Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and AKT in 3T3-L1 fibroblasts and adipocytes
Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and AKT in 3T3-L1 fibroblasts and adipocytes
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DOI：
10.1093/jn/131.5.1414
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发表时间：
2001-05-01
影响因子：
4.2
通讯作者：
Shay, NF
中科院分区：
文献类型：
--
作者：
Tang, XH;Shay, NF
锌对细胞具有胰岛素样作用，包括促进脂肪生成和葡萄糖转运。锌和葡萄糖转运刺激之间的关系尚不清楚。我们假设锌影响胰岛素信号通路。在这项研究中，锌对葡萄糖转运和胰岛素信号转导的影响进行了研究，在3 T3-L1 -前脂肪细胞和-脂肪细胞。200 μ mol/L的锌处理显著增加了细胞的葡萄糖转运（P < 0.05）。锌对脂肪细胞的作用大于对前脂肪细胞的作用，锌加胰岛素的作用大于胰岛素或单独锌的作用。细胞松弛素D破坏肌动蛋白丝，减弱锌或胰岛素诱导的葡萄糖转运增加（P < 0.05）。在100 nmol/L时，磷脂酰肌醇（PI）3-激酶抑制剂wortmannin可降低两种细胞的基础葡萄糖转运，并阻断锌刺激的葡萄糖转运（P < 0.05）。蛋白激酶C抑制剂H7不降低基础葡萄糖转运，但降低锌诱导的葡萄糖转运（P < 0.05）。锌处理5-10 min后，前脂肪细胞和脂肪细胞胰岛素受体β亚基酪氨酸磷酸化水平均升高（P < 0.05）。200 μ mol/L锌对胰岛素受体底物（IRS）-1或-2的酪氨酸磷酸化无影响，对PI 3-激酶p85亚基与IRS-1的结合无影响，锌显著增加前脂肪细胞和脂肪细胞Akt的丝氨酸-473磷酸化（P < 0.05）。PI 3激酶抑制剂wortmannin可完全阻断锌对Akt激活的影响。因此，锌似乎可以诱导葡萄糖转运到细胞中的增加，并增强胰岛素诱导的葡萄糖转运，可能通过胰岛素信号通路起作用。
Zinc has insulin-like effects on cells, including promotion of both lipogenesis and glucose transport. The relationship between zinc and the stimulation of glucose transport is unclear. We hypothesize that zinc affects the insulin-signaling pathway. In this study, the effect of zinc on glucose transport and insulin signaling was examined in 3T3-L1 -preadipocytes and -adipocytes. Treatment of cells with up to 200 mu mol/L zinc significantly increased glucose transport (P < 0.05), The effect of zinc on adipocytes was greater than on preadipocytes, and the effect of zinc plus insulin was greater than that of either insulin or zinc alone. Cytochalasin D, which disrupts actin filaments, attenuated the increase of glucose transport induced by zinc or insulin (P < 0.05). At 100 nmol/L, wortmannin, the phosphoinositide (PI) 3-kinase inhibitor, decreased basal glucose transport and blocked zinc-stimulated glucose transport in both cell types (P < 0.05). H7, an inhibitor of protein kinase C, did not reduce basal glucose transport but decreased zinc-induced glucose transport (P < 0.05), Zinc increased tyrosine phosphorylation of the insulin receptor p subunit of both preadipocytes and adipocytes after 5-10 min of treatment (P < 0.05). Zinc at 200 mu mol/L did not affect tyrosine phosphorylation of insulin receptor substrate (IRS)-1 or -2; further, there was no effect of zinc on the association of the p85 subunit of PI 3-kinase and IRS-1, Zinc significantly increased serine-473 phosphorylation of Akt in both preadipocytes and adipocytes (P < 0.05). The PI 3-kinase inhibitor, wortmannin, totally blocked the effect of zinc on Akt activation. Hence, it appears that zinc can induce an increase in glucose transport into cells and potentiate insulin-induced glucose transport, likely acting through the insulin-signaling pathway.