Matches in SemOpenAlex for { <https://semopenalex.org/work/W2170480036> ?p ?o ?g. }
- W2170480036 endingPage "3049" @default.
- W2170480036 startingPage "3039" @default.
- W2170480036 abstract "Development of diabetes generally reflects an inadequate mass of insulin-producing beta-cells. beta-cell proliferation and differentiation are regulated by a variety of growth factors and hormones, including insulin-like growth factor I (IGF-I). GRF1 is a Ras-guanine nucleotide exchange factor known previously for its restricted expression in brain and its role in learning and memory. Here we demonstrate that GRF1 is also expressed in pancreatic islets. Interestingly, our GRF1-deficient mice exhibit reduced body weight, hypoinsulinemia and glucose intolerance owing to a reduction of beta-cells. Whereas insulin resistance is not detected in peripheral tissues, GRF1 knockout mice are leaner due to increased lipid catabolism. The reduction in circulating insulin does not reflect defective glucose sensing or insulin production but results from impaired beta-cell proliferation and reduced neogenesis. IGF-I treatment of isolated islets from GRF1 knockouts fails to activate critical downstream signals such as Akt and Erk. The observed phenotype is similar to manifestations of preclinical type 2 diabetes. Thus, our observations demonstrate a novel and specific role for Ras-GRF1 pathways in the development and maintenance of normal beta-cell number and function." @default.
- W2170480036 created "2016-06-24" @default.
- W2170480036 creator A5016379031 @default.
- W2170480036 creator A5020958574 @default.
- W2170480036 creator A5022029177 @default.
- W2170480036 creator A5041687603 @default.
- W2170480036 creator A5055948176 @default.
- W2170480036 creator A5061909361 @default.
- W2170480036 creator A5067139179 @default.
- W2170480036 creator A5086036956 @default.
- W2170480036 creator A5086894543 @default.
- W2170480036 creator A5089744207 @default.
- W2170480036 date "2003-06-16" @default.
- W2170480036 modified "2023-10-14" @default.
- W2170480036 title "Ras-GRF1 signaling is required for normal -cell development and glucose homeostasis" @default.
- W2170480036 cites W143471271 @default.
- W2170480036 cites W1493922188 @default.
- W2170480036 cites W1520222296 @default.
- W2170480036 cites W1544874562 @default.
- W2170480036 cites W1556383867 @default.
- W2170480036 cites W1624082697 @default.
- W2170480036 cites W1672592092 @default.
- W2170480036 cites W1675830194 @default.
- W2170480036 cites W1697523131 @default.
- W2170480036 cites W1794038664 @default.
- W2170480036 cites W1939450341 @default.
- W2170480036 cites W1984670510 @default.
- W2170480036 cites W1993163893 @default.
- W2170480036 cites W1996180957 @default.
- W2170480036 cites W2002639317 @default.
- W2170480036 cites W2004444822 @default.
- W2170480036 cites W2029149519 @default.
- W2170480036 cites W2031513892 @default.
- W2170480036 cites W2038982544 @default.
- W2170480036 cites W2045182106 @default.
- W2170480036 cites W2046278818 @default.
- W2170480036 cites W2049367666 @default.
- W2170480036 cites W2051541090 @default.
- W2170480036 cites W2052845309 @default.
- W2170480036 cites W2069597747 @default.
- W2170480036 cites W2076743657 @default.
- W2170480036 cites W2077689653 @default.
- W2170480036 cites W2082044596 @default.
- W2170480036 cites W2086082646 @default.
- W2170480036 cites W2100126797 @default.
- W2170480036 cites W2101926143 @default.
- W2170480036 cites W2103668981 @default.
- W2170480036 cites W2122603966 @default.
- W2170480036 cites W2133852124 @default.
- W2170480036 cites W2141160128 @default.
- W2170480036 cites W2151444325 @default.
- W2170480036 cites W2152166314 @default.
- W2170480036 cites W215315140 @default.
- W2170480036 cites W2159128174 @default.
- W2170480036 cites W2165110544 @default.
- W2170480036 cites W2407842216 @default.
- W2170480036 cites W2410813441 @default.
- W2170480036 cites W4244632188 @default.
- W2170480036 doi "https://doi.org/10.1093/emboj/cdg280" @default.
- W2170480036 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/162132" @default.
- W2170480036 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12805218" @default.
- W2170480036 hasPublicationYear "2003" @default.
- W2170480036 type Work @default.
- W2170480036 sameAs 2170480036 @default.
- W2170480036 citedByCount "83" @default.
- W2170480036 countsByYear W21704800362012 @default.
- W2170480036 countsByYear W21704800362013 @default.
- W2170480036 countsByYear W21704800362014 @default.
- W2170480036 countsByYear W21704800362015 @default.
- W2170480036 countsByYear W21704800362016 @default.
- W2170480036 countsByYear W21704800362017 @default.
- W2170480036 countsByYear W21704800362018 @default.
- W2170480036 countsByYear W21704800362019 @default.
- W2170480036 countsByYear W21704800362020 @default.
- W2170480036 countsByYear W21704800362021 @default.
- W2170480036 countsByYear W21704800362022 @default.
- W2170480036 countsByYear W21704800362023 @default.
- W2170480036 crossrefType "journal-article" @default.
- W2170480036 hasAuthorship W2170480036A5016379031 @default.
- W2170480036 hasAuthorship W2170480036A5020958574 @default.
- W2170480036 hasAuthorship W2170480036A5022029177 @default.
- W2170480036 hasAuthorship W2170480036A5041687603 @default.
- W2170480036 hasAuthorship W2170480036A5055948176 @default.
- W2170480036 hasAuthorship W2170480036A5061909361 @default.
- W2170480036 hasAuthorship W2170480036A5067139179 @default.
- W2170480036 hasAuthorship W2170480036A5086036956 @default.
- W2170480036 hasAuthorship W2170480036A5086894543 @default.
- W2170480036 hasAuthorship W2170480036A5089744207 @default.
- W2170480036 hasBestOaLocation W21704800362 @default.
- W2170480036 hasConcept C126322002 @default.
- W2170480036 hasConcept C134018914 @default.
- W2170480036 hasConcept C165220095 @default.
- W2170480036 hasConcept C2776828364 @default.
- W2170480036 hasConcept C2777391703 @default.
- W2170480036 hasConcept C2779306644 @default.
- W2170480036 hasConcept C2780093864 @default.
- W2170480036 hasConcept C3018667095 @default.
- W2170480036 hasConcept C55493867 @default.