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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)

 
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