Group 1B phospholipase A2-mediated lysophospholipid absorption directly contributes to postprandial hyperglycemia.
Postprandial hyperglycemia is an early indicator of abnormality in glucose metabolism leading to type 2 diabetes. However, mechanisms that contribute to postprandial hyperglycemia have not been identified. This study showed that mice with targeted inactivation of the group 1B phospholipase A2 (Pla2g1b) gene displayed lower postprandial glycemia than that observed in wild-type mice after being fed a glucose-rich meal. The difference was caused by enhanced postprandial glucose uptake by the liver, heart, and muscle tissues as well as altered postprandial hepatic glucose metabolism in the Pla2g1b-/- mice. These differences were attributed to a fivefold decrease in the amount of dietary phospholipids absorbed as lysophospholipids in Pla2g1b-/- mice compared with that observed in Pla2g1b+/+ mice. Elevating plasma lysophospholipid levels in Pla2g1b-/- mice via intraperitoneal injection resulted in glucose intolerance similar to that exhibited by Pla2g1b+/+ mice. Studies with cultured hepatoma cells revealed that lysophospholipids dose-dependently suppressed insulin-stimulated glycogen synthesis. These results demonstrated that reduction of lysophospholipid absorption enhances insulin-mediated glucose metabolism and is protective against postprandial hyperglycemia.
Department of Pathology, Genome Research Institute, University of Cincinnati, 2120 E. Galbraith Rd., Cincinnati, OH 45237-0507, USA.
Eric D
ED
Labonté
R Jason
RJ
Kirby
Nicholas M
NM
Schildmeyer
April M
AM
Cannon
Kevin W
KW
Huggins
David Y
DY
Hui
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism*; D007408:Intestinal Absorption / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010741:Phospholipases A / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D054467:Phospholipases A2; D019518:Postprandial Period
D017931:DNA Primers; D008246:Lysophospholipids; D010741:Phospholipases A; D054467:Phospholipases A2