| Title |
Estrogens Promote Misfolded Proinsulin Degradation to Protect Insulin Production and Delay Diabetes
|
|---|---|
| Published in |
Cell Reports, July 2018
|
| DOI | 10.1016/j.celrep.2018.06.019 |
| Pubmed ID | |
| Authors |
Beibei Xu, Camille Allard, Ana I. Alvarez-Mercado, Taylor Fuselier, Jun Ho Kim, Laurel A. Coons, Sylvia C. Hewitt, Fumihiko Urano, Kenneth S. Korach, Ellis R. Levin, Peter Arvan, Z. Elizabeth Floyd, Franck Mauvais-Jarvis |
| Abstract |
Conjugated estrogens (CE) delay the onset of type 2 diabetes (T2D) in postmenopausal women, but the mechanism is unclear. In T2D, the endoplasmic reticulum (ER) fails to promote proinsulin folding and, in failing to do so, promotes ER stress and β cell dysfunction. We show that CE prevent insulin-deficient diabetes in male and in female Akita mice using a model of misfolded proinsulin. CE stabilize the ER-associated protein degradation (ERAD) system and promote misfolded proinsulin proteasomal degradation. This involves activation of nuclear and membrane estrogen receptor-α (ERα), promoting transcriptional repression and proteasomal degradation of the ubiquitin-conjugating enzyme and ERAD degrader, UBC6e. The selective ERα modulator bazedoxifene mimics CE protection of β cells in females but not in males. |
X Demographics
The data shown below were collected from the profiles of 66 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 9 | 14% |
| Spain | 7 | 11% |
| United Kingdom | 5 | 8% |
| Canada | 4 | 6% |
| France | 2 | 3% |
| Mexico | 2 | 3% |
| Venezuela, Bolivarian Republic of | 1 | 2% |
| Chile | 1 | 2% |
| Austria | 1 | 2% |
| Other | 4 | 6% |
| Unknown | 30 | 45% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 30 | 45% |
| Members of the public | 28 | 42% |
| Practitioners (doctors, other healthcare professionals) | 6 | 9% |
| Science communicators (journalists, bloggers, editors) | 1 | 2% |
| Unknown | 1 | 2% |
Mendeley readers
The data shown below were compiled from readership statistics for 79 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 79 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 17 | 22% |
| Student > Bachelor | 12 | 15% |
| Student > Doctoral Student | 8 | 10% |
| Researcher | 8 | 10% |
| Other | 5 | 6% |
| Other | 12 | 15% |
| Unknown | 17 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 25 | 32% |
| Medicine and Dentistry | 15 | 19% |
| Agricultural and Biological Sciences | 11 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
| Immunology and Microbiology | 3 | 4% |
| Other | 5 | 6% |
| Unknown | 17 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 33. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 May 2022.
All research outputs
#1,212,612
of 25,385,509 outputs
Outputs from Cell Reports
#2,801
of 12,965 outputs
Outputs of similar age
#25,738
of 341,606 outputs
Outputs of similar age from Cell Reports
#77
of 308 outputs
Altmetric has tracked 25,385,509 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,965 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 30.3. This one has done well, scoring higher than 78% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 341,606 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 92% of its contemporaries.
We're also able to compare this research output to 308 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 75% of its contemporaries.