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Metformin may protect beta-cell function and insulin secretion capacity by relieving glucotoxicity and lipotoxicity

Shangyu CHEN, Zhe DAI, Huawei WANG, Yancheng XU


Objective: To investigate the protective effect of metformin on beta cells. Methods NIT-1 cells were treated with high glucose and/or palmitate pretreatment, with/without metformin. Cell apoptosis, intracellular reactive oxygen species (ROS) production and glucose-stimulated insulin secretion were measured. Cleaved caspase-3, cleaved caspase-9, and p-JNK were measured to evaluated apoptosis and activation of the ER stress pathway. Results (1) The addition of metformin may partly reverse the impairment of insulin secretion in NIT-1 cells with high glucose and/or palmitate. (2) After metformin pre-treatment, ROS production and cell apoptosis were significantly decreased in NIT-1 cells treated with palmitate and/or high glucose. (3) After metformin pretreatment, expression of cleaved caspase 3, cleaved caspase 9, and p-JNK were significantly decreased in NIT-1 cells treated with palmitate and/or high glucose, in consistence with the decreased apoptosis after metformin pretreatment in NIT-1 cells. Conclusion Metformin may help to decrease glucose variability and preserve beta-cell function. The mechanism may be related to decreases in oxidative stress and ER stress induced by glucotoxicity and lipotoxicity.

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