jolanta; Broderick, Tom L.; Bogdan, Danalache; Wang, Donghao; Lavoie, Jean‐Marc; Jankowski, Marek

doi:10.1113/jphysiol.2009.176461

Cited by 47 publications

(54 citation statements)

References 52 publications

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“…The contribution of this system to the development of diabetic cardiomyopathy is indicated by the fact that chronic administration of OT and BNP prevented cardiac dysfunction and heart remodeling naturally developing in the db/db mice 30,31. We have demonstrated that ET improves expression of the OT–NP system in ovariectomized rats32 but fails to reverse most components of this cardioprotective system in the diabetic mouse 28,33. It is unknown to what extent the development of cardiomyopathy in exercised db/db mice is associated with binge eating that is common in the diabetic db/db mouse 34.…”

Section: Introductionmentioning

confidence: 77%

“…In heart, OT exerts direct cardioprotection through the OT receptor (OTR), or indirectly via the stimulation of natriuretic peptides (NPs; atrial NP [ANP], brain NP [BNP], and C-type) and nitric oxide (NO) synthesis 26,27. This functional OT–NP–NO system is downregulated in hearts from db/db mice 28,29. The contribution of this system to the development of diabetic cardiomyopathy is indicated by the fact that chronic administration of OT and BNP prevented cardiac dysfunction and heart remodeling naturally developing in the db/db mice 30,31.…”

Section: Introductionmentioning

confidence: 99%

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The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Jankowski

Gutkowska

2017

DMSO

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BackgroundRegular exercise training (ET) and caloric restriction (CR) are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT)–natriuretic peptide (NP) system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity.MethodsFive-week-old male db/db mice were assigned to the following groups: sedentary, ET, and ET + CR. Nonobese heterozygote littermates served as controls. ET was performed on a treadmill at moderate intensity, and CR was induced by reducing food intake by 30% of that consumed by sedentary db/db mice for a period of 8 weeks.ResultsAfter 8 weeks, only ET + CR, but not ET, slightly improved body weight compared to sedentary db/db mice. Regardless of the treatment, db/db mice remained hyperglycemic. Hearts from db/db mice demonstrated reduced expression of genes linked to the cardiac OT–NP system. In fact, compared to control mice, mRNA expression of GATA binding protein 4 (GATA4), OT receptor, OT, brain NP, NP receptor type C, and endothelial nitric oxide synthase (eNOS) was decreased in hearts from sedentary db/db mice. Both ET alone and ET + CR increased the mRNA expression of GATA4 compared to sedentary db/db mice. Only ET combined with CR produced increased eNOS mRNA and protein expression.ConclusionOur data indicate that enhancement of eNOS by combined ET and CR may improve coronary endothelial vasodilator dysfunction in type 2 diabetes but did not prevent the downregulation of cardiac expression in the OT–NP system, possibly resulting from the sustained hyperglycemia and obesity in diabetic mice.

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Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Jankowski

Gutkowska

2017

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“…In such affection, fibrosis affects several organs including kidney, liver, heart or the adipose tissue, and its intensity is negatively correlated with the degree of insulin-sensitivity [108][109][110][111][112]. Our group has shown an overproduction of LPA in kidney and adipose tissue from insulin-resistant obese individuals resulting from an over-expression of the LPA-producing enzyme autotaxin [113,114].…”

Section: Expert Opinion and Conclusionmentioning

confidence: 86%

Lysophosphatidic acid-1-receptor targeting agents for fibrosis

Rancoule

Pradère

Gonzalez

et al. 2011

Expert Opinion on Investigational Drugs

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“…Regular exercise can prevent the progression of diabetes-related complications and improve overall cardiovascular health. Based on the results of exercise-based studies glucose control is not achieved in the obese diabetic db/db mouse [25,26,[51][52][53][54]. This should not raise any doubts regarding the suitably of this model for training studies, because benefits on other cardiovascular risk factors have been reported.…”

Section: Discussionmentioning

confidence: 99%

Role of Corticosterone and Expression of 11ß-Hydroxysteroid Dehydrogenase Type 1 in Liver on Post-Exercise Hyperglycemia in the Obese Diabetic Mouse

Broderick

2017

Adv Tech Biol Med

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Exercise training is recommended for the treatment of diabetes mellitus for the benefits on blood glucose control, obesity, and cardiometabolic risk factors. Exercise decreases adipose tissue content and fasting blood glucose, and improves insulin sensitivity. The diet-induced or spontaneous insulin-resistant obese and diabetic rat models to study the effects of exercise training have been widely used because of the favorable outcome on glucose homeostasis. However, the effects of exercise on overall glucose control in the db/db mouse of diabetes remain unclear. The db/db mouse resembles the human condition of type 2 diabetes mellitus and is characterized by hyperleptinemia, hyperglycemia and obesity resulting from a mutation in the leptin receptor gene. The db/db mouse exhibits hypercorticosteronemia, which is also reflective of the human condition. Depending on the exercise training regimen, glucose metabolism is either slightly improved or is further compromised. In this communication, the effects of voluntary and forced treadmill exercise running on glucose control in the db/db mouse are mentioned. In addition, the effects of acute exercise on glucose homeostasis are discussed, along with potential mechanisms explaining the post-exercise hyperglycemia seen in the db/db mouse. to elicit a greater stimulus based on intensity and training volume (3-fold higher than voluntary running), and with expectations that this would decrease both the obesity and hyperglycemia in db/db mice. After 12 weeks of voluntary wheel running, body weight dropped by ~5% while fasting blood glucose levels decreased by ~21% compared to sedentary db/db mice (Figures 1 and 2). Forced treadmill running however, did not overcome the disturbances associated with the db/db mouse. In fact, both body weight and blood glucose were increased by ~8-10% and mice remained insulin resistant (Figure 3). When the data was expressed as percent change from the onset of exercise training, the greatest changes in body weight and fasting blood glucose levels were observed in db/db mice subjected to treadmill running (Table 1). Based on these observations, increasing the training volume by altering intensity does not always correlate with greater weight loss and improved metabolic control in the db/db mouse. Results from earlier studies in obesity models have suggested that an exaggerated stress response associated with forced treadmill exercise could explain these unfavorable changes in the db/db mouse. Daily short-term exposure to stress can induce adrenal gland hypertrophy and disruption the consequences of exercise training on cardiovascular and metabolic outcome in the diabetic state [11][12][13][14][15]. For these reasons, the use of these particular models is justified in exercise studies and for translationalbased application in the treatment of humans with this metabolic disorder. However, in recent years, the use of the db/db mouse model of diabetes to investigate the impact of exercise training has gained popularity. Yet, since the early...

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Downregulation of oxytocin and natriuretic peptides in diabetes: possible implications in cardiomyopathy

Cited by 47 publications

References 52 publications

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse

Lysophosphatidic acid-1-receptor targeting agents for fibrosis

Role of Corticosterone and Expression of 11ß-Hydroxysteroid Dehydrogenase Type 1 in Liver on Post-Exercise Hyperglycemia in the Obese Diabetic Mouse

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