| First Author | de Haan W | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 12 | Pages | 4076-82 |
| PubMed ID | 25028523 | Mgi Jnum | J:230124 |
| Mgi Id | MGI:5755542 | Doi | 10.2337/db14-0548 |
| Citation | de Haan W, et al. (2014) Hepatic ABCA1 expression improves beta-cell function and glucose tolerance. Diabetes 63(12):4076-82 |
| abstractText | Low HDL is a risk factor for the development of type 2 diabetes. Hepatic ABCA1 is the rate-limiting protein in HDL biogenesis, and mice lacking hepatic ABCA1 (ABCA1(-l/-l)) have very low plasma HDL concentrations. To investigate the role of hepatic ABCA1 in glucose tolerance and beta-cell function, we used ABCA1(-l/-l) mice, which showed impaired glucose tolerance without changes in insulin sensitivity. Insulin secretion was reduced following glucose gavage. Ex vivo, glucose stimulated insulin secretion from beta-cells from wild-type (WT) and ABCA1(-l/-l) mice was similar. Insulin secretion was, however, reduced upon addition of ABCA1(-l/-l) serum to the medium compared with WT serum, whereas islets lacking beta-cell ABCA1 were not affected differently by ABCA1(-l/-l) or WT serum. After high-fat feeding, WT and ABCA1(-l/-l) mice showed no difference in glucose tolerance or insulin secretion, and serum from ABCA1(-l/-l) and WT mice fed a high-fat diet did not affect insulin secretion differently. We conclude that hepatic ABCA1 improves glucose tolerance by improving beta-cell function through both HDL production and interaction with beta-cell ABCA1. The beneficial effect of hepatic ABCA1 is decreased under metabolic stress. Increasing hepatic ABCA1 may represent a novel therapeutic strategy for improving glucose homeostasis in diabetes. |
