Glucose and insulin regulate glycosylphosphatidylinositol-specific phospholipase D expression in islet beta cells.
Insulin resistance is associated with a compensatory islet hyperactivity to sustain adequate insulin biosynthesis and secretion to maintain near euglycemia. Both glucose and insulin are involved in regulating proteins required for insulin synthesis and secretion within the islet and islet hypertrophy. We have determined that glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is present within the secretory granules of islet beta cells. To determine if GPI-PLD is regulated in islet beta cells, we examined the effect of glucose and insulin on GPI-PLD expression in rat islets and murine insulinoma cell lines. Glucose (16.7 mmol/L) increased cellular GPI-PLD activity and mRNA levels 2- to 7-fold in isolated rat islets and betaTC3 and betaTC6-F7 cells. Insulin (10(-7) mol/L) also increased GPI-PLD mRNA levels in rat islets and betaTC6-F7 cells 2- to 4-fold commensurate with an increase in GPI-PLD biosynthesis. To determine if islet GPI-PLD expression is increased in vivo under conditions of islet hyperactivity, we compared GPI-PLD mRNA levels in islets and liver from ob/ob mice and their lean littermates. Islet GPI-PLD mRNA was increased 5-fold while liver mRNA and serum GPI-PLD levels were reduced 30% in ob/ob mice compared with lean littermate controls. These results suggest that glucose and insulin regulate GPI-PLD mRNA levels in isolated islets and beta-cell lines. These regulators may also account for the increased expression of GPI-PLD mRNA in islets from ob/ob mice, a model of insulin resistance and islet hyperactivity.
Bowen
R F
RF
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202-2883, USA.
Raikwar
N S
NS
Olson
L K
LK
Deeg
M A
MA
D000818:Animals; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007340:Insulinoma; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000201:enzymology; D010190:Pancreatic Neoplasms; D010739:Phospholipase D / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D007328:Insulin; D012333:RNA, Messenger; D010739:Phospholipase D; C065017:glycoprotein phospholipase D; D005947:Glucose