MicroRNA regulation related to glucagon-like peptide-1 receptor agonists in controlling heart problems, high blood sugar, and obesity in type 2 diabetes
GLP-1 receptor agonists (GLP-1RAs) modify the expression of miRNAs associated with endothelial function, sugar metabolism, and adipogenesis in type 2 diabetes mellitus (T2DM).
Baseline levels of miR-15a-5p may predict weight loss in T2DM patients.
Higher levels of miR-378-3p and miR-126-3p are associated with improved glycemic control and lower HbA1c and fasting plasma glucose one year post-treatment.
Liraglutide downregulates miR-139-5p, providing protection against pancreatic β-cell apoptosis.
The expression of miR-375 in pancreatic islets may serve as a biomarker for assessing the cytoprotective effects of GLP-1RAs.
Long-acting exenatide requires miR-29b-3p for its protective effects against diabetic cardiomyopathy.
GLP-1RAs influence the regulation of exosomal miRNAs, such as miR-192, which are implicated in fibrosis and inflammation related to T2DM complications.
Simplified
BACKGROUND AND AIMS: Type 2 diabetes mellitus (T2DM) is usually complicated by cardiovascular diseases, hyperglycemia, and obesity, which worsen the outcome for the patient. Since recent evidence underlines the epigenetic role of (GLP-1RAs) in the management of these comorbidities, this study compared the effects of these agents, namely liraglutide, semaglutide, dulaglutide, and exenatide, on regulation in the management of T2DM.
RESULTS: GLP-1RAs modify the expression of miRNAs involved in endothelial function, sugar metabolism, and adipogenesis, including but not limited to miR-27b, miR-130a, and miR-210. Baseline miR-15a-5p predict weight loss, while higher miR-378-3p and miR-126-3p levels are related to better glycemic control and lower HbA1c and FPG at one year post-treatment. miR-375-5p was also reported as a predictor of HbA1c levels. Liraglutide has a protecting effect against pancreatic β-cell apoptosis by downregulating miR-139-5p. The highly-expressed miR-375 in pancreatic islets can be considered as a biomarker for assessing the cytoprotective action of GLP-1RAs on β-cells. GLP-1RAs also enhance β-cell responsiveness by promoting GLP-1 receptor expression through the suppression of miR-204. While semaglutide, semaglutide, and dulaglutide reduce both systolic and diastolic blood pressures, lixisenatide and exenatide QW did not reveal such an effect. The long-acting exenatide-induced miR-29b-3p is required for the protection against diabetic cardiomyopathy. Liraglutide modulates critical regulators of endothelial cell function and atherosclerosis, including miR-93-5p, miR-26a-5p, and miR-181a-5p. Eventually, GLP-1RAs regulation of exosomal miRNAs, such as miR-192, implicated in the development of fibrosis and inflammation in T2DM micro-cardiovascular outcomes like DKD and DR.
CONCLUSION: Additional studies will be needed in the elucidation of the relations between GLP-1RA-induced miRNAs and clinical-laboratory findings concerning the diverse populations, gender, and presence of other comorbid states in treated patients with T2DM.
Key numbers
2.9 kg
Weight Loss from
Average weight loss in T2DM patients treated with compared to placebo.
1%
HbA1c Reduction
Average reduction in HbA1c levels in T2DM patients treated with .
40-50%
40-50% Progression Risk
Chance of glucose tolerance impairment progressing to T2DM even after significant weight loss.
Full Text
We can’t show the full text here under this license.
