Chronic intraperitoneal insulin delivery, as compared with subcutaneous delivery, improves hepatic glucose metabolism in streptozotocin diabetic rats.

Chronic intraperitoneal insulin delivery, as compared with subcutaneous delivery, improves hepatic glucose metabolism in streptozotocin diabetic rats.
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与皮下递送相比,慢性腹膜内胰岛素递送可改善链脲佐菌素糖尿病大鼠的肝脏葡萄糖代谢。

DOI:
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发表时间:
2000
期刊:
Metabolism: Clinical and Experimental
影响因子:
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通讯作者:
A. Giacca
A. Giacca
中科院分区:
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文献类型:
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作者:
T. Mason;N. Gupta;T. Goh;B. El;J. Zannis;G. Werve;A. Giacca

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我们以前已经表明,腹膜内途径的慢性胰岛素治疗使链脲佐菌素(STZ)糖尿病大鼠的葡萄糖产生(GP)升高正常化,而皮下途径的胰岛素仅使GP部分正常化。为了探讨通过两种途径长期输送胰岛素对肝脏葡萄糖代谢影响的生化机制,我们测量了葡萄糖6-磷酸酶(G6 Pase)和葡萄糖激酶(GK)的肝脏活性。使用四组大鼠:(1)非糖尿病大鼠(N,n = 7),(2)未治疗的STZ糖尿病大鼠(D,n = 8),(3)腹膜内(IP,n = 6)或(4)皮下(SC,n = 8)治疗的糖尿病大鼠(均为3U胰岛素/d)。葡萄糖水平,更高的D,正常的胰岛素治疗,无论途径。外周胰岛素水平在D组最低,在SC组最高,与预期一致(N,162 +/- 18 pmol/L; D,66 +/- 12; IP,360 +/- 96; SC,798 +/- 198)。STZ糖尿病导致GK降低10倍(P <0.001),G6 β活性增加2倍(P <0.01)。腹膜内和皮下处理均使G6 β活性正常化。相比之下,皮下注射而非腹腔注射治疗,GK活性仍比正常低35%(SC vs N,P <0.05)。葡萄糖6-磷酸(G6 P)水平在各组之间没有差异。总结如下:(1)D组GP增加反映了G6 β活性增加和GK活性降低,(2)皮下胰岛素治疗对GP的部分抑制反映了G6 β活性增加的纠正,但仅部分纠正了低GK活性,(3)腹腔胰岛素治疗对GP的正常化反映了G6 β活性增加和低GK活性的纠正。我们目前的研究表明,长期腹腔注射胰岛素治疗在肝脏葡萄糖代谢方面上级皮下注射胰岛素治疗。
We have previously shown that chronic insulin treatment by the intraperitoneal route normalizes the elevated glucose production (GP) in streptozotocin (STZ) diabetic rats, while insulin delivered by the subcutaneous route only partially normalizes GP. To investigate the biochemical mechanism of the effect of chronic insulin delivery by either route on hepatic glucose metabolism, we measured the hepatic activity of glucose 6-phosphatase (G6Pase) and glucokinase (GK). Four groups of rats were used: (1) nondiabetic rats (N, n = 7), (2) untreated STZ diabetic rats (D, n = 8), (3) diabetic rats treated intraperitoneally (IP, n = 6), or (4) subcutaneously (SC, n = 8) (both 3 U of insulin/d). Glucose levels, higher in D, were normalized by insulin treatment regardless of route. Peripheral insulin levels were lowest in D and highest in SC as expected (N, 162 +/- 18 pmol/L; D, 66 +/- 12; IP, 360 +/- 96; SC, 798 +/- 198). STZ diabetes resulted in a 10-fold decrease in GK (P < .001), and a 2-fold increase in G6Pase activity (P < .01). Both intraperitoneal and subcutaneous treatments normalized G6Pase activity. In contrast, with subcutaneous but not intraperitoneal treatment, GK activity was still 35% less than normal (SC v N, P < .05). Glucose 6-phosphate (G6P) levels did not differ among the groups. In summary: (1) the increase in GP in D reflected increased activity of G6Pase and reduced activity of GK, (2) the partial suppression of GP with subcutaneous insulin treatment reflected correction of increased G6Pase activity, but only partial correction of low GK activity, and (3) the normalization of GP with intraperitoneal insulin treatment reflected correction of both increased G6Pase activity and low GK activity. Our current studies indicate that chronic intraperitoneal insulin treatment is superior to subcutaneous treatment with regard to hepatic glucose metabolism.
大鼠肝葡萄糖-6-磷酸酶催化亚基 cDNA 的分离:胰岛素、地塞米松和 cAMP 对FAO 肝癌细胞中基因表达的调节。
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