{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:33:56Z","timestamp":1790231636354,"version":"4.1.0"},"reference-count":21,"publisher":"American Diabetes Association","issue":"1","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,1,1]]},"abstract":"<jats:p>Loss-of-function mutations affecting the cholesterol transporter ATP-binding cassette transporter subfamily A member 1 (ABCA1) impair cellular cholesterol efflux and are associated with reduced HDL-cholesterol (HDL-C) levels. ABCA1 may also be important in regulating \u03b2-cell cholesterol homeostasis and insulin secretion. We sought to determine whether loss-of-function ABCA1 mutations affect \u03b2-cell secretory capacity in humans by performing glucose-potentiated arginine tests in three subjects homozygous for ABCA1 mutations (age 25 \u00b1 11 years), eight heterozygous subjects (28 \u00b1 7 years), and eight normal control subjects pair-matched to the heterozygous carriers. To account for any effect of low HDL-C on insulin secretion, we studied nine subjects with isolated low HDL-C with no ABCA1 mutations (age 26 \u00b1 6 years) and nine pair-matched control subjects. Homozygotes for ABCA1 mutations exhibited enhanced oral glucose tolerance and dramatically increased \u03b2-cell secretory capacity that was also greater in ABCA1 heterozygous subjects than in control subjects, with no differences in insulin sensitivity. Isolated low HDL-C subjects also demonstrated an increase in \u03b2-cell secretory capacity but in contrast to those with ABCA1 mutations, exhibited impaired insulin sensitivity, supporting \u03b2-cell compensation for increased insulin demand. These data indicate that loss-of-function mutations in ABCA1 in young adults may be associated with enhanced \u03b2-cell secretory capacity and normal insulin sensitivity and support the importance of cellular cholesterol homeostasis in regulating \u03b2-cell insulin secretion.<\/jats:p>","DOI":"10.2337\/db14-0436","type":"journal-article","created":{"date-parts":[[2014,8,15]],"date-time":"2014-08-15T13:05:09Z","timestamp":1408107909000},"page":"193-199","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":31,"title":["Loss-of-Function Mutations in <i>ABCA1<\/i> and Enhanced \u03b2-Cell Secretory Capacity in Young Adults"],"prefix":"10.2337","volume":"64","author":[{"given":"Michael R.","family":"Rickels","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 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