AMPK α1 mediates the protective effect of adiponectin against insulin resistance in INS‐1 pancreatic β cells

Abstract

The fat-derived protein adiponectin is known to reverse the effects of insulin resistance and to lower blood glucose levels. The AMP-activated protein kinase (AMPK) signalling pathway plays a central role in metabolism and energy homeostasis.Here, to investigate the role of AMPK in the protective effect of adiponectin against insulin resistance, we established the model of high-glucose (HG)-and high-lipid (HL)-induced insulin resistance in INS-1 pancreatic β cells. We found that 25mM of glucose and 0.4mM of palmitic acid treatment significantly increased cell apoptosis and impaired insulin secretion in INS-1 cells. However, recombinant human adiponectin dramatically reduced HG-and/or HL-induced cell apoptosis and greatly improved insulin secretion. Interestingly, adiponectin treatment also activated AMPK signalling pathway by increasing the phosphorylation of Thr172 in the AMPK α subunit; 10μM of compound C, a potent AMPK inhibitor, blocked the protective effects of adiponectin against HG/HL-induced insulin resistance. Furthermore, knockout experiments by CRISPR/Cas9 technology showed that AMPK α1, but not AMPK α2, is involved in the protective effects of adiponectin. Taken together, adiponectin reversed the effects of insulin resistance via AMPK α1, which provides a novel insight into the protective mechanism of adiponectin and may be used as a new strategy for the treatment of type 2 diabetes.Significance of the Study: Adiponectin can reverse the effects of insulin resistance and lower blood glucose levels. Here, adiponectin reduced HG/HL-induced cell apoptosis and greatly improved insulin secretion. These effects were blocked by AMPK inhibitor, compound C. Specifically, we found that AMPK α1, but not AMPK α2, mediates the protective effects of adiponectin, which provides a novel insight into the protective mechanism of adiponectin against insulin resistance.

Adiponectin inhibits cardiac arrest/cardiopulmonary resuscitation‑induced apoptosis in brain by increasing autophagy involved in AdipoR1‑AMPK signaling

“…aPn, an adipocyte-derived secretory protein, plays an important role in metabolic (31), anti-inflammatory (32) and anti-oxidative activities (33). a number of studies have reported that aPn also specialized in alleviating myocardial, renal and pancreatic ischemic reperfusion injury by reducing apoptosis (34)(35)(36). our previous study indicated that aPn reduced the number of apoptotic activities from neurons following Gcir induced by ca-cPr (30).…”

The AMPK pathway in fatty liver disease

“…At the same time, a large number of studies have also shown that regulating the production of adipocytokines or the expression of adipocyte-specific genes was one of the most effective approaches to improve IR. For example, adiponectin, as a cytokine secreted by adipocytes, was a specific cytokine of adipocytokines that is most closely related to IR and has the effect of regulating lipid metabolism in the liver ( Caselli 2014 ; Wang et al, 2019 ). Adiponectin could improve insulin sensitivity when it binds to the adiponectin receptor (AdipoR1/2).…”

“…Adiponectin could improve insulin sensitivity when it binds to the adiponectin receptor (AdipoR1/2). Furthermore, adiponectin could activate AMPK activity, which in turn enhances insulin signal transduction of adipose cells, reverses IR, and inhibits the occurrence and development of NAFLD ( Wang et al, 2019 ; Yang et al, 2022 ). Therefore, AMPK may be a potential new target for the prevention and treatment of NAFLD.…”

PRKAA1 predicts prognosis and is associated with immune characteristics in gastric cancer

“…PRKAA1 is the α-subunit of 5-AMP-activated protein kinase (AMPK), which functions as an energy sensor and plays a key role in maintaining cellular metabolic homeostasis (Roa, et al 2018, Wang, et al 2019).…”