1 The abnormality in the signaling pathway, including insulin receptor (IR), insulin receptor substrate (IRS), and their downstream molecules,2 marks the main pathophysiological characteristics of insulin resistance. However, the molecular mechanisms underlying insulin resistance and impairment of insulin signaling network in the liver are not completely understood yet. Protein tyrosine phosphatase (PTP) constitutes a family of phosphatases including PTP1B, SHP1, SHP2, and LAR.3, 4 As a negative Selleck FDA approved Drug Library regulator of insulin signaling cascade,

PTP1B functions as a key phosphatase and reverses tyrosine kinase action.5 A deficiency of PTP1B improved glycemic control by enhancing sensitivity to insulin and made animals more resistant to diet-induced obesity.6 In addition, antisense oligonucleotides

of PTP1B decreased blood glucose content, insulin level, and fat mass in diabetic animals.7 However, the upstream regulators or mediators that control transcription and translation of the PTP1B gene are not well defined. Moreover, pharmacological agents that intervene with PTP1B activity are not available, despite recognition of PTP1B inhibition as an effective way to improve insulin sensitivity.8 The microRNAs (miRNAs) have diverse Ibrutinib functions in normal or pathological states.9 The consequences of changes in miRNA levels can affect not only lipid metabolism, but insulin signaling, potentially influencing glucose homeostasis and the development of diabetes. In fact, dysregulation of miRNA is implicated in defective insulin secretion, diabetic kidney,

and heart diseases.10 Hepatocyte-specific deletion of Dicer, an enzyme essential for miRNA processing, resulted in the depletion of glycogen storage and led to mild hyperglycemia in the fed state and severe hypoglycemia in the fasting state.11 However, the genes targeted by miRNAs and their individual biological functions largely remain to be established. In particular, more information is necessary to understand the involvement find more of miRNAs in insulin resistance and find the pharmacological methods to modulate their levels. DN-JNK1, dominant-negative JNK1; G6Pase, glucose 6-phosphatase; HA-JNK1, HA-tagged JNK1; HFD, high-fat diet; HNF4α, hepatocyte nuclear factor 4α; IR, insulin receptor; IRS, insulin receptor substrate; IsoLQ, isoliquiritigenin; JNK, c-Jun N-terminal kinase; LQ, liquiritigenin; miR-122, microRNA-122; miRNA, microRNA; ND, normal diet; PTP, protein tyrosine phosphatase; TNF-α, tumor necrosis factor-α; 3′UTR, 3′-untranslated region.