Journal article
Genetic deletion of miR-204 improves glycemic control despite obesity in db/db mice
Biochemical and biophysical research communications, Vol.532(2), pp.167-172
11/05/2020
DOI: 10.1016/j.bbrc.2020.08.077
PMCID: PMC7808551
PMID: 32950230
Abstract
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. (C) 2020 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- Genetic deletion of miR-204 improves glycemic control despite obesity in db/db mice
- Creators
- Ravinder Reddy Gaddam - University of IowaYoung-Rae Kim - University of IowaQuixia Li - Roy J. and Lucille A. Carver College of MedicineJulia S. Jacobs - Roy J. and Lucille A. Carver College of MedicineMohanad Gabani - Roy J. and Lucille A. Carver College of MedicineAkansha Mishra - University of IowaJoseph A. Promes - University of IowaYumi Imai - Roy J. and Lucille A. Carver College of MedicineKaikobad Irani - Roy J. and Lucille A. Carver College of MedicineAjit Vikram - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Biochemical and biophysical research communications, Vol.532(2), pp.167-172
- DOI
- 10.1016/j.bbrc.2020.08.077
- PMID
- 32950230
- PMCID
- PMC7808551
- NLM abbreviation
- Biochem Biophys Res Commun
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- Publisher
- Elsevier
- Number of pages
- 6
- Grant note
- 18CDA34080125; 19POST34380127 / American Heart Association (AHA); American Heart Association R01-DK090490 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 11/05/2020
- Academic Unit
- Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984313071702771
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