Low-level lead exposure promotes hepatic gluconeogenesis and contributes to the elevation of fasting glucose level.

Lead (Pb) is considered an endocrine-disrupting chemical. However, few studies have investigated the effects of low-level Pb exposure on plasma glucose levels. Herein, we aimed to investigate whether low-level Pb exposure causes elevated plasma glucose levels and the possible mechanisms involved. We conducted a cross-sectional study of 5747 participants from 16 sites in China. The participants underwent measurements of anthropometric factors, blood lead level (BLL) and fasting plasma glucose (FPG). Wistar rats were exposed to 0.05% Pb through drinking water or fed with a high-fat diet (HFD) for 28 weeks. The relevant parameters of glucose homeostasis, hepatic glucose production (HGP) and gene expression levels of hepatic gluconeogenesis enzymes, including phosphoenolpyruvate carboxy kinase (PEPCK), glucose-6-phosphatase (G6PC) and fructose-1,6-bisphosphatase (FBP1), were measured. In addition, gene expression levels of gluconeogenesis enzymes were also measured in HepG2 cells administered with different concentrations of lead acetate for 24 h. In humans, after adjusting for confounders, the odds of having High_FPG (≥5.6 mmol/L) were significantly increased by 25% in the participants in the fourth BLL quartile (OR 1.25, 95% CI 1.05, 1.49). In the animals exposed to 0.05% Pb, FPG, HGP and hepatic gene expression levels of PEPCK, G6PC and FBP1 were increased. In addition, the mRNA expression levels of PEPCK, G6PC and FBP1 in HepG2 cells were also increased in response to Pb exposure. These findings support the possibility that low-level Pb exposure may increase HGP by affecting key enzymes of hepatic gluconeogenesis, eventually resulting in impaired FPG and hyperglycemia. Copyright © 2021 Elsevier Ltd. All rights reserved.

Citation

Heng Wan, Bin Wang, Yuke Cui, Yuying Wang, Kun Zhang, Chi Chen, Fangzhen Xia, Lin Ye, Li Wang, Ningjian Wang, Yingli Lu. Low-level lead exposure promotes hepatic gluconeogenesis and contributes to the elevation of fasting glucose level. Chemosphere. 2021 Aug;276:130111

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PMID: 33691221

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