scholarly journals MicroRNA-193b impairs muscle growth in mouse models of type 2 diabetes by targeting the PDK1/Akt signalling pathway

Diabetologia ◽  
2021 ◽  
Author(s):  
Shu Yang ◽  
Guangyan Yang ◽  
Han Wu ◽  
Lin Kang ◽  
Jiaqing Xiang ◽  
...  

Abstract Aims/hypothesis Type 2 diabetes is associated with a reduction in skeletal muscle mass; however, how the progression of sarcopenia is induced and regulated remains largely unknown. We aimed to find out whether a specific microRNA (miR) may contribute to skeletal muscle atrophy in type 2 diabetes. Methods Adeno-associated virus (AAV)-mediated skeletal muscle miR-193b overexpression in C57BLKS/J mice, and skeletal muscle miR-193b deficiency in db/db mice were used to explore the function of miR-193b in muscle loss. In C57BL/6 J mice, tibialis anterior-specific deletion of 3-phosphoinositide-dependent protein kinase-1 (PDK1), mediated by in situ AAV injection, was used to confirm whether miR-193b regulates muscle growth through PDK1. Serum miR-193b levels were also analysed in healthy individuals (n = 20) and those with type 2 diabetes (n = 20), and correlations of miR-193b levels with HbA1c, fasting blood glucose (FBG), body composition, triacylglycerols and C-peptide were assessed. Results In this study, we found that serum miR-193b levels increased in individuals with type 2 diabetes and negatively correlated with muscle mass in these participants. Functional studies further showed that AAV-mediated overexpression of miR-193b induced muscle loss and dysfunction in healthy mice. In contrast, suppression of miR-193b attenuated muscle loss and dysfunction in db/db mice. Mechanistic analysis revealed that miR-193b could target Pdk1 expression to inactivate the Akt/mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway, thereby inhibiting protein synthesis. Therefore, knockdown of PDK1 in healthy mice blocked miR-193b-induced inactivation of the Akt/mTOR/S6K pathway and impairment of muscle growth. Conclusions/interpretation Our results identified a previously unrecognised role of miR-193b in muscle function and mass that could be a potential therapeutic target for treating sarcopenia. Graphical abstract

2018 ◽  
Author(s):  
Se-Hwa Kim ◽  
Soo-Kyung Kim ◽  
Young-Ju Choi ◽  
Seok-Won Park ◽  
Eun-Jig Lee ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 771-P
Author(s):  
SODAI KUBOTA ◽  
HITOSHI KUWATA ◽  
SAKI OKAMOTO ◽  
DAISUKE YABE ◽  
KENTA MUROTANI ◽  
...  

2014 ◽  
Vol 61 (3) ◽  
pp. 281-287 ◽  
Author(s):  
Kanako Shishikura ◽  
Keiji Tanimoto ◽  
Satoshi Sakai ◽  
Yoshimi Tanimoto ◽  
Jungo Terasaki ◽  
...  

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tatiana de Paula ◽  
Mauren de Freitas ◽  
Vanessa Lopes ◽  
Maria Elisa Miller ◽  
Karen Araujo ◽  
...  

Abstract Objectives The aim of the study was to establish the prevalence of sarcopenia and associated factors in elderly with type 2 diabetes (DM) in southern Brazil. Methods A cross-sectional study was performed in 240 patients with type 2 DM. The diagnosis of sarcopenia was performed according to EWGSOP criteria. Muscle mass was calculated by skeletal muscle mass index (appendicular skeletal muscle mass/height² - Inbody® bioimpendance). Muscle strength was assessed by manual grip strength (Jamar® dynamometer) and physical performance was assessed by the sit and lift test. Patients with type 2 DM with age ≥60 years and with the ability to ambulate were selected. Patients with recent cardiovascular events, serum creatinine >2.0 mg/dl, use of corticosteroids and BMI >40 kg/m² were excluded. The sample size was 240 patients based on meta-analysis who found 17% sarcopenia in elderly patients without DM. Results We included 240 patients aged 68.4 ± 5.5 years, 53.2% were women and the duration of DM was 15 (8–22) years, the BMI was 29.4 ± 4.4 kg/m². The prevalence of sarcopenia was 21% and men had more sarcopenia (75%). Patients with sarcopenia walk less [3541 (2227–4574) vs. 4521 (3037–5678) steps, P = 0.013], drink more alcohol [21 (56.8%) vs. 71 (31.8%); P < 0.034] and have lower total cholesterol levels [146 ± 41 Vs. 168 ± 43; P = 0.007] than the group without sarcopenia. In multivariate logistic regression models, walking < 3760 steps [OR = 2868; CI 95% 1.331–6.181] and male [OR = 5285; CI 95% 2261–12,350], were associated with sarcopenia. Conclusions The prevalence of sarcopenia was 21%, higher than in patients without diabetes (17%). In this group of patients, lower physical activity, and male sex were associated with sarcopenia. Funding Sources FIPE n. 160467; CAPES.


