Uncovering the potential molecular mechanism of liraglutide to alleviate the effects of high glucose on myoblasts based on high-throughput transcriptome sequencing technique.

BACKGROUND: Myoblasts play an important role in muscle growth and repair, but the high glucose environment severely affects their function. The purpose of this study is to explore the potential molecular mechanism of liraglutide in alleviating the effects of high glucose environments on myoblasts. METHODS: MTT, western blot, and ELISA methods were used to investigate the role of liraglutide on C2C12 myoblasts induced by high glucose. The high-throughput transcriptome sequencing technique was used to sequence C2C12 myoblasts from different treated groups. The DESeq2 package was used to identify differentially expressed-mRNAs (DE-mRNAs). Then, functional annotations and alternative splicing (AS) were performed. The Cytoscape-CytoHubba plug-in was used to identify multicentric DE-mRNAs. RESULTS: The MTT assay results showed that liraglutide can alleviate the decrease of myoblasts viability caused by high glucose. Western blot and ELISA tests showed that liraglutide can promote the expression of AMPKα and inhibit the expression of MAFbx, MuRF1 and 3-MH in myoblasts. A total of 15 multicentric DE-mRNAs were identified based on the Cytoscape-CytoHubba plug-in. Among them, Top2a had A3SS type AS. Functional annotation identifies multiple signaling pathways such as metabolic pathways, cytokine-cytokine receptor interaction, cAMP signaling pathway and cell cycle. CONCLUSION: Liraglutide can alleviate the decrease of cell viability and degradation of muscle protein caused by high glucose, and improves cell metabolism and mitochondrial activity. The molecular mechanism of liraglutide to alleviate the effect of high glucose on myoblasts is complex. This study provides a theoretical basis for the clinical effectiveness of liraglutide in the treatment of skeletal muscle lesions in diabetes.

Association of Different Obesity Phenotypes with Sarcopenia in Han Chinese Middle-Aged and Elderly with Type 2 Diabetes Individuals.

Purpose: To investigate the relationship between different obesity phenotypes and sarcopenia in hospitalized Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional study included 385 men. Anthropometric measurements including applied the determination method of Dual-energy X-ray absorptiometry (DXA) determination of limb skeletal muscle mass index (ASMI) and blood samples were analyzed. The people were divided into four groups according to body mass index (BMI) (≥24kg/m2) and waist circumference (WC) (female ≥85cm, male ≥90cm). Group A (BMI and WC were normal), Group B (BMI was normal and high WC), Group C (high BMI and WC were normal), and Group D (BMI and WC were abnormal). Results: The prevalence rates of sarcopenia and abdominal obesity were 32.2% and 74.0%, respectively. The detection rate of lower ASMI decreased gradually from Group A to Group D(74.6% vs 68.3% vs 54.5% vs 51.6%, χ 2 =14.243, P=0.003). Logistic analysis showed that the risk of lower ASMI were decreased by 62.4% (95% CI: 0.149-0.950, P = 0.039) in Group C and 68.8% (95% CI: 0.165-0.593, P = 0.000) in Group D compared with Group A, respectively. The risk of lower ASMI were increased 4.153-fold (95% CI: 2.623-6.576, P = 0.000) in male. Male (OR = 4.065, 95% CI: 2.246-7.356, P = 0.000) and WC (OR = 1.053, 95% CI: 1.004-1.104, P = 0.033) were risk factors for lower ASMI, but the risk of lower ASMI was decreased by 32% (95% CI: 0.5744-0.804, P = 0.000) by elevated BMI in the overweight and obese group (Group C and Group D). Conclusion: The prevalence of sarcopenia and abdominal obesity was elevated in han Chinese middle-aged and elderly patients with T2DM. Being overweight or obesity as defined by BMI protect against sarcopenia, while abdominal obesity increases the risk of sarcopenia.

Alternative skeletal muscle index for sarcopenia diagnosis in elderly patients with type 2 diabetes mellitus: A pilot study.

Purpose: To determine an alternative skeletal muscle index (a-SMI), easy diagnosis of sarcopenia in elderly patients with type 2 diabetes mellitus (T2DM). Patients and methods: This cross-sectional study included 223 inpatients with T2DM (100 males, age range 60-89; 123 females, age range 60-87). Screening for grip strength and gait speed, measuring SMI by dual-energy X-ray absorptiometry (d-SMI) for sarcopenia diagnosis, according to the Asian Working Group for Sarcopenia (AWGS) 2019 consensus. The a-SMI was established by binary logistic regression analysis with positive screening population. To assess the conformance of the new diagnostic approach with the AWGS 2019. Results: Sarcopenia was present in 36.3% of the study population. 59 had normal d-SMI and 81 had low d-SMI in screening patients with probable sarcopenia. In univariate analyses for all positive screening population, body mass index (BMI), 25-hydroxyvitamin D (25 - (OH) VitD), high density lipoprotein cholesterol (HDL-C), hypertension (HTN), and gender were correlates of d-SMI. Binary logistic regression analysis revealed that male (B = 2.463, 95%CI: 3.640 ~ 37.883, p = 0.000), HTN (B = 1.404, 95%CI: 1.599 ~ 10.371, p = 0.003), BMI (B = -0.344, 95%CI: 0.598 ~ 0.839, p = 0.000), 25-(OH) VitD (B = -0.058, 95%CI: 0.907 ~ 0.982, p = 0.004) were independent factors for d-SMI detection. Based on the extracted four correlates, the a-SMI was determined. The area under receiver operating characteristic (ROC) curve was 0.842, sensitivity and specificity for the new diagnostic approach were 84.0% and 84.5%. In a statistical measure of agreement between the AWGS 2019 and the new diagnostic approach, the kappa coefficient was 0.669 (p < 0.001). Conclusion: The a-SMI - based on gender, obesity status, 25-(OH) VitD, and HTN history - can be used in the absence of the d-SMI to supplement the algorithm for sarcopenia diagnosis in elderly patients with T2DM.