Insulinomimetic Properties of Trace Elements and Characterization of Their In Vivo Mode of Action
Insulinomimetic Properties of Trace Elements and Characterization of Their In Vivo Mode of Action
复制标题
微量元素的拟胰岛素特性及其体内作用模式的表征
作者：
L. Rossetti;A. Giaccari;E. Klein;Leslie R. Vogel
锂和钒酸盐在体外具有拟胰岛素作用。在这项研究中，我们研究了锂和钒酸盐对糖尿病（90%部分胰腺切除术）大鼠葡萄糖代谢的体内影响。研究了四组慢性插管大鼠：对照组、糖尿病组、用锂（血浆浓度1.0 ± 0.1 meq/L）和钒酸盐（饮用水中0.05 mg/ml）治疗的糖尿病组以及用锂、钒酸盐、锌和镁治疗的糖尿病组。糖尿病大鼠与对照大鼠相比，餐后血糖升高（18.7对7.7 mM，P <0.01），并通过添加锂和钒酸盐（8 mM）或锂、钒酸盐、锌和镁（7.4 mM）进行标准化。治疗后2wk进行正常血糖胰岛素钳夹试验;与对照组相比，糖尿病大鼠胰岛素介导的葡萄糖摄取减少（142 ± 4 vs. 200 ± 5 μ mol·kg − 1·min − 1，P <0.01），锂和钒酸盐治疗后恢复正常（206 ± 6 μ mol·kg − 1·min − 1），或使用锂、钒酸盐、锌和镁后升高至超正常水平（238 ± 6 μ mol·kg − 1·min − 1）。在胰岛素钳夹过程中，糖尿病大鼠与对照大鼠相比，肌肉糖原生成率严重受损（18 μ mol·kg − 1·min − 1 vs. 70 μ mol·kg − 1·min − 1），并通过锂和钒酸盐（91 μ mol·kg − 1·min − 1）或锂、钒酸盐、锌和镁（93 μ mol·kg − 1·min − 1）恢复正常。全身糖酵解速率在对照组中，[3H]葡萄糖转化为3H2O占葡萄糖处置量的55（106 ± 5 μ mol·kg-1·min-1），糖尿病患者72%（103 ± 3 μ mol·kg − 1·min − 1），锂和钒酸盐治疗的糖尿病患者中为49%（98 ± 4 μ mol·kg-1·min-1），锂、钒酸盐、锌和镁治疗的糖尿病大鼠（132 ± 4 μ mol·kg-1 ± min-1）为56%。我们的结论是，在糖尿病大鼠中，1）胰岛素介导的葡萄糖处理明显受损，这主要反映了肌糖原合成的缺陷，而糖酵解通量没有减少; 2）锂和钒酸盐联合治疗使胰岛素敏感性和肌糖原合成正常化; 3）锌和镁的添加进一步改善葡萄糖处理，主要是通过刺激糖酵解。这些结果表明，微量元素治疗，无论是单独或联合，可能证明在治疗非胰岛素依赖型糖尿病的人有效。
Lithium and vanadate have insulinomimetic actions in vitro. In this study, we examined the in vivo effects of lithium and vanadate on glucose metabolism in diabetic (90% partial pancreatectomy) rats. Four groups of chronically catheterized rats were studied: control, diabetic, diabetic treated with lithium (plasma concn 1.0 ± 0.1 meq/L) and vanadate (0.05 mg/ml in drinking water), and diabetic treated with lithium, vanadate, zinc, and magnesium. Postmeal plasma glucose was increased in diabetic versus control rats (18.7 vs. 7.7 mM, P < 0.01) and was normalized by addition of lithium and vanadate (8 mM) or lithium, vanadate, zinc, and magnesium (7.4 mM). Euglycemic insulin-clamp studies were performed 2 wk posttreatment; insulin-mediated glucose uptake was reduced in diabetic compared with control rats (142 ± 4 vs. 200 ± 5 μmol · kg−1 · min−1 P < 0.01), returned to normal with lithium and vanadate (206 ± 6 μmol · kg−1 · min−1), or increased to supranormal levels with lithium, vanadate, zinc, and magnesium (238 ± 6 μmol · kg−1 · min−1). During the insulin clamp, muscle glycogenic rate was severely impaired in diabetic versus control rats (18 vs. 70 μmol · kg−1 · min−1) and was normalized by lithium and vanadate (91 μmol · kg−1 · min−1) or lithium, vanadate, zinc, and magnesium (93 μmol · kg−1 · min−1). Whole-body glycolytic rate (conversion of [3H]glucose to 3H2O) accounted for 55% of glucose disposal in control (106 ± 5 μmol · kg−1 · min−1), 72% in diabetic (103 ± 3 μmol · kg−1 · min−1), 49% in lithium- and vanadatetreated diabetic (98 ± 4 μmol · kg−1 · min−1), and 56% in lithium-, vanadate-, zinc-, and magnesium-treated diabetic (132 ± 4 μmol · kg−1 ± min−1) rats. We conclude that, in diabetic rats, 1) insulin-mediated glucose disposal is markedly impaired, and this primarily reflects a defect in muscle glycogen synthesis, whereas glycolytic flux is not decreased; 2) combined lithium and vanadate treatment normalizes insulin sensitivity and muscle glycogen synthesis; 3) the addition of zinc and magnesium further improves glucose disposal, primarily by stimulating glycolysis. These results suggest that trace-element therapy, either alone or in combination, may prove effective in the treatment of non-insulin-dependent diabetes in humans.
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DOI：
10.1042/bj2380663
发表时间：
1986
期刊：
The Biochemical journal
影响因子：
--
作者：
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DOI：
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发表时间：
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期刊：
The Journal of nutrition
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1093/ajcn/37.3.382
发表时间：
1983
期刊：
The American journal of clinical nutrition
影响因子：
--
作者：
Levine,AS;McClain,CJ;Handwerger,BS;Brown,DM;Morley,JE
通讯作者：
Morley,JE