ABSTRACT

Aurora-A kinase, a serine/threonine mitotic kinase, is reportedly upregulated in skin tissues of individuals with type 2 diabetes mellitus , although its function in diabetes is unclear. C57BL/6 J mice were utilized to establish a type 2 diabetic model and explore the functions of Aurora-A in diabetes. Aurora-A was highly expressed in the pancreas of the diabetic mice as confirmed by western blot. Inhibition of Aurora-A did not affect fasting blood glucose and body weight, but did improve insulin resistance, as indicated by improved oral glucose tolerance, insulin tolerance, and the Homoeostasis Model Assessment-Insulin Resistance index. Blockade of Aurora-A dramatically decreased the number of infiltrating macrophages in the pancreas in parallel with decreases in the levels of serum insulin and interleukin-6 (IL-6) mRNA. The levels of phosphorylated forms of protein kinase B, which are the key mediators of in insulin resistance, were not induced in liver, adipocyte tissues, and skeletal muscle by alisertib treatment. Our findings indicate that suppression of Aurora-A could at least partially enhance insulin sensitivity by decreasing the number of infiltrating macrophages and IL-6 level in a type 2 diabetic mouse model.

摘要

据报道，Aurora-A激酶（一种丝氨酸/苏氨酸有丝分裂激酶）在2型糖尿病患者的皮肤组织中上调，尽管尚不清楚其在糖尿病中的功能。使用C57BL / 6 J小鼠建立2型糖尿病模型并探索Aurora-A在糖尿病中的功能。Western blot证实，Aurora-A在糖尿病小鼠的胰腺中高表达。抑制Aurora-A不会影响空腹血糖和体重，但确实改善了胰岛素抵抗，如口服葡萄糖耐量，胰岛素耐受性和同流模型评估-胰岛素抵抗指数的改善所表明。阻断Aurora-A可以显着减少胰腺中浸润性巨噬细胞的数量，同时降低血清胰岛素和白介素6（IL-6）mRNA的水平。蛋白激酶B的磷酸化形式是胰岛素抵抗的关键介体，但通过alisertib处理未在肝脏，脂肪细胞组织和骨骼肌中诱导磷酸化形式的水平。我们的发现表明，在2型糖尿病小鼠模型中，通过减少浸润性巨噬细胞的数量和IL-6水平，抑制Aurora-A可以至少部分增强胰岛素敏感性。