Shin Jun-Seop, Torres Tracy P, Catlin Reetta L, Donahue E P, Shiota Masakazu
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall, Nashville, TN 37232-0615, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1381-90. doi: 10.1152/ajpregu.00260.2006. Epub 2007 Jan 4.
Effect of stimulation of glucokinase (GK) export from the nucleus by small amounts of sorbitol on hepatic glucose flux in response to elevated plasma glucose was examined in 6-h fasted Zucker diabetic fatty rats at 10 wk of age. Under basal conditions, plasma glucose, insulin, and glucagon were approximately 8 mM, 2,000 pmol/l, and 60 ng/l, respectively. Endogenous glucose production (EGP) was 44 +/- 4 micromol x kg(-1) x min(-1). When plasma glucose was raised to approximately 17 mM, GK was still predominantly localized with its inhibitory protein in the nucleus. EGP was not suppressed. When sorbitol was infused at 5.6 and 16.7 micromol x kg(-1) x min(-1), along with the increase in plasma glucose, GK was exported to the cytoplasm. EGP (23 +/- 19 and 12 +/- 5 micromol x kg(-1) x min(-1)) was suppressed without a decrease in glucose 6-phosphatase flux (145 +/- 23 and 126 +/- 16 vs. 122 +/- 10 micromol x kg(-1) x min(-1) without sorbitol) but increased in glucose phosphorylation as indicated by increases in glucose recycling (122 +/- 17 and 114 +/- 19 vs. 71 +/- 11 microl x kg(-1) x min(-1)), glucose-6-phosphate content (254 +/- 32 and 260 +/- 35 vs. 188 +/- 20 nmol/g liver), fractional contribution of plasma glucose to uridine 5'-diphosphate-glucose flux (43 +/- 8 and 42 +/- 8 vs. 27 +/- 6%), and glycogen synthesis from plasma glucose (20 +/- 4 and 22 +/- 5 vs. 9 +/- 4 mumol glucose/g liver). The decreased glucose effectiveness to suppress EGP and stimulate hepatic glucose uptake may result from failure of the sugar to activate GK by stimulating the translocation of the enzyme.
在10周龄的禁食6小时的Zucker糖尿病脂肪大鼠中，研究了少量山梨醇刺激葡萄糖激酶（GK）从细胞核输出对血浆葡萄糖升高时肝脏葡萄糖通量的影响。在基础条件下，血浆葡萄糖、胰岛素和胰高血糖素分别约为8 mM、2000 pmol/l和60 ng/l。内源性葡萄糖生成（EGP）为44±4 μmol·kg⁻¹·min⁻¹。当血浆葡萄糖升高至约17 mM时，GK仍主要与其抑制蛋白一起定位于细胞核中。EGP未被抑制。当以5.6和16.7 μmol·kg⁻¹·min⁻¹的速率输注山梨醇时，随着血浆葡萄糖的升高，GK被输出到细胞质中。EGP（23±19和12±5 μmol·kg⁻¹·min⁻¹）被抑制，而葡萄糖6-磷酸酶通量没有降低（分别为145±23和126±16，而无山梨醇时为122±10 μmol·kg⁻¹·min⁻¹），但葡萄糖磷酸化增加，表现为葡萄糖再循环增加（分别为122±17和114±19，而无山梨醇时为71±11 μl·kg⁻¹·min⁻¹）、葡萄糖-6-磷酸含量增加（分别为254±32和260±35，而无山梨醇时为188±20 nmol/g肝脏）、血浆葡萄糖对尿苷5'-二磷酸葡萄糖通量的分数贡献增加（分别为43±8和42±8，而无山梨醇时为27±6%）以及血浆葡萄糖合成糖原增加（分别为20±4和22±5，而无山梨醇时为9±4 μmol葡萄糖/g肝脏）。葡萄糖抑制EGP和刺激肝脏葡萄糖摄取的有效性降低可能是由于该糖类未能通过刺激该酶的易位来激活GK所致。
