Increased expression of GPI-specific phospholipase D in mouse models of type 1 diabetes.
Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a high-density lipoprotein-associated protein. However, the tissue source(s) for circulating GPI-PLD and whether serum levels are regulated are unknown. Because the diabetic state alters lipoprotein metabolism, and liver and pancreatic islets are possible sources of GPI-PLD, we hypothesized that GPI-PLD levels would be altered in diabetes. GPI-PLD serum activity and liver mRNA were examined in two mouse models of type 1 diabetes, a nonobese diabetic (NOD) mouse model and low-dose streptozotocin-induced diabetes in CD-1 mice. With the onset of hyperglycemia (2- to 5-fold increase over nondiabetic levels), GPI-PLD serum activity and liver mRNA increased 2- to 4-fold in both models. Conversely, islet expression of GPI-PLD was absent as determined by immunofluorescence. Insulin may regulate GPI-PLD expression, because insulin treatment of diabetic NOD mice corrected the hyperglycemia along with reducing serum GPI-PLD activity and liver mRNA. Our data demonstrate that serum GPI-PLD levels are altered in the diabetic state and are consistent with liver as a contributor to circulating GPI-PLD.
Deeg
M A
MA
Department of Medicine, Indiana University School of Medicine and the Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana 46202, USA. mdeeg@iupui.edu
Bowen
R F
RF
Williams
M D
MD
Olson
L K
LK
Kirk
E A
EA
LeBoeuf
R C
RC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009752:Nutritional Status; D010179:Pancreas / Q000473:pathology; D010641:Phenotype; D010739:Phospholipase D / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger; D010739:Phospholipase D; C065017:glycoprotein phospholipase D