Stard10, a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) protein family, functions as a phospholipid transfer protein. It can bind and transfer phosphatidylcholine (PC) and phosphatidylethanolamine (PE), and is also involved in lipid-related pathways. Its overexpression has been associated with breast cancer, and genetic variants near STARD10 influence type 2 diabetes (T2D) risk, indicating its biological importance in disease-related processes [1,2].

In mice, β-cell-selective deletion of StarD10 led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion, recapitulating the pattern of improved proinsulin processing observed in human T2D-risk allele carriers [2]. Stard10 knockout mice also showed altered bile acid homeostasis, with increased biliary secretion of bile acids and lower levels of secondary bile acids in the liver, suggesting impaired enterohepatic cycling. This was accompanied by down-regulation of PPARα-dependent genes responsible for bile acid metabolism [3].

In conclusion, Stard10 plays crucial roles in lipid transfer, insulin secretion, and bile acid metabolism. Mouse knockout models have been instrumental in revealing its role in T2D-related insulin secretion defects and bile acid homeostasis, providing valuable insights into the underlying disease mechanisms [2,3].

References:

1. Olayioye, Monilola A, Vehring, Stefanie, Müller, Peter, Visvader, Jane E, Pomorski, Thomas. 2005. StarD10, a START domain protein overexpressed in breast cancer, functions as a phospholipid transfer protein. In The Journal of biological chemistry, 280, 27436-42. doi:. https://pubmed.ncbi.nlm.nih.gov/15911624/

2. Carrat, Gaelle R, Hu, Ming, Nguyen-Tu, Marie-Sophie, McCarthy, Mark I, Rutter, Guy A. 2017. Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice. In American journal of human genetics, 100, 238-256. doi:10.1016/j.ajhg.2017.01.011. https://pubmed.ncbi.nlm.nih.gov/28132686/

3. Ito, Masanori, Yamanashi, Yoshihide, Toyoda, Yu, Takada, Tappei, Adachi-Akahane, Satomi. 2012. Disruption of Stard10 gene alters the PPARα-mediated bile acid homeostasis. In Biochimica et biophysica acta, 1831, 459-68. doi:10.1016/j.bbalip.2012.11.008. https://pubmed.ncbi.nlm.nih.gov/23200860/