Comment on Rickels et al. Loss-of-Function Mutations in ABCA1 and Enhanced β-Cell Secretory Capacity in Young Adults. Diabetes 2015;64:193-199.

Abstract

We read with great interest the recent article by Rickels et al. (1) on the enhancement of β-cell secretory capacity in young adults with Tangier disease (TD) (MIM 205400). The association of type 1 diabetes and type 2 diabetes (T2D) with reduced levels of circulating HDL cholesterol has been recognized since the early 1980s. In 2007, we identified the critical relationship between the ABCA1-mediated regulation of intracellular cholesterol levels in β-cells and insulin secretory capacity (2). At a mechanistic level, we identified that excessive cholesterol interrupts the depolarization-induced exocytotic fusion of insulin granules in β-cells (3). Work from our laboratory and others confirmed that carriers of loss-of-function mutations in the ABCA1 gene have dysfunctional β-cells (4), a finding that …