Work

Bradykinin attenuates NiSO4-induced autophagy in MIN6 cells and protects islet function in mice by regulating the PI3K/AKT/mTOR signaling pathway

Year: 2024

Type: article

Abstract: Previous studies have shown that nickel sulfate (NiSO 4 ) increases autophagy in thyroid cells and tissues. As an important organ of the endocrine system , the pancreas not only contributes to the exocrine function of digestion but also has the endocrine function of regulating blood sugar. However, it remains unknown whether NiSO 4 increases pancreatic autophagy. Bradykinin (BK) is an important component of the kallikrein–kinin system (KKS) and has many biological functions , such as reducing autophagy. The purpose of the present study was to explore the effects of BK on NiSO 4 -induced changes in pancreatic endocrine function . The present results demonstrate that NiSO 4 increases fasting blood glucose (FBG) within a certain range and decreases insulin levels in mice . Moreover, NiSO 4 triggers incomplete autophagy in MIN6 cells by upregulating microtubule-associated protein 1 light chain 3-II (LC3II) and Beclin 1 but downregulating p62. Mechanistically, NiSO 4 leads to abnormal activation of autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway . Moreover, BK decreases FBG and increases insulin secretion in mice exposed to NiSO 4 . Light microscopy and transmission electron microscopy (TEM) analyses revealed that BK pretreatment partially restores MIN6 cell viability and decreases the number of autophagic bodies. BK significantly upregulates the protein levels of LC3II and Beclin1 but downregulates p62 in NiSO 4 -induced MIN6 cells. In addition, BK increases the levels of phosphorylated phosphatidylinositol 3-kinase (P-PI3K), phosphorylated protein kinase B (P-AKT) and mammalian target of rapamycin (mTOR). Most of these effects of BK are reversed by treatment with the HOE140 B2R inhibitor. The present results suggested that BK ameliorates NiSO 4 -induced pancreatic β-cell dysfunction through B2R-mediated activation of the PI3K/AKT/mTOR signaling pathway and inhibition of autophagy.

Source: Biochemical and Biophysical Research Communications

DOI: 10.1016/j.bbrc.2024.151265

Authors: Zhuanping Wang, Hui Chen

Institutions: Lanzhou University Second Hospital, Lanzhou University

Language: English

Topic: Pancreatic function and diabetes

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $2,880