The ATP-binding cassette transporter subfamily A member 1 (ABC-A1) and type 2 diabetes: an association beyond HDL cholesterol.
Recent findings from several groups demonstrate that ABC-A1 participates in the pathogenesis of the metabolic syndrome and type 2 diabetes. A variant of the ABC-A1 gene (R230C) is associated with the metabolic syndrome and its co-morbidities in Mexicans. Its presence is associated with an increased risk for obesity, the metabolic syndrome and type 2 diabetes. R230C is found exclusively in Amerindian and Amerindian-derived populations. Moreover, animal models confirm the participation of ABC-A1 in the pathogenesis of diabetes. Mice lacking AbcA1 specifically in beta cells had glucose intolerance at 8 weeks of age. The absence of ABC-A1 led to cholesterol accumulation within the beta cell plasma membrane, suggesting that cholesterol may play a role in the insulin secretory pathway. In conclusion, ABC-A1 may be more than a determinant of HDL-cholesterol. It may provide a link between components of the metabolic syndrome and atherosclerosis.
Salinas
Carlos A Aguilar
CA
Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico. caguilarsalinas@yahoo.com
Cruz-Bautista
Ivette
I
Mehta
Roopa
R
Villarreal-Molina
Ma T
MT
Pérez
Francisco J G
FJ
Tusié-Luna
Ma T
MT
Canizales-Quinteros
Samuel
S
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D019943:Amino Acid Substitution; D016632:Apolipoprotein A-I / Q000097:blood / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D020641:Polymorphism, Single Nucleotide
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL