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Showing 1 to 12 of 12 entries
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10 Years of GWAS Discovery: Biology, Function, and Translation.

American journal of human genetics

Visscher PM, Wray NR, Zhang Q, Sklar P, McCarthy MI, Brown MA, Yang J.
PMID: 28686856
Am J Hum Genet. 2017 Jul 06;101(1):5-22. doi: 10.1016/j.ajhg.2017.06.005.

Application of the experimental design of genome-wide association studies (GWASs) is now 10 years old (young), and here we review the remarkable range of discoveries it has facilitated in population and complex-trait genetics, the biology of diseases, and translation...

Analysis of Purified Pancreatic Islet Beta and Alpha Cell Transcriptomes Reveals 11β-Hydroxysteroid Dehydrogenase (Hsd11b1) as a Novel Disallowed Gene.

Frontiers in genetics

Pullen TJ, Huising MO, Rutter GA.
PMID: 28443133
Front Genet. 2017 Apr 10;8:41. doi: 10.3389/fgene.2017.00041. eCollection 2017.

We and others have previously identified a group of genes, dubbed "disallowed," whose expression is markedly lower in pancreatic islets than in other mammalian cell types. Forced mis-expression of several members of this family leads to defective insulin secretion,...

Mechanisms of Weight Loss After Obesity Surgery.

Endocrine reviews

Akalestou E, Miras AD, Rutter GA, le Roux CW.
PMID: 34363458
Endocr Rev. 2022 Jan 12;43(1):19-34. doi: 10.1210/endrev/bnab022.

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated...

Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study.

Diabetes

Slieker RC, Donnelly LA, Fitipaldi H, Bouland GA, Giordano GN, Åkerlund M, Gerl MJ, Ahlqvist E, Ali A, Dragan I, Elders P, Festa A, Hansen MK, van der Heijden AA, Mansour Aly D, Kim M, Kuznetsov D, Mehl F, Klose C, Simons K, Pavo I, Pullen TJ, Suvitaival T, Wretlind A, Rossing P, Lyssenko V, Legido Quigley C, Groop L, Thorens B, Franks PW, Ibberson M, Rutter GA, Beulens JWJ, 't Hart LM, Pearson ER.
PMID: 34376475
Diabetes. 2021 Nov;70(11):2683-2693. doi: 10.2337/db20-1281. Epub 2021 Aug 10.

Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of a previous study clustered people with diabetes according to five diabetes subtypes. The aim of the current study is to investigate the...

Mechanisms of weight loss after obesity surgery.

Endocrine reviews

Akalestou E, Miras AD, Rutter GA, le Roux CW.
PMID: 34363458
Endocr Rev. 2021 Aug 07; doi: 10.1210/endrev/bnab022. Epub 2021 Aug 07.

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but have since been linked to reduced appetitive behaviour and potentially increased energy expenditure. Implicated...

Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis.

Diabetologia

Mousavy Gharavy SN, Owen BM, Millership SJ, Chabosseau P, Pizza G, Martinez-Sanchez A, Tasoez E, Georgiadou E, Hu M, Fine NHF, Jacobson DA, Dickerson MT, Idevall-Hagren O, Montoya A, Kramer H, Mehta Z, Withers DJ, Ninov N, Gadue PJ, Cardenas-Diaz FL, Cruciani-Guglielmacci C, Magnan C, Ibberson M, Leclerc I, Voz M, Rutter GA.
PMID: 33492421
Diabetologia. 2021 Apr;64(4):850-864. doi: 10.1007/s00125-020-05350-x. Epub 2021 Jan 25.

AIMS/HYPOTHESIS: Variants close to the VPS13C/C2CD4A/C2CD4B locus are associated with altered risk of type 2 diabetes in genome-wide association studies. While previous functional work has suggested roles for VPS13C and C2CD4A in disease development, none has explored the role...

Mechanisms of Weight Loss After Obesity Surgery.

Endocrine reviews

Akalestou E, Miras AD, Rutter GA, le Roux CW.
PMID: 34363458
Endocr Rev. 2022 Jan 12;43(1):19-34. doi: 10.1210/endrev/bnab022.

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated...

The Influence of Peptide Context on Signaling and Trafficking of Glucagon-like Peptide-1 Receptor Biased Agonists.

ACS pharmacology & translational science

Fang Z, Chen S, Pickford P, Broichhagen J, Hodson DJ, Corrêa IR, Kumar S, Görlitz F, Dunsby C, French PMW, Rutter GA, Tan T, Bloom SR, Tomas A, Jones B.
PMID: 32296773
ACS Pharmacol Transl Sci. 2020 Mar 17;3(2):345-360. doi: 10.1021/acsptsci.0c00022. eCollection 2020 Apr 10.

Signal bias and membrane trafficking have recently emerged as important considerations in the therapeutic targeting of the glucagon-like peptide-1 receptor (GLP-1R) in type 2 diabetes and obesity. In the present study, we have evaluated a peptide series with varying...

A CRISPR/Cas9 genome editing pipeline in the EndoC-βH1 cell line to study genes implicated in beta cell function.

Wellcome open research

Grotz AK, Abaitua F, Navarro-Guerrero E, Hastoy B, Ebner D, Gloyn AL.
PMID: 31976379
Wellcome Open Res. 2020 Apr 29;4:150. doi: 10.12688/wellcomeopenres.15447.2. eCollection 2019.

Type 2 diabetes (T2D) is a global pandemic with a strong genetic component, but most causal genes influencing the disease risk remain unknown. It is clear, however, that the pancreatic beta cell is central to T2D pathogenesis.

Adipocyte-specific deletion of Tcf7l2 induces dysregulated lipid metabolism and impairs glucose tolerance in mice.

Diabetologia

Nguyen-Tu MS, Martinez-Sanchez A, Leclerc I, Rutter GA, da Silva Xavier G.
PMID: 33068125
Diabetologia. 2021 Jan;64(1):129-141. doi: 10.1007/s00125-020-05292-4. Epub 2020 Oct 17.

AIMS/HYPOTHESIS: Transcription factor 7-like 2 (TCF7L2) is a downstream effector of the Wnt/β-catenin signalling pathway implicated in type 2 diabetes risk through genome-wide association studies. Although its expression is critical for adipocyte development, the potential roles of changes in...

Mechanisms of Weight Loss After Obesity Surgery.

Endocrine reviews

Akalestou E, Miras AD, Rutter GA, le Roux CW.
PMID: 34363458
Endocr Rev. 2022 Jan 12;43(1):19-34. doi: 10.1210/endrev/bnab022.

Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated...

Dysregulation of the Pdx1/Ovol2/Zeb2 axis in dedifferentiated β-cells triggers the induction of genes associated with epithelial-mesenchymal transition in diabetes.

Molecular metabolism

de Jesus DS, Mak TCS, Wang YF, von Ohlen Y, Bai Y, Kane E, Chabosseau P, Chahrour CM, Distaso W, Salem V, Tomas A, Stoffel M, Rutter GA, Latreille M.
PMID: 33989778
Mol Metab. 2021 Nov;53:101248. doi: 10.1016/j.molmet.2021.101248. Epub 2021 May 12.

OBJECTIVE: β-cell dedifferentiation has been revealed as a pathological mechanism underlying pancreatic dysfunction in diabetes. We previously showed that increased miR-7 levels trigger β-cell dedifferentiation and diabetes. We used β-cell-specific miR-7 overexpressing mice (Tg7) to test the hypothesis that...

Showing 1 to 12 of 12 entries