Genetic deletion of miR-204 improves glycemic control despite obesity in db/db mice
| Autor: | Ravinder Reddy Gaddam, Kaikobad Irani, Quixia Li, Young-Rae Kim, Mohanad Gabani, Ajit Vikram, Yumi Imai, Julia S. Jacobs, Joseph A. Promes, Akansha Mishra |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine medicine.medical_specialty medicine.medical_treatment Biophysics Glycemic Control CHOP Diet High-Fat Biochemistry Article Diabetes Mellitus Experimental 03 medical and health sciences 0302 clinical medicine Insulin-Secreting Cells Diabetes mellitus Internal medicine Animals Insulin Medicine Obesity Molecular Biology Cell Proliferation Glycemic Mice Knockout geography geography.geographical_feature_category business.industry Pancreatic islets Cell Biology Endoplasmic Reticulum Stress medicine.disease Islet Mice Mutant Strains MicroRNAs 030104 developmental biology Endocrinology medicine.anatomical_structure Hyperglycemia 030220 oncology & carcinogenesis Unfolded protein response Homeostatic model assessment Female business |
| Zdroj: | Biochem Biophys Res Commun |
| ISSN: | 0006-291X |
| Popis: | MicroRNAs (miRs) are small non-coding RNAs that regulate the target gene expression. A change in miR profile in the pancreatic islets during diabetes is known, and multiple studies have demonstrated that miRs influence the pancreatic β-cell function. The miR-204 is highly expressed in the β-cells and reported to regulate insulin synthesis. Here we investigated whether the absence of miR-204 rescues the impaired glycemic control and obesity in the genetically diabetic (db/db) mice. We found that the db/db mice overexpressed miR-204 in the islets. The db/db mice lacking miR-204 (db/db-204−/−) initially develops hyperglycemia and obesity like the control (db/db) mice but later displayed a gradual improvement in glycemic control despite remaining obese. The db/db-204−/− mice had a lower fasting blood glucose and higher serum insulin level compared to the db/db mice. A homeostatic model assessment (HOMA) suggests the improvement of β-cell function contributes to the improvement in glycemic control in db/db-204−/− mice. Next, we examined the cellular proliferation and endoplasmic reticulum (ER) stress and found an increased frequency of proliferating cells (PCNA + ve) and a decreased CHOP expression in the islets of db/db-204−/− mice. Next, we determined the effect of systemic miR-204 inhibition in improving glycemic control in the high-fat diet (HFD)-fed insulin-resistant mice. MiR-204 inhibition for 6 weeks improved the HFD-triggered impairment in glucose disposal. In conclusion, the absence of miR-204 improves β-cell proliferation, decreases islet ER stress, and improves glycemic control with limited change in body weight in obese mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect