Endocrinology and Metabolism

Original Articles

Endocrine Research
Effects of Glucagon-Like Peptide-1 Analogue and Fibroblast Growth Factor 21 Combination on the Atherosclerosis-Related Process in a Type 2 Diabetes Mouse Model: Jin Hee Kim, Gha Young Lee, Hyo Jin Maeng, Hoyoun Kim, Jae Hyun Bae, Kyoung Min Kim, Soo Lim; Endocrinol Metab. 2021;36(1):157-170. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.781

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Background
Glucagon-like peptide-1 (GLP-1) analogues regulate glucose homeostasis and have anti-inflammatory properties, but cause gastrointestinal side effects. The fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism that has poor pharmacokinetic properties, including a short half-life. To overcome these limitations, we investigated the effect of a low-dose combination of a GLP-1 analogue and FGF21 on atherosclerosis-related molecular pathways.
Methods
C57BL/6J mice were fed a high-fat diet for 30 weeks followed by an atherogenic diet for 10 weeks and were divided into four groups: control (saline), liraglutide (0.3 mg/kg/day), FGF21 (5 mg/kg/day), and low-dose combination treatment with liraglutide (0.1 mg/kg/day) and FGF21 (2.5 mg/kg/day) (n=6/group) for 6 weeks. The effects of each treatment on various atherogenesisrelated pathways were assessed.
Results
Liraglutide, FGF21, and their low-dose combination significantly reduced atheromatous plaque in aorta, decreased weight, glucose, and leptin levels, and increased adiponectin levels. The combination treatment upregulated the hepatic uncoupling protein-1 (UCP1) and Akt1 mRNAs compared with controls. Matric mentalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were downregulated and phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated in liver of the liraglutide-alone and combination-treatment groups. The combination therapy also significantly decreased the proliferation of vascular smooth muscle cells. Caspase-3 was increased, whereas MMP-9, ICAM-1, p-Akt, and p-ERK1/2 were downregulated in the liraglutide-alone and combination-treatment groups.
Conclusion
Administration of a low-dose GLP-1 analogue and FGF21 combination exerts beneficial effects on critical pathways related to atherosclerosis, suggesting the synergism of the two compounds.

Citations

Citations to this article as recorded by

Current status and future perspectives of FGF21 analogues in clinical trials
Zara Siu Wa Chui, Qing Shen, Aimin Xu
Trends in Endocrinology & Metabolism.2024;[Epub] CrossRef
Design and pharmaceutical evaluation of bifunctional fusion protein of FGF21 and GLP-1 in the treatment of nonalcoholic steatohepatitis
Xianlong Ye, Yingli Chen, Jianying Qi, Shenglong Zhu, Yuanyuan Wu, Jingjing Xiong, Fei Hu, Zhimou Guo, Xinmiao Liang
European Journal of Pharmacology.2023; 952: 175811. CrossRef
Use of FGF21 analogs for the treatment of metabolic disorders: a systematic review and meta-analysis
Maria Paula Carbonetti, Fernanda Almeida-Oliveira, David Majerowicz
Archives of Endocrinology and Metabolism.2023;[Epub] CrossRef
Exploring the potential mechanism of Simiao Yongan decoction in the treatment of diabetic peripheral vascular disease based on network pharmacology and molecular docking technology
Fang Cao, Yongkang Zhang, Yuan Zong, Xia Feng, Junlin Deng, Yuzhen Wang, Yemin Cao
Medicine.2023; 102(52): e36762. CrossRef
The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria
Rewaa Ali, Tarek Khamis, Gamal Enan, Gamal El-Didamony, Basel Sitohy, Gamal Abdel-Fattah
Molecules.2022; 27(7): 2270. CrossRef
Nonalcoholic Steatohepatitis (NASH) and Atherosclerosis: Explaining Their Pathophysiology, Association and the Role of Incretin-Based Drugs
Eleftheria Galatou, Elena Mourelatou, Sophia Hatziantoniou, Ioannis S. Vizirianakis
Antioxidants.2022; 11(6): 1060. CrossRef
Unlocking the Therapeutic Potential of Glucagon-Like Peptide-1 Analogue and Fibroblast Growth Factor 21 Combination for the Pathogenesis of Atherosclerosis in Type 2 Diabetes
Jang Won Son
Endocrinology and Metabolism.2021; 36(1): 57. CrossRef
Effects of fasting on skeletal muscles and body fat of adult and old C57BL/6J mice
Mindaugas Kvedaras, Petras Minderis, Leonardo Cesanelli, Agne Cekanauskaite, Aivaras Ratkevicius
Experimental Gerontology.2021; 152: 111474. CrossRef
The Role of Fibroblast Growth Factor 21 in Diabetic Cardiovascular Complications and Related Epigenetic Mechanisms
Mengjie Xiao, Yufeng Tang, Shudong Wang, Jie Wang, Jie Wang, Yuanfang Guo, Jingjing Zhang, Junlian Gu
Frontiers in Endocrinology.2021;[Epub] CrossRef
Liraglutide Decreases Liver Fat Content and Serum Fibroblast Growth Factor 21 Levels in Newly Diagnosed Overweight Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease
Xinyue Li, Xiaojuan Wu, Yumei Jia, Jing Fu, Lin Zhang, Tao Jiang, Jia Liu, Guang Wang, Claudia Cardoso
Journal of Diabetes Research.2021; 2021: 1. CrossRef
Differential importance of endothelial and hematopoietic cell GLP-1Rs for cardiometabolic versus hepatic actions of semaglutide
Brent A. McLean, Chi Kin Wong, Kiran Deep Kaur, Randy J. Seeley, Daniel J. Drucker
JCI Insight.2021;[Epub] CrossRef