2020 ◽  
Vol 8 (1) ◽  
pp. e001027 ◽  
Author(s):  
Tomonori Kimura ◽  
Takuro Okamura ◽  
Keiko Iwai ◽  
Yoshitaka Hashimoto ◽  
Takafumi Senmaru ◽  
...  

ObjectiveReduction of muscle mass and strength is an important treatment target for patients with type 2 diabetes. Recent studies have reported that high-intensity resistance training improves physical function; however, all patients found it difficult to perform high-intensity resistance training. Radio calisthenics, considered as therapeutic exercises to promote health in Japan, are simple exercises that can be performed regardless of age and help move the muscles and joints of the whole body effectively according to the rhythm of radio. We investigated the efficacy of radio calisthenics for muscle mass in patients with type 2 diabetes in this retrospective cohort study.Research design and methodsA total of 42 hospitalized patients with type 2 diabetes were recruited. The skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass (kg) divided by height squared (m2). We defined the change of SMI as the difference of SMI between the beginning and end of hospitalization.ResultsAmong 42 patients, 15 (11 men and 4 women) performed radio calisthenics. Body weights of both radio calisthenics exercisers and non-exercisers decreased during hospitalization. The change of SMI was significantly lesser in radio calisthenics exercisers than in non-exercisers (7.1±1.4 to 7.1±1.3, –0.01±0.09 vs 6.8±1.1 to 6.5±1.2, –0.27±0.06 kg/m2, p=0.016). The proportion of decreased SMI was 85.2% (23/27 patients) in non-radio calisthenics exercisers, whereas that in radio calisthenics exercisers was 46.7% (7/15 patients).ConclusionsRadio calisthenics prevent the reduction of skeletal muscle mass. Thus, radio calisthenics can be considered effective for patients with type 2 diabetes.


2019 ◽  
Vol 34 (3) ◽  
pp. 209-217
Author(s):  
Ryo Shimizu ◽  
Yusuke Tando ◽  
Asami Yokoyama ◽  
Miyuki Yanagimachi

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Serena Low ◽  
Tze Pin Ng ◽  
Chin Leong Lim ◽  
Angela Moh ◽  
Su Fen Ang ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3220 ◽  
Author(s):  
Yoshitaka Hashimoto ◽  
Ayumi Kaji ◽  
Ryosuke Sakai ◽  
Fuyuko Takahashi ◽  
Rena Kawano ◽  
...  

Exercise has been reported to be effective in maintaining and recovering muscle; however, the effect of exercise combined with adequate or inadequate protein intake on muscle mass is not clear. Therefore, this study investigates the effect of exercise habit on changes in muscle mass, with adequate or inadequate protein intake. This retrospective cohort study included 214 elderly patients with type 2 diabetes. The rate of skeletal muscle mass index (SMI) change (%) was defined as ((SMI at follow-up minus SMI at baseline)/(follow-up years [kg/m2/year] × SMI at baseline [kg/m2])) × 100. Adequate protein intake was defined as protein intake ≥1.2 g/kg ideal body weight/day. During a mean follow-up duration of 18.0 (7.1) months, the rate of SMI change was −1.14 (4.10)% in the whole sample. The rate of SMI change of non-habitual exercisers with inadequate protein intake, habitual exercisers with inadequate protein intake, non-habitual exercisers with adequate protein intake, and habitual exercisers with adequate protein intake was −1.22 (3.71), −2.31 (3.30), −1.88 (4.62), and 0.36 (4.29)%, respectively. Compared with patients with exercise habit and adequate protein intake, the odds ratio for decreasing SMI was 2.50 (0.90–6.90, p = 0.078) in patients with no exercise habit and inadequate protein intake, 3.58 (1.24–10.4, p = 0.019) in those with exercise habit and inadequate protein intake, and 3.03 (1.27–7.22, p = 0.012) in those with no exercise habit and adequate protein intake, after adjusting for covariates. Therefore, exercise habit without adequate protein intake was associated with an increased risk of decreasing SMI compared with exercise habit with adequate protein intake.


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