四氧嘧啶糖尿病及抗胰岛素血清治疗对泌乳大鼠乳腺葡萄糖代谢途径的影响。

Effect of alloxan-diabetes and treatment with anti-insulin serum on pathways of glucose metabolism in lactating rat mammary gland.

作者信息

Walters E, McLean P

出版信息

Biochem J. 1968 Sep;109(3):407-17. doi: 10.1042/bj1090407.

DOI:10.1042/bj1090407

PMID:5693642

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1186835/

Abstract

The overall metabolic changes in lactating mammary gland in alloxan-diabetic and anti-insulin-serum-treated rats were assessed by measurement of the incorporation of (14)C from specifically labelled glucose, pyruvate and acetate into carbon dioxide and lipid, together with measurements of enzymes concerned with the pentose phosphate pathway and with citrate metabolism. 2. Alloxan-diabetes depressed the rate of formation of (14)CO(2) from [1-(14)C]glucose and [2-(14)C]glucose to approx. 10% of the control rate; this was partially reversed by addition of insulin in vitro. The quotient Oxidation of [1-(14)C]glucose/Oxidation of [6-(14)C]glucose fell from a value of 17.6 in the control group to 3.9 in the diabetic group and was restored to 14.3 in the presence of insulin in vitro. In keeping with these results it was shown that glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were significantly decreased in alloxan-diabetic rats. 3. Alloxan-diabetes depressed the decarboxylation and the oxidation of labelled pyruvate, but not the oxidation of labelled acetate. 4. The synthesis of lipid from specifically labelled glucose was greatly decreased, that from [2-(14)C]pyruvate was almost unchanged and that from [1-(14)C]acetate alone was increased in alloxandiabetic rats. However, the stimulation of lipid synthesis from acetate by glucose was small in the alloxan-diabetic rats compared with the controls. Insulin in vitro partially reversed all these effects. Both citrate-cleavage enzyme and acetate thiokinase activities were decreased in alloxan-diabetic rats. 5. Treatment of rats with anti-insulin serum depressed the formation of (14)CO(2) from [1-(14)C]glucose and [2-(14)C]glucose, but increased that from [6-(14)C]glucose. This was completely restored by the presence of insulin in vitro. The quotient Oxidation of [1-(14)C]glucose/Oxidation of [6-(14)C]glucose fell from a value of 17.6 in the control group to 3.8 in the anti-insulin-serum-treated group. There were no changes in the activity of glucose 6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase, but the hexokinase distribution changed and the content of the soluble fraction increased significantly. 6. The synthesis of lipid from specifically labelled glucose was depressed in anti-insulin-serum-treated rats; this effect was completely reversed by addition of insulin in vitro to the tissue slices.

摘要

通过测量特定标记的葡萄糖、丙酮酸和乙酸盐中的（14）C掺入二氧化碳和脂质中的情况，以及与磷酸戊糖途径和柠檬酸代谢相关的酶的活性，评估了用四氧嘧啶诱导糖尿病和抗胰岛素血清处理的大鼠乳腺中的整体代谢变化。2. 四氧嘧啶糖尿病使[1-（14）C]葡萄糖和[2-（14）C]葡萄糖生成（14）CO2的速率降至对照组速率的约10%；在体外添加胰岛素可部分逆转这种情况。[1-（14）C]葡萄糖氧化/[6-（14）C]葡萄糖氧化的商值从对照组的17.6降至糖尿病组的3.9，并在体外存在胰岛素的情况下恢复至14.3。与这些结果一致的是，四氧嘧啶糖尿病大鼠中的葡萄糖6-磷酸脱氢酶和6-磷酸葡萄糖酸脱氢酶活性显著降低。3. 四氧嘧啶糖尿病抑制了标记丙酮酸的脱羧和氧化，但不影响标记乙酸盐的氧化。4. 四氧嘧啶糖尿病大鼠中，由特定标记葡萄糖合成脂质的量大幅减少，由[2-（14）C]丙酮酸合成脂质的量几乎不变，仅由[1-（14）C]乙酸盐合成脂质的量增加。然而，与对照组相比，四氧嘧啶糖尿病大鼠中葡萄糖对乙酸盐合成脂质的刺激作用较小。体外添加胰岛素可部分逆转所有这些影响。四氧嘧啶糖尿病大鼠中的柠檬酸裂解酶和乙酸硫激酶活性均降低。5. 用抗胰岛素血清处理大鼠会抑制[1-（14）C]葡萄糖和[2-（14）C]葡萄糖生成（14）CO2，但会增加[6-（14）C]葡萄糖生成（14）CO2的量。在体外存在胰岛素的情况下，这种情况可完全恢复。[1-（14）C]葡萄糖氧化/[6-（14）C]葡萄糖氧化的商值从对照组的17.6降至抗胰岛素血清处理组的3.8。葡萄糖6-磷酸脱氢酶或6-磷酸葡萄糖酸脱氢酶的活性没有变化，但己糖激酶的分布发生了变化，可溶性部分的含量显著增加。6. 用抗胰岛素血清处理的大鼠中，由特定标记葡萄糖合成脂质的量减少；在体外向组织切片中添加胰岛素可完全逆转这种作用。