FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2301941246> ?p ?o ?g. }

• W2301941246 abstract "The capacity of pancreatic β cells to maintain glucose homeostasis during chronic physiologic and immunologic stress is important for cellular and metabolic homeostasis. Insulin receptor substrate 2 (IRS2) is a regulated adapter protein that links the insulin and IGF1 receptors to downstream signaling cascades. Since strategies to maintain or increase IRS2 expression can promote β cell growth, function, and survival, we conducted a screen to find small molecules that can increase IRS2 mRNA in isolated human pancreatic islets. We identified 77 compounds, including 15 that contained a tricyclic core. To establish the efficacy of our approach, one of the tricyclic compounds, trimeprazine tartrate, was investigated in isolated human islets and in mouse models. Trimeprazine is a first-generation antihistamine that acts as a partial agonist against the histamine H1 receptor (H1R) and other GPCRs, some of which are expressed on human islets. Trimeprazine promoted CREB phosphorylation and increased the concentration of IRS2 in islets. IRS2 was required for trimeprazine to increase nuclear Pdx1, islet mass, β cell replication and function, and glucose tolerance in mice. Moreover, trimeprazine synergized with anti-CD3 Abs to reduce the progression of diabetes in NOD mice. Finally, it increased the function of human islet transplants in streptozotocin-induced (STZ-induced) diabetic mice. Thus, trimeprazine, its analogs, or possibly other compounds that increase IRS2 in islets and β cells without adverse systemic effects might provide mechanism-based strategies to prevent the progression of diabetes." @default.
• W2301941246 created "2016-06-24" @default.
• W2301941246 creator A5003947228 @default.
• W2301941246 creator A5008915190 @default.
• W2301941246 creator A5031317524 @default.
• W2301941246 creator A5035292581 @default.
• W2301941246 creator A5042732133 @default.
• W2301941246 creator A5048092515 @default.
• W2301941246 creator A5049816813 @default.
• W2301941246 creator A5054486557 @default.
• W2301941246 creator A5057323526 @default.
• W2301941246 creator A5070508954 @default.
• W2301941246 creator A5075889141 @default.
• W2301941246 creator A5087833336 @default.
• W2301941246 creator A5091849779 @default.
• W2301941246 date "2016-03-17" @default.
• W2301941246 modified "2023-10-09" @default.
• W2301941246 title "Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice" @default.
• W2301941246 cites W1495740709 @default.
• W2301941246 cites W1507426115 @default.
• W2301941246 cites W1697523131 @default.
• W2301941246 cites W1833314573 @default.
• W2301941246 cites W1891972130 @default.
• W2301941246 cites W1966143184 @default.
• W2301941246 cites W1978107636 @default.
• W2301941246 cites W1983796537 @default.
• W2301941246 cites W1984364648 @default.
• W2301941246 cites W1988654590 @default.
• W2301941246 cites W2002973634 @default.
• W2301941246 cites W2005393609 @default.
• W2301941246 cites W2006836104 @default.
• W2301941246 cites W2015393683 @default.
• W2301941246 cites W2015413597 @default.
• W2301941246 cites W2018740895 @default.
• W2301941246 cites W2021521791 @default.
• W2301941246 cites W2026081908 @default.
• W2301941246 cites W2032218738 @default.
• W2301941246 cites W2039312493 @default.
• W2301941246 cites W2040936935 @default.
• W2301941246 cites W2043958887 @default.
• W2301941246 cites W2044660283 @default.
• W2301941246 cites W2045017910 @default.
• W2301941246 cites W2054222787 @default.
• W2301941246 cites W2056126151 @default.
• W2301941246 cites W2059743234 @default.
• W2301941246 cites W2060275191 @default.
• W2301941246 cites W2062219277 @default.
• W2301941246 cites W2064370574 @default.
• W2301941246 cites W2064417575 @default.
• W2301941246 cites W2068243889 @default.
• W2301941246 cites W2082137006 @default.
• W2301941246 cites W2082466457 @default.
• W2301941246 cites W2085119605 @default.
• W2301941246 cites W2086762191 @default.
• W2301941246 cites W2086862557 @default.
• W2301941246 cites W2089250607 @default.
• W2301941246 cites W2090830096 @default.
• W2301941246 cites W2094177994 @default.
• W2301941246 cites W2097952652 @default.
• W2301941246 cites W2105595222 @default.
• W2301941246 cites W2107818841 @default.
• W2301941246 cites W2114992052 @default.
• W2301941246 cites W2115383202 @default.
• W2301941246 cites W2117793740 @default.
• W2301941246 cites W2130102556 @default.
• W2301941246 cites W2130663011 @default.
• W2301941246 cites W2132511649 @default.
• W2301941246 cites W2137447062 @default.
• W2301941246 cites W2140213275 @default.
• W2301941246 cites W2146921827 @default.
• W2301941246 cites W2148479818 @default.
• W2301941246 cites W2149513114 @default.
• W2301941246 cites W2151402189 @default.
• W2301941246 cites W2151409811 @default.
• W2301941246 cites W2155702842 @default.
• W2301941246 cites W2157223171 @default.
• W2301941246 cites W2165991181 @default.
• W2301941246 cites W2166030247 @default.
• W2301941246 cites W2169537091 @default.
• W2301941246 cites W2172266085 @default.
• W2301941246 cites W2330166018 @default.
• W2301941246 cites W2425256690 @default.
• W2301941246 cites W73610930 @default.
• W2301941246 doi "https://doi.org/10.1172/jci.insight.80749" @default.
• W2301941246 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4854304" @default.
• W2301941246 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27152363" @default.
• W2301941246 hasPublicationYear "2016" @default.
• W2301941246 type Work @default.
• W2301941246 sameAs 2301941246 @default.
• W2301941246 citedByCount "7" @default.
• W2301941246 countsByYear W23019412462017 @default.
• W2301941246 countsByYear W23019412462018 @default.
• W2301941246 countsByYear W23019412462020 @default.
• W2301941246 countsByYear W23019412462021 @default.
• W2301941246 countsByYear W23019412462022 @default.
• W2301941246 crossrefType "journal-article" @default.
• W2301941246 hasAuthorship W2301941246A5003947228 @default.
• W2301941246 hasAuthorship W2301941246A5008915190 @default.
• W2301941246 hasAuthorship W2301941246A5031317524 @default.
• W2301941246 hasAuthorship W2301941246A5035292581 @default.

• next