title: Effects of high-density lipoproteins on pancreatic beta-cell insulin secretion.
abstract: OBJECTIVE
  Type 2 diabetes is characterized by impaired beta-cell secretory function, insulin resistance, reduced high-density lipoprotein (HDL) levels, and increased cardiovascular risk. Given the current interest in therapeutic interventions that raise HDLs levels, this study investigates the effects of HDLs on insulin secretion from beta-cells.
  
  
  RESULTS
  Incubation of Min6 cells and primary islets under basal or high-glucose conditions with either apolipoprotein (apo) A-I or apoA-II in the lipid-free form, as a constituent of discoidal reconstituted HDLs (rHDLs), or with HDLs isolated from human plasma increased insulin secretion up to 5-fold in a calcium-dependent manner. The increase was time and concentration dependent. It was also K(ATP) channel and glucose metabolism dependent under high-glucose, but not low-glucose, conditions. The lipid-free apolipoprotein-mediated increase in insulin secretion was ATP binding cassette (ABC) transporter A1 and scavenger receptor-B1 dependent. The rHDL-mediated increase in insulin secretion was ABCG1 dependent. Exposure of beta-cells to lipid-free apolipoproteins also increased insulin mRNA expression and insulin secretion without significantly depleting intracellular insulin or cholesterol levels.
  
  
  CONCLUSIONS
  These results establish that lipid-free and lipid-associated apoA-I and apoA-II increase beta-cell insulin secretion and indicate that interventions that raise HDLs levels may be beneficial in type 2 diabetes.
authors.affiliation: The Heart Research Institute, Sydney, New South Wales, Australia.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Fryirs
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Mathiyalagan
authors.initials: M
authors.lastname: Appavoo
authors.forename: Bernard E
authors.initials: BE
authors.lastname: Tuch
authors.forename: Fatiha
authors.initials: F
authors.lastname: Tabet
authors.forename: Alison K
authors.initials: AK
authors.lastname: Heather
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D003981:Diazoxide / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D054086:KATP Channels / Q000819:agonists / Q000378:metabolism; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C487540:ABCG1 protein, mouse; C505693:APOA1 protein, human; C115794:APOA2 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D007328:Insulin; D054086:KATP Channels; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D005947:Glucose; D003981:Diazoxide; D002118:Calcium