title: Impaired insulin secretion in four Tangier disease patients with ABCA1 mutations.
abstract: OBJECTIVE
  Tangier disease (TD), caused by deficiency of ATP-binding cassette transporter A1, is characterized by the absence of high density lipoprotein and the accumulation of cholesteryl esters in many tissues. Recently, it has been reported that ABCA1 is expressed in pancreatic beta cells and mice with specific inactivation of ABCA1 in beta cells showed markedly impaired insulin secretion, suggesting that ABCA1 deficiency may be involved in diabetes. The aim of the current study was to confirm these findings by the oral glucose tolerance test (OGTT) in human subjects with ABCA1 deficiency.
  
  
  RESULTS
  Four Japanese patients with TD were investigated by OGTT with 75 g glucose. In all TD patients, the plasma glucose concentration after 30 min progressively increased, indicating a type 2 diabetic pattern; however the plasma insulin concentration did not respond well to glucose increase. The calculated insulinogenic index was significantly lower in TD patients than in non-diabetic controls (0.055+/-0.034 vs 0.775+/-0.538, mean+/-SD, p<0.05, respectively).
  
  
  CONCLUSIONS
  Although the number of TD patients was very small in the current study, these observations indicated a possible mechanism that glucose-stimulated insulin secretion might be impaired in human TD patients with ABCA1 mutations. Taken together, ABCA1 may be involved in insulin secretion from pancreatic beta-cells.
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan. koseki@imed2.med.osaka-u.ac.jp
authors: Masahiro
authors: M
authors: Koseki
authors: Akifumi
authors: A
authors: Matsuyama
authors: Kazuhiro
authors: K
authors: Nakatani
authors: Miwako
authors: M
authors: Inagaki
authors: Hajime
authors: H
authors: Nakaoka
authors: Ryota
authors: R
authors: Kawase
authors: Miyako
authors: M
authors: Yuasa-Kawase
authors: Kazumi
authors: K
authors: Tsubakio-Yamamoto
authors: Daisaku
authors: D
authors: Masuda
authors: Jose C
authors: JC
authors: Sandoval
authors: Tohru
authors: T
authors: Ohama
authors: Yumiko
authors: Y
authors: Nakagawa-Toyama
authors: Fumihiko
authors: F
authors: Matsuura
authors: Makoto
authors: M
authors: Nishida
authors: Masato
authors: M
authors: Ishigami
authors: Ken-ichi
authors: K
authors: Hirano
authors: Naoki
authors: N
authors: Sakane
authors: Yoshitaka
authors: Y
authors: Kumon
authors: Tadashi
authors: T
authors: Suehiro
authors: Tadashi
authors: T
authors: Nakamura
authors: Iichiro
authors: I
authors: Shimomura
authors: Shizuya
authors: S
authors: Yamashita
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D001786:Blood Glucose; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013631:Tangier Disease / Q000097:blood / Q000235:genetics*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D007328:Insulin; D005947:Glucose