AMP‐activated protein kinase‐mediated expression of heat shock protein beta 1 enhanced insulin sensitivity in the skeletal muscle

Abstract

Activation of AMP-activated protein kinase (AMPK) has been viewed as an important target for the treatment of insulin resistance. Here, by proteomic analysis, we found that expression of heat shock protein beta-1 (HSPB1) was induced by the AMP analog 5-aminoimidazole-4-carboxamide 1-b-D-ribofuranoside in palmitate-induced insulin-resistant cells. Overexpression of AMPKa2, or activation of AMPKa via acute/chronic exercise training, increased HSPB1 expression in the skeletal muscle. In AMPKa2 À/À mice, HSPB1 expression was downregulated in the quadriceps muscles. Exercise did not increase HSPB1 expression in AMPKa2 À/À mice. Moreover, overexpression of HSPB1 enhanced insulin sensitivity in palmitate-induced insulinresistant cells and restored metabolic phenotypes associated with defective AMPK. Finally, HSPB1 was required for AMPK-mediated activation of the class IIa histone deacetylases and glucose uptake in the skeletal muscle. Our results demonstrate that AMPK-mediated HSPB1 expression enhanced insulin sensitivity in the skeletal muscle.

LRP6 Knockdown Ameliorates Insulin Resistance via Modulation of Autophagy by Regulating GSK3β Signaling in Human LO2 Hepatocytes

“…Expression vectors for recombinant adenovirus were constructed according to the Gateway cloning system (Invitrogen, Carlsbad, CA, USA) as previously described (16). Briefly, Si-LRP6, GFP-LC3, GSK3β were cloned into the pAD/CMB/V5-DEST vector and packaged by ViraPower Adenoviral expression system (Invitrogen, Carlsbad, CA, USA).…”

In vitro experimental models for examining the skeletal muscle cell biology of exercise: the possibilities, challenges and future developments

“…Applications Whilst AICAR is not always specifically used as an 'exercise-like treatment', AICAR has commonly been used as an AMPK activator within the context of exercise physiology. For example, AICAR applied to C2C12 and L6 myotubes to study signalling pathways [8,27,31,56,79,88,111], metabolism [17,51,117], myokine release [114] and protection against palmitate [108,124] that may be regulated by exercise-like AMPK activation. That said, studies have also used AICAR with the stated intention to induce 'exercise signals' [79], to serve as an 'exercise-mimetic precursor' [90,110] and to generate 'trained' cells [94] to study exercise-related signalling [90,91], myokine release [110] and cross-talk [94].…”

“…Similarly, acetyl-CoA carboxylase (ACC) PKA activator 30 min 20 μM [ 76] activation is a common finding across all cell types following AICAR treatment (C2C12, [51,76]; L6, [43,60,98]; human [36]). Other exercise-like changes reported following AICAR treatment include increased GLUT4 protein content [91,107], glucose uptake or oxidation [17,66,77,98,107], fatty acid uptake or oxidation [60,66,82,98], insulin responsiveness [10,124], GLUT4 translocation [43,107], mitochondrial content [22] and IL-6 secretion [110]. However, in contrast to some of these above-described findings, other studies demonstrate a lack of effect of AICAR upon PGC-1α mRNA expression [6,110], pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression [6,64], FNDC5 (gene that encodes for irisin) mRNA expression [110], as well as lack of effect upon protein kinase B (Akt) protein content [56] and activation [31,43], as well as Akt substrate 160 (AS160) activation [31,43].…”

Insulin-dependent and -independent dynamics of insulin receptor trafficking in muscle cells

“…Heat shock protein B1 (HSPB1; a.k.a. HSP27) is exclusively found in insulin-responsive tissues and has been implicated in insulin sensitivity and INSR/IGF1R signalling 28–30 . The PPI network and cellular localization of these interactors pointed to the possibility that INSR may also associate with caveolins and/or related proteins in myoblasts.…”