Hyperglycaemia causes pancreatic β-cells to release insulin that then attaches to a specific expression of receptor isoform and reverses high glucose concentrations. It is well known that insulin is capable of initiating insulin-receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling pathways in target cells; such as liver, adipose tissues, and muscles. However, recent discoveries indicate that many other pathways, such as the Hedgehog (Hh) and growth factor-stimulating Wingless-related integration (Wnt) signaling pathways; are activated in hyperglycaemia as well. Although these two pathways are traditionally thought to have a decisive role in cellular growth and differentiation only, recent reports show that they are involved in regulating cellular homeostasis and energy balance. While insulin-activated IRS/PI3K/PKB pathway cascades are primarily known to reduce glucose production, it was recently discovered to increase the Hh signaling pathway's stability, thereby activating the PI3K/PKB/mammalian target of rapamycin complex 2 (mTORC2) signaling pathway. The Hh signaling pathway not only plays a role in lipid metabolism, insulin sensitivity, inflammatory response, diabetes-related complications, but crosstalks with the Wnt signaling pathway resulting in improved insulin sensitivity and decrease inflammatory response in diabetes.

高血糖症会导致胰腺β细胞释放胰岛素，然后胰岛素会与受体同种型的特定表达结合并逆转高血糖浓度。众所周知，胰岛素能够在靶细胞中启动胰岛素受体底物（IRS）/磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（PKB）信号传导途径。例如肝脏，脂肪组织和肌肉。但是，最近的发现表明，还有许多其他途径，例如刺猬（Hh）和刺激生长因子的Wingless相关整合（Wnt）信号传导途径。在高血糖症中也被激活。尽管传统上认为这两种途径仅在细胞生长和分化中起决定性作用，但最近的报道表明它们参与调节细胞稳态和能量平衡。虽然最初已知胰岛素激活的IRS / PI3K / PKB途径级联会降低葡萄糖生成，但最近发现它可以增加Hh信号传导途径的稳定性，从而激活雷帕霉素复合物2（mTORC2）信号传导途径的PI3K / PKB /哺乳动物靶标。Hh信号通路不仅在脂质代谢，胰岛素敏感性，炎症反应，糖尿病相关并发症中起作用，而且与Wnt信号通路的串扰导致胰岛素敏感性提高，并降低了糖尿病的炎症反应。