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 eugly cemia. Both glucose and insulin are involved in regulating proteins require d for insulin synthesis and secretion within the islet and islet hypertroph y. We have determined that glycosylphosphatidylinositol-specific phospholip ase D (GPI-PLD) is present within the secretory granules of islet beta cell s. To determine if GPI-PLD is regulated in islet beta cells, we examined th e effect of glucose and insulin on GPI-PLD expression in rat islets and mur ine 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 beta TC3 and beta TC6-F7 cells. Insulin (10(-7) mol/L) also increased GPI-PLD mRNA l evels in rat islets and beta TC6-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 litt ermates. 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 littermat e 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. Copyright (C) 2001 by W.B. Saunders Company.