GLP-1 Agonists Liraglutide Improved Vascular Endothelial Function in Type 2 Diabetes Rats

Objective: Liraglutide (LIRA), a Glucagon-like peptide-1 (GLP-1) receptor agonist, showed potential vascular protective effects with the mechanism remained incompletely understood. Therefore, this study aimed to investigate whether LIRA exerts its effect on vascular endothelial function in rats with type 2 diabetes mellitus (T2DM) via caveolin-1/ endothelial oxide synthase (eNOS) expression. Methods: T2DM rats were used as study subjects and randomly divided into four groups: 1) Veh group, 2) Veh+LIRA group, 3) T2DM group, and 4) T2DM+LIRA group. All rats received either saline or LIRA 0.2 mg/kg (by i.p. injection) per day for 4 weeks. After the model was successfully established, vascular endothelial function was determined the effect of vasodilator to mesenteric artery rings. Immunofluorescence and western blot were performed to understand the molecular mechanism. Cultured HUVECs with small interfering RNA (siRNA) under high glucose (HG), NO concentration, and western blot were performed to understand the molecular mechanism between LIRA and vascular endothelial function. Results: Based on our results, the LIRA reduced hyperglycemia and ameliorated vascular endothelial dysfunction in type 2 diabetic mice. LIRA activated eNOS phosphorylation, suppressing oxidative stress and enhancing endothelium-dependent vasorelaxation of mesenteric arteries. Besides, from its anti-oxidative capacity, LIRA activated eNOS to dilate the mesenteric arteries via the downregulation of Cav-1. Conclusion: LIRA ameliorates vascular endothelial dysfunction in rats with type 2 diabetes mellitus via anti-oxidative and activated eNOS by downregulated Cav-1.

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Renal denervation improves vascular endothelial dysfunction by inducing autophagy via AMPK/mTOR signaling activation in a rat model of type 2 diabetes mellitus with insulin resistance

Acta Diabetologica ◽

10.1007/s00592-020-01532-6 ◽

2020 ◽

Vol 57 (10) ◽

pp. 1227-1243 ◽

Cited By ~ 2

Author(s):

Yong Wang ◽

Bikash Rijal ◽

Mengping Xu ◽

Zhuqing Li ◽

Yunan An ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Endothelial Dysfunction ◽

Renal Denervation ◽

Vascular Endothelial ◽

Vascular Endothelial Dysfunction ◽

Signaling Activation

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Changes in endothelial function during educational hospitalization and the contributor to improvement of endothelial function in type 2 diabetes mellitus

Scientific Reports ◽

10.1038/s41598-020-72341-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yukiko Goshima ◽

Yosuke Okada ◽

Keiichi Torimoto ◽

Yoshihisa Fujino ◽

Yoshiya Tanaka

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Endothelial Function ◽

Multivariable Analysis ◽

Vascular Endothelial ◽

Single Factor ◽

Vascular Endothelial Function ◽

Before And After

Abstract Only a few reports have examined vascular endothelial function before and after educational hospitalization and the factors that affect it in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess vascular endothelial function before and after educational hospitalization and identify factors that affect it. In 65 patients with T2DM who underwent peripheral arterial tonometry (EndoPAT) before and after hospitalization, vascular endothelial function (reactive hyperemia index [RHI]), glucose metabolism, lipid metabolism, and blood pressure were assessed before and after hospitalization. The primary endpoint was hospitalization-induced changes in vascular endothelial function. Educational hospitalization significantly improved the natural logarithmically scaled RHI (L_RHI) from 0.555 ± 0.212 to 0.625 ± 0.245 (p = 0.012). Multivariable logistic regression analysis identified hypoglycemia during hospitalization as the single factor that significantly altered vascular endothelial function (p = 0.019). The odds of achieving normal vascular endothelial function were 0.08 times lower (95% confidence interval, 0.01–0.67) for each episode of hypoglycemia. Furthermore, multivariable analysis identified hypoglycemia during hospitalization as the single factor that worsened L_RHI. Our study showed that educational hospitalization of patients with T2DM improved vascular endothelial function, and that the development of hypoglycemic episodes had a significant negative impact on normalization of vascular endothelial function.

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