Bowen R F, Raikwar N S, Olson L K, Deeg M A
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202-2883, USA.
Metabolism. 2001 Dec;50(12):1489-92. doi: 10.1053/meta.2001.28087.
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.
胰岛素抵抗与胰岛代偿性功能亢进相关，以维持足够的胰岛素生物合成和分泌，从而维持血糖接近正常水平。葡萄糖和胰岛素均参与调节胰岛内胰岛素合成和分泌以及胰岛肥大所需的蛋白质。我们已经确定糖基磷脂酰肌醇特异性磷脂酶D（GPI-PLD）存在于胰岛β细胞的分泌颗粒中。为了确定GPI-PLD在胰岛β细胞中是否受到调节，我们研究了葡萄糖和胰岛素对大鼠胰岛和小鼠胰岛素瘤细胞系中GPI-PLD表达的影响。葡萄糖（16.7 mmol/L）可使分离的大鼠胰岛以及betaTC3和betaTC6-F7细胞中的细胞GPI-PLD活性和mRNA水平增加2至7倍。胰岛素（10^(-7) mol/L）也可使大鼠胰岛和betaTC6-F7细胞中的GPI-PLD mRNA水平增加2至4倍，这与GPI-PLD生物合成的增加相一致。为了确定在胰岛功能亢进的情况下体内胰岛GPI-PLD表达是否增加，我们比较了ob/ob小鼠及其瘦同窝小鼠的胰岛和肝脏中的GPI-PLD mRNA水平。与瘦同窝对照相比，ob/ob小鼠的胰岛GPI-PLD mRNA增加了5倍，而肝脏mRNA和血清GPI-PLD水平降低了30%。这些结果表明，葡萄糖和胰岛素可调节分离的胰岛和β细胞系中的GPI-PLD mRNA水平。这些调节因子也可能解释了ob/ob小鼠（一种胰岛素抵抗和胰岛功能亢进模型）胰岛中GPI-PLD mRNA表达的增加。
