Asprosin promotes β‐cell apoptosis by inhibiting the autophagy of β‐cell via AMPK‐mTOR pathway

Abstract

Asprosin is a newly discovered adipokine. A recent study showed that asprosin promoted the β-cell apoptosis of MIN6 cells. This study aims to determine whether asprosin induces the apoptosis in β-cell via regulating autophagy. Mouse insulinoma MIN6 cells were divided into the following four groups: control, vehicle, high glucose, and asprosin groups. MIN6 cells in the asprosin group were transfected with recombinant asprosin-T2A-GFP vector. MIN6 cells in the vehicle group were transfected with vector only. Then the apoptosis of MIN6 cells was detected using flow cytometry. Real-time polymerase chain reaction and western blot were used to determine the expression of caspase 3, LC3-I, LC3-II, beclin 1, P62, AMP activated protein kinase (AMPK), and mammalian target of rapamycin (mTOR). AMPK pathway was enhanced using AMPK agonist AICAR. High glucose and asprosin induced the apoptosis of MIN6 cells and elevated expression of caspase 3. In addition, high glucose and asprosin resulted in reduced expression of LC3-II/LC3-I, beclin 1, and increased expression of P62. p-AMPK expression was decreased and p-mTOR expression was increased after high glucose and asprosin treatment. AMPK agonist AICAR was used to activate the AMPK pathway. Treatment with AICAR significantly partly restored decreased autophagy and increased apoptosis of β-cell, which was induced by asprosin. Asprosin promotes the apoptosis of β-cell by inhibiting the autophagy of β-cell via AMPK-mTOR pathway.

Serum levels of Asprosin in patients diagnosed with coronary artery disease (CAD): a case-control study

“…Lee et al found that, under hyperlipidemic conditions, pancreatic β-cells release asprosin, elucidating inflammation, cellular dysfunction and apoptosis via toll-like receptor-4 (TLR-4) / c-Jun N-terminal kinase (JNK) phosphorylation, that eventually leading to insulin resistance [ 14 ]. Recently, Wang et al demonstrated that asprosin induces apoptosis of β-cells by inhibiting their autophagy via adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signaling pathway [ 49 ]. Moreover, in C2C12 myocytes, asprosin treatment augmented insulin resistance by impairing insulin receptor substrate (IRS)-1 and Akt phosphorylation [ 13 ].…”

The Overlooked Transformation Mechanisms of VLCFAs: Peroxisomal β-Oxidation

“…AMPK, for example, promotes FAO by activating the expression of PPARα and ACOX1 [107,108], whereas mTOR promotes the accumulation of FAs by shutting down β-oxidation [109,110]. Hence, these are considered the AMPK-mTOR pathway for regulating β-oxidation [111]. The NAD-dependent protein lysine deacylases of the sirtuin family regulate various physiological functions, from energy metabolism to stress responses [112].…”

Sex‐Specific Effects of Maternal and Post‐Weaning High‐Fat Diet on Adipose Tissue Remodeling and Asprosin Expression in Mice Offspring

“…[ 13 ] It is also observed that asprosin could argument the inflammation response, feeding regulation, cellular dysfunction, and apoptosis. [ 14–16 ] It is worth noting that there is a significant increase in asprosin levels in pregnant women with gestational diabetes and their offspring. [ 17,18 ] However, contradictory findings regarding the expression level of asprosin have been observed, with some studies showing asprosin increased in children with obesity and associated with insulin resistance, [ 19,20 ] and others showing asprosin decreased in children with obesity.…”