Islet complex lipids: involvement in the actions of group VIA calcium-independent phospholipase A(2) in beta-cells.
The beta-isoform of group VIA calcium-independent phospholipase A(2) (iPLA(2)beta) does not require calcium for activation, is stimulated by ATP, and is sensitive to inhibition by a bromoenol lactone suicide substrate. Several potential functions have been proposed for iPLA(2)beta. Our studies indicate that iPLA(2)beta is expressed in beta-cells and participates in glucose-stimulated insulin secretion but is not involved in membrane phospholipid remodeling. If iPLA(2)beta plays a signaling role in glucose-stimulated insulin secretion, then conditions that impair iPLA(2)beta functions might contribute to the diminished capacity of beta-cells to secrete insulin in response to glucose, which is a prominent characteristic of type 2 diabetes. Our recent studies suggest that iPLA(2)beta might also participate in beta-cell proliferation and apoptosis and that various phospholipid-derived mediators are involved in these processes. Detailed characterization of the iPLA(2)beta protein level reveals that beta-cells express multiple isoforms of the enzyme, and our studies involve the hypothesis that different isoforms have different functions.
Ramanadham
Sasanka
S
Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.sramanad@im.wustl.edu
Song
Haowei
H
Bao
Shunzhong
S
Hsu
Fong-Fu
FF
Zhang
Sheng
S
Ma
Zhongmin
Z
Jin
Chun
C
Turk
John
J
D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000737:chemistry; D002118:Calcium / Q000502:physiology; D007515:Islets of Langerhans / Q000201:enzymology / Q000502:physiology*; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats
D017487:Ankyrins; D010743:Phospholipids; D010741:Phospholipases A; D002118:Calcium