E-viri
Recenzirano
Odprti dostop
-
Zhang, Xin; Wang, Xiaowen; Yuan, Ziqiang; Radford, Sarah J.; Liu, Chen; Libutti, Steven K.; Zheng, X.F. Steven
Cell reports, 03/2021, Letnik: 34, Številka: 11Journal Article
Rab1A is a small GTPase known for its role in vesicular trafficking. Recent evidence indicates that Rab1A is essential for amino acids (aas) sensing and signaling to regulate mTORC1 in normal and cancer cells. However, Rab1A’s in vivo function in mammals is not known. Here, we report the generation of tamoxifen (TAM)-induced whole body Rab1A knockout (Rab1A−/−) in adult mice. Rab1A−/− mice are viable but become hyperglycemic and glucose intolerant due to impaired insulin transcription and β-cell proliferation and maintenance. Mechanistically, Rab1A mediates AA-mTORC1 signaling, particularly branched chain amino acids (BCAA), to regulate the stability and localization of the insulin transcription factor Pdx1. Collectively, these results reveal a physiological role of aa-Rab1A-mTORC1 signaling in the control of whole-body glucose homeostasis in mammals. Intriguingly, Rab1A expression is reduced in β-cells of type 2 diabetes (T2D) patients, which is correlated with loss of insulin expression, suggesting that Rab1A downregulation contributes to T2D progression. Display omitted •Rab1A regulates mTORC1 signaling in response to amino acids (aas) in beta-cells•Rab1A knockout mice are deficient of insulin expression and hyperglycemic•Branched chain aas regulate insulin transcription through mTORC1-Rab1A-PDX1 axis•Amino acids regulate beta-cell trans-differentiation through mTORC1-Rab1A-PDX1 axis Zhang et al. generate and analyze inducible Rab1A knockout mice. The results reveal that Rab1A-mTORC1 mediates branched chain amino acids signaling and regulates PDX-dependent insulin transcription and beta-cell trans-differentiation to alpha-cells. This amino acid sensing and signaling mechanism controls whole-body glucose homeostasis in mice and men.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.