In a paper published in Cell, researchers report a potential new approach for treating diabetes by protecting beta cells--the cells in the pancreas that produce, store and release the hormone insulin. When beta cells become dysfunctional, the body can't make insulin to control blood sugar (glucose) and levels of glucose can rise to dangerous--even fatal--levels.
The investigators accomplished their goal by using an unexpected source: vitamin D. Vitamin D in cells and mouse models proved beneficial in treating damaged beta cells. It also provided new insights about gene regulation that could be applied to developing treatments for other diseases, including cancer.
"We know that diabetes is a disease caused by inflammation," explains senior author. "In this study, we identified the vitamin D receptor as an important modulator of both inflammation and beta cell survival." Authors identify the vitamin D receptor (VDR) as a key modulator of inflammation and β cell survival.
Using beta cells created from embryonic stem cells, the investigators were able to identify a compound, iBRD9, that appeared to enhance the activation of the vitamin D receptor when it was combined with vitamin D to improve the survival of beta cells. The team accomplished this by conducting a screening test to look for compounds that improved the survival of beta cells in a dish. They then tested the combination in a mouse model of diabetes and showed that it could bring glucose back to normal levels in the animals.
"This study started out by looking at the role of vitamin D in beta cells," says the study's first author. "Epidemiological studies in patients have suggested a correlation between high vitamin D concentrations in the blood and a lower risk of diabetes, but the underlying mechanism was not well understood. It's been hard to protect beta cells with the vitamin alone. We now have some ideas about how we might be able to take advantage of this connection."
The underlying process has to do with transcription--the way that genes are translated into proteins. Combining the new compound with vitamin D allowed certain protective genes to be expressed at much higher levels than they are in diseased cells. Mechanistically, ligand (iBRD9) promotes VDR association with PBAF to effect genome-wide changes in chromatin accessibility and enhancer landscape, resulting in an anti-inflammatory response.
"Activating the vitamin D receptor can trigger the anti-inflammatory function of genes to help cells survive under stressed conditions," says co-corresponding author. "By using a screening system that we developed in the lab, we've been able to identify an important piece of that puzzle that allows for super-activation of the Vitamin D pathway."
"In this study, we looked at diabetes, but because this is an important receptor it could potentially be universal for any treatments where you need to boost the effect of vitamin D," adds one of the study's authors. "For example, we are especially interested in looking at it in pancreatic cancer, which is a disease that our lab already studies."
The investigators say that, although the new compound did not appear to cause any side effects in the mice, further testing is needed before clinical trials can begin.
https://www.salk.edu/news-release/boosting-the-effects-of-vitamin-d-to-tackle-diabetes/
https://www.cell.com/cell/fulltext/S0092-8674(18)30506-3
Boosting the effects of vitamin D to tackle diabetes
- 3,450 views
- Added
Edited
Latest News
Tumor infiltration of immun…
By newseditor
Posted 28 May
New light-controlled 'off s…
By newseditor
Posted 28 May
Gene function during embryo…
By newseditor
Posted 28 May
Formation of 3D blood vesse…
By newseditor
Posted 27 May
Liver regeneration during c…
By newseditor
Posted 27 May
Other Top Stories
Can low doses of alcohol prime brain for addiction?
Read more
Daytime eating prevents mood vulnerability in night work
Read more
Attention and running influence individual brain cells independently
Read more
The reason for brain dysfunction during warming
Read more
Computing odor identity in the olfactory system
Read more
Protocols
SEMORE: SEgmentation and MO…
By newseditor
Posted 26 May
Spatially resolved lipidomi…
By newseditor
Posted 24 May
Efficient expansion and CRI…
By newseditor
Posted 21 May
Massively parallel in vivo…
By newseditor
Posted 20 May
Breast cancer-on-chip for p…
By newseditor
Posted 16 May
Publications
Advanced microbiome therape…
By newseditor
Posted 29 May
Hippocampal astrocytes indu…
By newseditor
Posted 29 May
TNIK's emerging role in can…
By newseditor
Posted 29 May
Diabetes drugs activate neu…
By newseditor
Posted 29 May
Circadian tumor infiltratio…
By newseditor
Posted 28 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar