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Dexmedetomidine restores autophagy and cardiac dysfunction in rats with streptozotocin-induced diabetes mellitus

 Ju Eun Oh  ;  Ji Hae Jun  ;  Hye Jeong Hwang  ;  Eun Jung Shin  ;  Young Jun Oh  ;  Yong Seon Choi 
 ACTA DIABETOLOGICA, Vol.56(1) : 105-114, 2019 
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Autophagy ; Cardiac function ; Dexmedetomidine ; Diabetic cardiomyopathy ; Type 1 diabetes
AIMS: Dexmedetomidine (DEX), a highly selective and potent α2-adrenergic receptor agonist, has anti-apoptotic, anti-inflammatory, and anti-oxidative stress effects in diabetes mellitus (DM) rats. The underlying molecular mechanisms and signaling pathways of diabetic cardiomyopathy remain poorly understood. This study aimed to elucidate the effect of DEX on cardiac function in DM rats.

METHODS: Eight-week-old male Sprague Dawley rats were divided into three groups: control (n = 5), diabetes (DM, n = 7), and diabetes + DEX (DM + DEX, n = 10). DM was induced via intraperitoneal injection of streptozotocin (70 mg/kg); at 3 days later, DEX (1 µg/kg/h) was administered for 4 weeks. Cardiac function was evaluated using pressure-volume loop analysis and echocardiography. Left ventricular (LV) histological sections were used to analyze the interstitial collagen fraction. Using the LV samples, we performed a western blot analysis to evaluate signaling pathways and autophagic markers.

RESULTS: The DM group had lower body weight and higher blood glucose level and heart weight/body weight ratio than the control group. However, metabolic changes did not differ between the DM and DM + DEX groups. Pressure-volume loop analysis and echocardiography showed impaired cardiac function, evidenced by a decrease in systolic and diastolic function, in both DM groups. DEX treatment in DM rats was associated with increased LV end-systolic pressure, LV contractility, cardiac output, and relaxed LV function compared with that in non-treated DM rats. LC3B and autophagy-related gene (ATG) proteins increased in the hearts of DM rats compared with the hearts of control rats. However, DEX reduced the expression of LC3B and ATG proteins in the hearts of DM rats. Increased p-ERK and decreased p-AKT were reduced in the hearts of DEX-treated DM rats.

CONCLUSIONS: DEX reduces cardiac dysfunction and impaired autophagy in DM rats. This study reinforces our understanding of the potential anti-autophagic effect of DEX in patients with diabetic cardiomyopathy.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Oh, Young Jun(오영준) ORCID logo https://orcid.org/0000-0002-6258-5695
Choi, Yong Seon(최용선) ORCID logo https://orcid.org/0000-0002-5348-864X
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