HDL and LDL cholesterol significantly influence beta-cell function in type 2 diabetes mellitus.
OBJECTIVE
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 beta-cell function and beta-cell mass.


RESULTS
Infusion of reconstituted HDL in T2DM patients improves beta-cell function, whereas carriers of loss-of-function mutations in the cholesterol transporter ABCA1, who have decreased HDL levels, have impaired beta-cell function. In addition, recent studies show that HDL protects against stress-induced beta-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.


CONCLUSIONS
Recent findings indicate that HDL protects beta-cells from cholesterol-induced beta-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.
Kruit
Janine K
JK
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Brunham
Liam R
LR
Verchere
C Bruce
CB
Hayden
Michael R
MR
D000818:Animals; D002470:Cell Survival; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL