Muscle
Insulin resistance also affects the skeletal muscle in diabetes, and some miRNAs are thought to be differentially expressed in this context. MiR-29a and miR-29b levels are upregulated in the skeletal muscle of GK rats compared to their healthy counterparts (He et al. 2007). Moreover, miR-1 and miR-133 have been shown to respond to insulin, but their regulation in the skeletal muscle of T2DM patients is impaired, which may possibly adversely affect muscle function (Granjon et al. 2009).
Liver
miR-29a, miR-29b, miR-103 and miR-107 expression is increased in diabetic adipose tissue, as previously stated, but they are also upregulated in in the liver of diabetic rats, suggesting a more generalized role in insulin resistance (Trajkovski et al. 2011; Herrera et al. 2010). Another miRNA involved in insulin resistance in the liver is miR-181a. Expression is increased in insulin-resistant cultured hepatocytes, as well as in the liver and in the serum of diabetic patients, and it causes insulin resistance by inhibiting SIRT1 (Zhou et al. 2012), which itself is known to improve insulin sensitivity (Stefanowicz et al. 2015). MiR-130a-3p increases insulin sensitivity in hepatocytes. Levels are decreased in the livers of db/db mice, but forced overexpression in this model improved liver steatosis (Xiao et al. 2014).
Taking together, these data suggest that miRNAs may participate in the onset and development of diabetes, having an influence on insulin production, secretion and action and in glucose homeostasis. More information can be found in other reviews (Shantikumar et al. 2012; Chakraborty et al. 2014; Ozcan 2014; Beltrami et al. 2014). A summary of the miRNAs involved in insulin resistance is found in Table 3.2 (Lustig et al. 2014; Najafi-Shoushtari et al. 2010; Ryu et al. 2011; Shi et al. 2007, 2014).
Table 3.2 MicroRNAs involved in insulin resistance
microRNA |
Change in diabetes |
Target(s) |
Functional result |
Reference |
miR-33a/b |
Up |
IRS2 |
Decreased intracellular insulin signalling |
Najafi-Shoushtari et al. (2010) |
miR-103 |
Up |
Caveolin 1 |
Increases adipogenesis |
Trajkovski et al. (2011) |
miR-107 |
Up |
Caveolin 1 |
Increases adipogenesis |
Trajkovski et al. (2011) |
miR-126 |
Up |
IRS1 |
Decreased intracellular insulin signalling |
Ryu et al. (2011) |
miR-143 |
Down |
ERK5 |
Increases adipogenesis |
Esau et al. (2004) |
miR-145 |
Up |
IRS1 |
Decreased intracellular insulin signalling |
Shi et al. (2007) |
miR-181a |
Up |
SIRT1 |
Increases insulin resistance |
Zhou et al. (2012) |
miR-221 |
Up |
AdipoR1 |
Decreases adiponectin signalling |
Lustig et al. (2014) |
miR-222 |
Up |
ERa |
Increases insulin resistance in gestational diabetes |
Shi et al. (2014) |