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.