PIM1 enhances insulin secretion and inhibits ferroptosis of high glucose-induced pancreatic β-cells through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway

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BACKGROUND: Diabetes mellitus (DM), a chronic metabolic disease, is characterized by long-term hyperglycemia resulting from the defect of insulin production and insulin resistance. The damage and dysfunction of pancreatic β-cells is a main link in DM development. METHODS: In this work, pancreatic β-cell line INS-1E cells were exposed to 30 mM glucose for 48 h to construct an in vitro DM model. For gain-of-function experiments, HG-treated INS-1E cells were transfected with Oe-PIM1 to thoroughly discuss the biological role of PIM1 in HG-injured pancreatic β-cells. Furthermore, to probe into whether JNK/p38 signaling involved in the protective role of PIM1 in HG-injured pancreatic β-cells, HG-treated INS-1E cells were pre-treated with a JNK activator anisomycin (0.01 μM) for 1 h for rescue experiments. RESULTS: It was verified that HG treatment obviously downregulated PIM1 expression in INS-1E cells. PIM1 overexpression enhanced insulin secretion, inhibited ferroptosis and strengthened PINK1/Parkin-mediated mitophagy of HG-treated INS-1E cells. PIM1 overexpression inactivated JNK/p38 signaling pathway in HG-treated INS-1E cells. Activation of JNK/p38 signaling pathway partially abolished the strengthening effects of PIM1 overexpression on PINK1/Parkin-mediated mitophagy in HG-treated INS-1E cells. Upregulation of PIM1 strengthened PINK1/Parkin-mediated mitophagy in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway. Besides, activation of JNK/p38 signaling pathway partially abolished the enhancing effects of PIM1 overexpression on insulin secretion and the suppressive effects of PIM1 overexpression on ferroptosis in HG-treated INS-1E cells. Upregulation of PIM1 enhanced insulin secretion and inhibited ferroptosis in HG-injured pancreatic β-cells via inactivating JNK/p38 signaling pathway. CONCLUSION: In a word, upregulation of PIM1 may alleviate HG-induced pancreatic β-cell injury through strengthening PINK1/Parkin-mediated mitophagy via inactivating JNK/p38 signaling pathway.

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