Endocrine Research
Effects of Lobeglitazone, a New Thiazolidinedione, on Osteoblastogenesis and Bone Mineral Density in Mice: Kyoung Min Kim, Hyun-Jin Jin, Seo Yeon Lee, Hyo Jin Maeng, Gha Young Lee, Tae Jung Oh, Sung Hee Choi, Hak Chul Jang, Soo Lim; Endocrinol Metab. 2017;32(3):389-395. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.389

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Background

Bone strength is impaired in patients with type 2 diabetes mellitus despite an increase in bone mineral density (BMD). Thiazolidinedione (TZD), a peroxisome proliferator activated receptor γ agonist, promotes adipogenesis, and suppresses osteoblastogenesis. Therefore, its use is associated with an increased risk of fracture. The aim of this study was to examine the in vitro and in vivo effects of lobeglitazone, a new TZD, on bone.

Methods

MC3T3E1 and C3H10T1/2 cells were cultured in osteogenic medium and exposed to lobeglitazone (0.1 or 1 µM), rosiglitazone (0.4 µM), or pioglitazone (1 µM) for 10 to 14 days. Alkaline phosphatase (ALP) activity, Alizarin red staining, and osteoblast marker gene expression were analyzed. For in vivo experiments, 6-month-old C57BL/6 mice were treated with vehicle, one of two doses of lobeglitazone, rosiglitazone, or pioglitazone. BMD was assessed using a PIXImus2 instrument at the baseline and after 12 weeks of treatment.

Results

As expected, in vitro experiments showed that ALP activity was suppressed and the mRNA expression of osteoblast marker genes RUNX2 (runt-related transcription factor 2) and osteocalcin was significantly attenuated after rosiglitazone treatment. By contrast, lobeglitazone at either dose did not inhibit these variables. Rosiglitazone-treated mice showed significantly accelerated bone loss for the whole bone and femur, but BMD did not differ significantly between the lobeglitazone-treated and vehicle-treated mice.

Conclusion

These findings suggest that lobeglitazone has no detrimental effects on osteoblast biology and might not induce side effects in the skeletal system.

Citations

Citations to this article as recorded by

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697. CrossRef
Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703. CrossRef
A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Y
Diabetes & Metabolism Journal.2022; 46(6): 855. CrossRef
Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
Diabetes Therapy.2021; 12(1): 171. CrossRef
Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
Diabetes & Metabolism Journal.2021; 45(3): 326. CrossRef
Effect of lobeglitazone on motor function in rat model of Parkinson’s disease with diabetes co-morbidity
Kambiz Hassanzadeh, Arman Rahimmi, Mohammad Raman Moloudi, Rita Maccarone, Massimo Corbo, Esmael Izadpanah, Marco Feligioni
Brain Research Bulletin.2021; 173: 184. CrossRef
Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus
Jeonghoon Ha, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Seung Hyun Ko, Moo Il Kang, Sung Dae Moon, Ki-Hyun Baek
Endocrinology and Metabolism.2021; 36(4): 895. CrossRef
Xenogeneic native decellularized matrix carrying PPARγ activator RSG regulating macrophage polarization to promote ligament-to-bone regeneration
Xue Han, Lijun Liao, Tian Zhu, Yuchan Xu, Fei Bi, Li Xie, Hui Li, Fangjun Huo, Weidong Tian, Weihua Guo
Materials Science and Engineering: C.2020; 116: 111224. CrossRef
Diabetes pharmacotherapy and effects on the musculoskeletal system
Evangelia Kalaitzoglou, John L. Fowlkes, Iuliana Popescu, Kathryn M. Thrailkill
Diabetes/Metabolism Research and Reviews.2019;[Epub] CrossRef
The effects of diabetes therapy on bone: A clinical perspective
Karim G. Kheniser, Carmen M. Polanco Santos, Sangeeta R. Kashyap
Journal of Diabetes and its Complications.2018; 32(7): 713. CrossRef

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