MiR-15b can target insulin receptor to regulate hepatic insulin signaling in mice

Yan-Shu Lian,Jin-Rong Xia,Wei-Dong Li

doi:10.1080/19768354.2019.1583125

Abstract

ABSTRACTNow diabetes is growing to be a health problems globally. However, its specific pathogenesis still needs further exploration. Here we showed that miR-15b was upregulated in the palmitate-induced HepG2 cells and livers of hyperglycemic mice. At the same time, we confirmed that the insulin receptor was a direct target of miR-15b. Then we found that the manipulation of miR-15b expression level could affect the insulin signaling pathway of HepG2 cells and the inhibition of miR-15b in liver of ob/ob mice can improve insulin sensitivity of mice. Furthermore, our study demonstrated that palmitate could upregulate the expression of miR-15b by activating PPARα. Our findings established PPARα-responsive miR-15b as a critical regulator of hepatic insulin signaling, thus serving as a new potential therapeutic target for diabetes.

Highlights

Diabetes is a rapidly growing global health problem that is closely related to the pathogenesis of metabolic syndrome (Boren et al 2013)
We found palmitate caused a decrease in IR protein level in HepG2 cells
We further examined the expression level of miR15b in liver, epididymal visceral adipose (EP) and muscle in High fat diet (HFD) and ob/ob mice, and we found miR-15b expression was significantly increased in the liver of HFD and ob/ob mice, but not in EP and muscle (Figure 1(c–d))

Summary

Introduction

Diabetes is a rapidly growing global health problem that is closely related to the pathogenesis of metabolic syndrome (Boren et al 2013). Type 2 diabetes is characterized by hyperglycemia and decreased response of peripheral tissues to insulin (Kahn et al 2006; Petersen and Shulman 2006). Hepatic insulin resistance is one of the most important causes for the development of type 2 diabetes. In the state of insulin resistance, the liver’s response to insulin is reduced, while gluconeogenesis is increased and glycogen synthesis is reduced simultaneously, eventually leading to hyperglycemia in the body (Samuel and Shulman 2012). Studies on the complex network of liver insulin signaling pathway can help us to understand the molecular mechanism of hepatic insulin resistance and type 2 diabetes and provide new solutions for the treatment of metabolic diseases. Liver-specific knockout IR mice show hyperglycemia, hyperlipidemia, hyperinsulinemia and obesity (Michael et al 2000).

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Results

Conclusion