| First Author | Gaddam RR | Year | 2020 |
| Journal | Biochem Biophys Res Commun | Volume | 532 |
| Issue | 2 | Pages | 167-172 |
| PubMed ID | 32950230 | Mgi Jnum | J:304265 |
| Mgi Id | MGI:6694712 | Doi | 10.1016/j.bbrc.2020.08.077 |
| Citation | Gaddam RR, et al. (2020) Genetic deletion of miR-204 improves glycemic control despite obesity in db/db mice. Biochem Biophys Res Commun 532(2):167-172 |
| abstractText | 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 beta-cell function. The miR-204 is highly expressed in the beta-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 beta-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 beta-cell proliferation, decreases islet ER stress, and improves glycemic control with limited change in body weight in obese mice. |
