ISSN 1662-4009 (online)

ey0021.10-7 | New Paradigms | ESPEYB21

10.7. Heterogeneity and endotypes in type 1 diabetes mellitus

MJ Redondo , NG Morgan

Brief Summary: This review describes the heterogeneity in type 1 diabetes (T1D), the emerging concept of endotypes, and their impact on T1D prediction, prevention and treatment.Growing evidence supports the existence of heterogeneity in T1D genetic background, pathogenesis, clinical course, susceptibility to complications and response to emerging immunotherapy (1,2). This has led to the concept that T1D is not a single disease; instead there are distinct...

ey0021.5-13 | Novel Treatments | ESPEYB21

5.13. Low-dose infigratinib increases bone growth and corrects growth plate abnormalities in an achondroplasia mouse model

Demuynck Benoit , Flipo Justine , Kaci Nabil , Dambkowski Carl , Paull Morgan , Muslimova Elena , Shah Bhavik P. , Legeai-Mallet Laurence

In brief: This study investigated the effect of infigratinib, a selective and orally bioavailable FGFR1-3 inhibitor, administered at different doses or according to different dosing regimens, on bone growth in a mouse model mimicking achondroplasia (Fgfr3Y367C/+). This study was partially sponsored by a grant from BridgeBio/QED Therapeutics.Commentary: Achondroplasia is one of the most common constitutional bone diseases (> 300,000 affecte...

ey0018.14-3 | (1) | ESPEYB18

14.3. Decreasing body lengths in North Atlantic right whales

Stewart Joshua D , Durban John W , Knowlton Amy R , Lynn Morgan S , Fearnbach Holly , Barbaro Jacob , Perryman Wayne L , Miller Carolyn A , Moore Michael J

Current Biology 2021 May 17;S0960-9822(21)00614-X. doi: https://doi.org/10.1016/j.cub.2021.04.067The North Atlantic right whale (Narwhale, NARW) is a medium-sized toothed whale that lives year-round in the Arctic waters around Greenland, Canada, and Russia. It possesses a large ‘tusk’ from a protruding canine tooth. NARW born in recent years have experienced stunted growth, and...

ey0019.10-7 | New paradigms | ESPEYB19

10.7. Circulating C-peptide levels in living children and young people and pancreatic beta cell loss in pancreas donors across type 1 diabetes disease duration

ALJ Carr , JRJ Inshaw , CS Flaxman , P Leete , RC Wyatt , LA Russell , M Palmer , D Prasolov , T Worthington , B Hull , LS Wicker , DB Dunger , RA Oram , NG Morgan , JA Todd , SJ Richardson , REJ Besser

Diabetes. 2022;71:1591-1596. https://pubmed.ncbi.nlm.nih.gov/35499624/Brief Summary: This cross-sectional study compared trends in plasma C-peptide decline in 4,076 young people with type 1 diabetes (T1D), with trends in beta-cell loss in 235 pancreas donors. As expected, C-peptide declined over time, and this was particularly marked in children with T1D younger than 7 years. Of interest, p...

ey0019.10-15 | Pathogenesis | ESPEYB19

10.15. Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes

M Fasolino , GW Schwartz , AR Patil , A Mongia , ML Golson , YJ Wang , A Morgan , C Liu , J Schug , J Liu , M Wu , D Traum , A Kondo , CL May , N Goldman , W Wang , M Feldman , JH Moore , AS Japp , MR Betts , Consortium HPAP , RB Faryabi , A Naji , KH Kaestner , G Vahedi

Nat Metab. 2022 Feb;4(2):284-299. https://pubmed.ncbi.nlm.nih.gov/35228745/Brief Summary: This study used three high-throughput single-cell technologies to generate a pancreatic islet cell atlas from 24 organ donors with type 1 diabetes (T1D), autoantibody positive and healthy donors. The most remarkable finding was that a subset of exocrine ductal cells appears to acquire a signature of to...

ey0020.13-8 | Section | ESPEYB20

13.8. Non-coding variants disrupting a tissue-specific regulatory element in HK1 cause congenital hyperinsulinism

MN Wakeling , NDL Owens , JR Hopkinson , MB Johnson , JAL Houghton , A Dastamani , CS Flaxman , RC Wyatt , TI Hewat , JJ Hopkins , TW Laver , R van Heugten , MN Weedon , E De Franco , KA Patel , S Ellard , NG Morgan , E Cheesman , I Banerjee , AT Hattersley , MJ Dunne , International Congenital Hyperinsulinism Consortium , SJ Richardson , SE Flanagan

In Brief: The authors performed whole genome sequencing on 135 patients with congenital hyperinsulinaemia (CHI) who had negative genetic testing for previously known CHI genes. They identified nine different non-coding de novo variants (carried by 14 probands) located in a regulatory region of HK1 intron 2 that co-segregated with disease in families.Comment: HK1 is a ‘disallowed gene’ in the liver and pancreatic beta cells. Th...

ey0015.14-14 | Reliable evidence on mouse knock-outs | ESPEYB15

14.14 Disease model discovery from 3,328 gene knockouts by The International Mouse Phenotyping Consortium

TF Meehan , N Conte , DB West , JO Jacobsen , J Mason , J Warren , CK Chen , I Tudose , M Relac , P Matthews , N Karp , L Santos , T Fiegel , N Ring , H Westerberg , S Greenaway , D Sneddon , H Morgan , GF Codner , ME Stewart , J Brown , N Horner , C International Mouse Phenotyping , M Haendel , N Washington , CJ Mungall , CL Reynolds , J Gallegos , V Gailus-Durner , T Sorg , G Pavlovic , LR Bower , M Moore , I Morse , X Gao , GP Tocchini-Valentini , Y Obata , SY Cho , JK Seong , J Seavitt , AL Beaudet , ME Dickinson , Y Herault , W Wurst , MH de Angelis , KCK Lloyd , AM Flenniken , LMJ Nutter , S Newbigging , C McKerlie , MJ Justice , SA Murray , KL Svenson , RE Braun , JK White , A Bradley , P Flicek , S Wells , WC Skarnes , DJ Adams , H Parkinson , AM Mallon , SDM Brown , D Smedley

To read the full abstract: Nat Genet 2017;49:1231-1238This large international initiative is a major collaboration across 25 research institutes that was set up as part of the scientific community’s response to concerns regarding the notoriously poor reproducibility of scientific research. Up to now, many mouse gene knock-outs have been made and reported, but inconsistency between finding...