Abstract:
:Cellular cholesterol homeostasis is important for normal β-cell function. Disruption of cholesterol transport by decreased function of the ATP-binding cassette (ABC) transporter ABCA1 results in impaired insulin secretion. Mice lacking β-cell ABCA1 have increased islet expression of ABCG1, another cholesterol transporter implicated in β-cell function. To determine whether ABCA1 and ABCG1 have complementary roles in β-cells, mice lacking ABCG1 and β-cell ABCA1 were generated and glucose tolerance, islet sterol levels, and β-cell function were assessed. Lack of both ABCG1 and β-cell ABCA1 resulted in increased fasting glucose levels and a greater impairment in glucose tolerance compared with either ABCG1 deletion or loss of ABCA1 in β-cells alone. In addition, glucose-stimulated insulin secretion was decreased and sterol accumulation increased in islets lacking both transporters compared with those isolated from knockout mice with each gene alone. Combined deficiency of ABCA1 and ABCG1 also resulted in significant islet inflammation as indicated by increased expression of interleukin-1β and macrophage infiltration. Thus, lack of both ABCA1 and ABCG1 induces greater defects in β-cell function than deficiency of either transporter individually. These data suggest that ABCA1 and ABCG1 each make complimentary and important contributions to β-cell function by maintaining islet cholesterol homeostasis in vivo.
journal_name
Diabetesjournal_title
Diabetesauthors
Kruit JK,Wijesekara N,Westwell-Roper C,Vanmierlo T,de Haan W,Bhattacharjee A,Tang R,Wellington CL,LütJohann D,Johnson JD,Brunham LR,Verchere CB,Hayden MRdoi
10.2337/db11-1341subject
Has Abstractpub_date
2012-03-01 00:00:00pages
659-64issue
3eissn
0012-1797issn
1939-327Xpii
db11-1341journal_volume
61pub_type
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