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HDL and LDL cholesterol significantly influence β-cell function in type 2 diabetes mellitus

Kruit, Janine Ka; Brunham, Liam Ra; Verchere, C Bruceb; Hayden, Michael Ra

Current Opinion in Lipidology: June 2010 - Volume 21 - Issue 3 - p 178–185
doi: 10.1097/MOL.0b013e328339387b
Lipid metabolism: Edited by Jeffrey S. Cohn
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Purpose of review Patients with type 2 diabetes mellitus (T2DM) display significant abnormalities in both LDL and HDL particles. Recent data suggest that these changes in lipoprotein particles could contribute to the pathogenesis of T2DM. In this review, we focus on these abnormalities and discuss their possible impact on β-cell function and β-cell mass.

Recent findings Infusion of reconstituted HDL in T2DM patients improves β-cell function, whereas carriers of loss-of-function mutations in the cholesterol transporter ABCA1, who have decreased HDL levels, have impaired β-cell function. In addition, recent studies show that HDL protects against stress-induced β-cell apoptosis in vitro. Finally, increasing evidence points to a role for islet inflammation in the pathogenesis of T2DM. ABCA1 and ABCG1 may also modulate these inflammatory responses, suggesting an additional pathway by which HDL may impact T2DM.

Summary Recent findings indicate that HDL protects β-cells from cholesterol-induced β-cell dysfunction, stress-induced apoptosis and islet inflammation. As the protective properties of HDL are compromised in patients with metabolic syndrome and T2DM, dysfunctional HDL metabolism could contribute to the pathogenesis of T2DM. Therapeutic normalization of both the quantity and quality of HDL particles may be a novel approach to prevent or treat T2DM.

aDepartment of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Canada

bDepartments of Surgery and Pathology & Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence to Michael R. Hayden, Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 West 28th Avenue, Room 3026, Vancouver, BC V5Z 4H4, Canada Tel: +1 604 875 3535; fax: +1 604 875 3819; e-mail: mrh@cmmt.ubc.ca

© 2010 Lippincott Williams & Wilkins, Inc.