Akt activation: A potential strategy to ameliorate insulin resistance

作者：Zhang, Zhengyi; Liu, Huadong; Liu, Jiankang^*

来源：Diabetes Research and Clinical Practice, 2019, 156: UNSP 107092.

DOI：10.1016/j.diabres.2017.10.004

• Akt/PKB
• AMPK
• Insulin resistance
• IP6K1
• Type 2 diabetes

Insulin resistance is a hallmark of type 2 diabetes and obesity while the mechanism remains unclear. Current therapy to treat type 2 diabetes is metformin, the 5'-monopho sphate-activated protein kinase (AMPK) activator, owing to the ability to augment peripheral glucose uptake. However, metformin also displays limitations, as AMPK activation remains intact and regular in most type 2 diabetes and metformin does not seem to facilitate peripheral insulin resistance. Evidence has shown that PI3K-Akt/PKB pathway could be induced via insulin and act as an important effector. Akt/PKB is capable of inducing a great number of downstream molecules, such as translocating glucose transporters GLUTs to the cell membrane thus increase glucose uptake. Hence, any defect in Akt/PKB pathway along with the downstream molecules could lead to insulin resistance. Inositol pyrophosphates, synthesized by inositol hexakisphosphate (IP6) kinase 1 (IP6K1) and competitive with 3,4,5-bisphosphate (PIP3) to bind the PH domain of Akt/PKB, demonstrate the ability to inhibit Akt signaling. In addition, IP6K1 knockout mice present increased insulin sensitivity and obesity resistance, indicating a novel therapeutic target in confronting insulin resistance. Taken together, we conclude that Akt activation is another potential strategy to ameliorate insulin resistance.

• 出版日期2019-10
• 单位西安交通大学