Hepatic ABCA1 Expression Improves β-Cell Function and Glucose Tolerance

  1. Michael R. Hayden
  1. Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
  1. Corresponding author: Michael R. Hayden, mrh{at}cmmt.ubc.ca.

Abstract

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 β-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 β-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 β-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 β-cell function through both HDL production and interaction with β-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.

  • Received April 6, 2014.
  • Accepted July 10, 2014.

This Article

  1. Diabetes
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