BACKGROUND Macrophages (MPhis) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized by metabolic abnormalities and altered immune function. Here we examine the influence of diabetes on macropinocytosis in primary mouse macrophages and in an in vitro diabetes model. RESULTS The data demonstrate that peritoneal MPhis from diabetic (db/db) mice had reduced macropinocytosis when compared to MPhis from non-diabetic (db/+) mice. Additionally, MPhis cultured in hyperglycemic conditions were less adept at macropinocytosis than those cultured in low glucose. Notably, AMP-activated protein kinase (AMPK) activity was decreased in MPhis cultured in hyperglycemic conditions. Activation of AMPK with leptin or 5-aminoimidazole-4-carboxamide-1-beta-riboside (AICAR) increased macropinocytosis and inhibition of AMPK with compound C decreased macropinocytosis. CONCLUSION Taken together, these findings indicate that MPhis from diabetic mice have decreased macropinocytosis. This decrease appears dependent on reduced AMPK activity. These results demonstrate a previously unrealized role for AMPK in MPhis and suggest that increasing AMPK activity in diabetic MPhis could improve innate immunity and decrease susceptibility to infection.

中文翻译：

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糖尿病小鼠巨噬细胞的巨胞饮作用减少，并受 AMPK 调节。

背景巨噬细胞（MPhis）利用巨胞饮作用来整合免疫和代谢信号，以启动有效的免疫反应。糖尿病的特点是代谢异常和免疫功能改变。在这里，我们研究了糖尿病对原代小鼠巨噬细胞和体外糖尿病模型中巨胞饮作用的影响。结果数据表明，与非糖尿病 (db/+) 小鼠的 MPhi 相比，糖尿病 (db/db) 小鼠的腹膜 MPhi 的巨胞饮作用减少。此外，在高血糖条件下培养的 MPhi 比在低血糖条件下培养的 MPhi 不太擅长巨胞饮作用。值得注意的是，在高血糖条件下培养的 MPhis 中 AMP 激活蛋白激酶 (AMPK) 活性降低。用瘦素或 5-氨基咪唑-4-甲酰胺-1-β-核苷 (AICAR) 激活 AMPK 会增加巨胞饮作用，而用化合物 C 抑制 AMPK 会减少巨胞饮作用。结论 综上所述，这些发现表明糖尿病小鼠的 MPhi 巨胞饮作用降低。这种减少似乎取决于 AMPK 活性的减少。这些结果证明了 AMPK 在 MPhis 中以前未实现的作用，并表明增加糖尿病性 MPhis 中的 AMPK 活性可以改善先天免疫并降低对感染的易感性。