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
| Autor: | Soo Lim, Jae Hyun Bae, Hyo Jin Maeng, Kyoung Min Kim, Gha Young Lee, Jin Hee Kim, Hoyoun Kim |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
FGF21 Combination therapy Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Carbohydrate metabolism Fibroblast growth factor 21 lcsh:Diseases of the endocrine glands. Clinical endocrinology Mice 03 medical and health sciences 0302 clinical medicine Endocrinology Diabetes mellitus Glucagon-Like Peptide 1 Internal medicine medicine Animals Glucose homeostasis Humans Inflammation lcsh:RC648-665 Adiponectin Chemistry Liraglutide Leptin Atherosclerosis Glucagon-like peptide-1 Mice Inbred C57BL Fibroblast Growth Factors Editorial Diabetes Mellitus Type 2 030220 oncology & carcinogenesis Original Article medicine.drug |
| Zdroj: | Endocrinology and Metabolism Endocrinology and Metabolism, Vol 36, Iss 1, Pp 157-170 (2021) |
| ISSN: | 2093-5978 2093-596X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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