@article{gharavy_sexually_2020,
	title = {Sexually dimorphic roles for the type 2 diabetes-associated {C2cd4b} gene in murine glucose homeostasis},
	copyright = {© 2020, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), CC BY-NC 4.0, as described at http://creativecommons.org/licenses/by-nc/4.0/},
	url = {https://www.biorxiv.org/content/10.1101/2020.05.18.099200v1},
	doi = {10.1101/2020.05.18.099200},
	abstract = {{\textless}h3{\textgreater}Abstract{\textless}/h3{\textgreater} {\textless}p{\textgreater}Variants close to the \textit{VPS13C/C2CD4A/C2CD4B} locus are associated with altered risk of type 2 diabetes in genome-wide association studies. Whilst previous functional work has suggested roles for \textit{VPS13C} and \textit{C2CD4A} in disease development, none has explored the role of \textit{C2CD4B}. Here, we show that systemic inactivation of \textit{C2cd4b} in mice leads to marked, but highly sexually dimorphic, changes in body weight and glucose homeostasis. Female \textit{C2cd4b} mice display unchanged body weight but abnormal glucose tolerance and defective \textit{in vivo,} but not \textit{in vitro,} insulin secretion, associated with a marked decrease in follicle stimulating hormone levels. In sharp contrast, male \textit{C2cd4b} null mice displayed normal glucose tolerance but an increase in body weight and fasting glycemia after maintenance on high fat diet. No metabolic disturbances were observed after global inactivation of \textit{C2cd4a} in mice, or in pancreatic β cell function at larval stages in \textit{C2cd4ab} null zebrafish. These studies suggest that \textit{C2cd4b} may act centrally to influence sex-dependent circuits which control pancreatic β cell function and glucose tolerance in rodents. However, the absence of sexual dimorphism in the impact of diabetes risk variants argues for additional roles for \textit{C2CD4A} or \textit{VPS13C} in the control of glucose homeostasis in man.{\textless}/p{\textgreater}},
	language = {en},
	urldate = {2020-08-03},
	journal = {bioRxiv},
	author = {Gharavy, S. Neda Mousavy and Owen, Bryn and Millership, Steven J. and Chabosseau, Pauline and Pizza, Grazia and Martinez-Sanchez, Aida and Tasoez, Emirhan and Georgiadou, Eleni and Hu, Ming and Fine, Nicholas H. F. and Jacobson, David A. and Dickerson, Matthew and Idevall-Hagren, Olof and Montoya, Alex and Kramer, Holger and Mehta, Zenobia and Withers, Dominic J. and Ninov, Nikolay and Gadue, Paul J. and Cardenas-Diaz, Fabian L. and Cruciani-Guglielmacci, Céline and Magnan, Christophe and Ibberson, Mark and Leclerc, Isabelle and Voz, Marianne and Rutter, Guy A.},
	month = may,
	year = {2020},
	note = {Publisher: Cold Spring Harbor Laboratory
Section: New Results},
	keywords = {WP4},
	pages = {2020.05.18.099200},
}