Lipocalin-type prostaglandin D(2) synthase stimulates glucose transport via enhanced GLUT4 translocation.
Previously, we demonstrated that lipocalin-type prostaglandin D(2) synthase (L-PGDS) knockout mice become glucose intolerant and display signs of diabetic nephropathy and accelerated atherosclerosis. In the current study we sought to explain the link between L-PGDS and glucose tolerance. Using the insulin-sensitive rat skeletal muscle cell line, L6, we showed that L-PGDS could stimulate glucose transport approximately 2-fold as well as enhance insulin-stimulated glucose transport, as measured by 2-deoxy-[(3)H]-glucose uptake. The increased glucose transport was not attributed to increased GLUT4 production but rather the stimulation of GLUT4 translocation to the plasma membrane, a phenomenon that was lost when cells were cultured under hyperglycemic (20 mM) conditions or pretreated with wortmannin. There was however, an increase in GLUT1 expression as well as a 3-fold increase in hexokinase III expression, which was increased to nearly 5-fold in the presence of insulin, in response to L-PGDS at 20 mM glucose. In addition, adipocytes isolated from L-PGDS knockout mice were significantly less sensitive to insulin-stimulated glucose transport than wild-type. We conclude that L-PGDS, via production of prostaglandin D(2), is an important mediator of muscle and adipose glucose transport which is modulated by glycemic conditions and plays a significant role in the glucose intolerance associated with type 2 diabetes.
Ragolia
Louis
L
Vascular Biology Institute, Winthrop-University Hospital, Mineola, NY 11501, USA. LRagolia@Winthrop.org
Hall
Christopher E
CE
Palaia
Thomas
T
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D003920:Diabetes Mellitus / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000378:metabolism*; D054834:Lipocalins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015230:Prostaglandin D2 / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction
D051275:Glucose Transporter Type 4; D007328:Insulin; D054834:Lipocalins; D019869:Phosphatidylinositol 3-Kinases; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D005947:Glucose; D015230:Prostaglandin D2