Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats

Yamada, Shohei; Tanabe, Jun; Ogura, Yuji; Nagai, Yoshio; Sugaya, Takeshi; Ohata, Keiichi; Natsuki, Yasunori; Ichikawa, Daisuke; Watanabe, Sumi; Inoue, Kenji; Hoshino, Seiko; Kimura, Kenjiro; Shibagaki, Yugo; Kamijo‐Ikemori, Atsuko

doi:10.1007/s10157-020-02007-2

Cited by 25 publications

(32 citation statements)

References 23 publications

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“…Additionally, GLP-1 agonists have been reported to have therapeutic effects on diabetic kidney disease ( Yamada et al, 2021 ) through promotion of autophagy.…”

Section: Autophagy Enhancer In Metabolic Disordersmentioning

confidence: 99%

Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases

Park

Lee

2022

Front. Cell Dev. Biol.

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Autophagy is pivotal in the maintenance of organelle function and intracellular nutrient balance. Besides the role of autophagy in the homeostasis and physiology of the individual tissues and whole organism in vivo, dysregulated autophagy has been incriminated in the pathogenesis of a variety of diseases including metabolic diseases, neurodegenerative diseases, cardiovascular diseases, inflammatory or immunological disorders, cancer and aging. Search for autophagy modulators has been widely conducted to amend dysregulation of autophagy or pharmacologically modulate autophagy in those diseases. Current data support the view that autophagy modulation could be a new modality for treatment of metabolic syndrome associated with lipid overload, human-type diabetes characterized by deposition of islet amyloid or other diseases including neurodegenerative diseases, infection and cardiovascular diseases. While clinically available bona fide autophagy modulators have not been developed yet, it is expected that on-going investigation will lead to the development of authentic autophagy modulators that can be safely administered to patients in the near future and will open a new horizon for treatment of incurable or difficult diseases.

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“…Additionally, GLP-1 agonists have been reported to have therapeutic effects on diabetic kidney disease ( Yamada et al, 2021 ) through promotion of autophagy.…”

Section: Autophagy Enhancer In Metabolic Disordersmentioning

confidence: 99%

Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases

Park

Lee

2022

Front. Cell Dev. Biol.

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“…Therefore, serum cystatin C was used for evaluation of renal function in the present study. The levels of serum cystatin C and insulin, urinary rat L-FABP, and rat albumin were measured using the same commercially available kits as those described in our previous study [19]. The serum total cholesterol and triglyceride levels were measured in the SRL clinical laboratory testing services (Tokyo, Japan) [19].…”

Section: Animalsmentioning

confidence: 99%

“…The levels of serum cystatin C and insulin, urinary rat L-FABP, and rat albumin were measured using the same commercially available kits as those described in our previous study [19]. The serum total cholesterol and triglyceride levels were measured in the SRL clinical laboratory testing services (Tokyo, Japan) [19]. Serum interleukin-6 (IL-6) and brainderived neurotrophic factor (BDNF) were measured using each ELISA kit from R&D Systems (Minneapolis, MN, USA).…”

Section: Animalsmentioning

confidence: 99%

“…The midsection of each excised kidney was dissected in the minor axial direction. Both pieces were fixed in 10% buffered formalin or methyl Carnoy's solution (60% methanol, 30% chloroform, and 10% glacial acetic acid) and embedded in paraffin [19]. Serial sections (3 μm thick) were prepared for renal histological assessment, including periodic acid-Schiff (PAS) staining and immunohistochemistry.…”

Section: Renal Histological and Morphometric Analysesmentioning

confidence: 99%

“…Spontaneously diabetic Torii (SDT) fatty (SDT.Cg-Lepr fa /JttJcl) rats mimic the human pathophysiology of type 2 diabetes with obesity, hypertension, and hyperlipidemia [17]. In our previous study, SDT fatty rats showed symptoms of DKD and muscle weakness at 16 weeks of age [18,19]. Therefore, the aim of this study was to investigate the beneficial effects of endurance exercise training on the kidneys and muscle by using SDT fatty rats.…”

Section: Introductionmentioning

confidence: 99%

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Endurance Exercise Training-Attenuated Diabetic Kidney Disease with Muscle Weakness in Spontaneously Diabetic Torii Fatty Rats

Kotake

Yamada

Ogura

et al. 2021

Kidney Blood Press Res

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Background The aim of this study was to evaluate protective effects of endurance exercise training against diabetic kidney disease (DKD) with muscle weakness by using male spontaneously diabetic Torii (SDT) fatty rats as type 2 diabetic animal models with obesity, hypertension, and hyperlipidemia. Methods Eight-week-old SDT fatty rats (n = 12) and Sprague–Dawley (SD) rats (n = 10) were randomly divided into exercise (Ex; SDT-Ex: n = 6, SD-Ex: n = 5) and sedentary groups (SDT-Cont: n = 6, SD-Cont: n = 5), respectively. Each group underwent regular treadmill exercise four times a week from ages 8 to 16 weeks. Results The exercise attenuated hypertension and hyperlipidemia and prevented increases in renal parameter levels without affecting blood glucose levels. In the SDT fatty rats, it prevented induction of renal morphological abnormalities in the interstitium of the superficial and intermediate layers of the cortex. Downregulated expression of endothelial nitric oxide synthase in the glomerulus of the SDT fatty rats was significantly upregulated by the exercise. The exercise upregulated the renal expressions of both medium-chain acyl-CoA dehydrogenase and peroxisome proliferator-activated receptor γ coactivator-1α related to fatty acid metabolism. It increased muscle strength and both muscle weight and cross-sectional area of type IIb muscle fibers in the extensor digitorum longus muscle in the SDT fatty rats. Conclusion Endurance exercise training in type 2 diabetes ameliorates DKD by improving endothelial abnormality and enhancing fatty acid metabolism in addition to attenuated hypertension, hyperlipidemia, and muscle weakness independently of blood glucose levels.

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