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Cadmium exposure decreases fasting blood glucose levels and exacerbates type-2 diabetes in a mouse model

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Abstract

Purpose

Although the effects of cadmium (Cd) on the development of diabetes have been extensively investigated, the relationship between Cd exposure and the severity of established diabetes is unclear. Herein, we investigate the effects of long-term exposure to Cd in a streptozotocin-induced mouse model of type-2 diabetes mellitus (T2DM) and the underlying mechanism.

Methods

C57BL/6 Mice were divided into the following four groups: (1) control group; (2) Cd-exposed group; (3) diabetic group; (4) Cd-exposed diabetic group. Cd exposure was established by the administration of 155 ppm CdCl2 in drinking water. After 25 weeks of treatment, serum fasting glucose and insulin were measured. Meanwhile, the liver and pancreas specimens were sectioned and stained with Hematoxylin and eosin. Gluconeogenesis, glycolysis, lactate concentration, and fibrosis in liver were evaluated.

Results

Clinical signs attributable to diabetes were more apparent in Cd-exposed diabetic mice, while no effects of Cd exposure were found on non-diabetic mice. Cd exposure significantly decreased fasting blood glucose (FBG) levels in diabetic group. We further demonstrated that the glycolysis related hepatic enzymes, pyruvate kinase M2 (PKM-2) and lactic dehydrogenase A (LDHA) were both increased, while the gluconeogenesis related hepatic enzymes, phosphoenolpyruvate-1 (PCK-1) and glucose-6-phosphatase (G6Pase) were both decreased in Cd exposed diabetic mice, indicating that Cd increased glycolysis and inhibited gluconeogenesis in diabetic model. Moreover, lactate accumulation was noted accompanied by the increased inflammation and fibrosis in the livers of diabetic mice following Cd exposure.

Conclusions

Cd exposure disturbed glucose metabolism and exacerbated diabetes, providing a biological relevance that DM patients are at greater risk when exposed to Cd.

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Fig. 1: Cd decreased fasting blood glucose and serum insulin concentrations in diabetic mice.
Fig. 2: Cd enhanced glycolysis and inhibited gluconeogenesis in diabetic mice.
Fig. 3: Cd increases liver lactate and inflammation levels in diabetic mice.
Fig. 4: Cd promoted liver fibrosis in diabetic mice.

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Funding

This research was supported by the National Natural Scientific Funding of China (Nos. 81773414, 81703209 and 81872622) and this is a project funded by Priority Academic Program Development of Jiangsu Higher Education Insitiitutions (PAPD).

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Authors and Affiliations

  1. School of Public Health, Soochow University, 215123, Suzhou, China

    Mengyang Li, Xiuxiu Liu, Bingyan Li, Jiafu Li, Jie Zhang & Zengli Zhang

  2. The Shishan Community Hospital of SND in Suzhou, 215011, Suzhou, China

    Shuai Wang

  3. The Fifth People’s Hospital in Suzhou, 215007, Suzhou, China

    Zhijie Sheng

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  1. Mengyang Li
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  2. Shuai Wang
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Contributions

M.L., S.W., and Z.Z. conceived and designed the experiments; M.L., and S.W. performed the experiments; B.L., S.W., X.L., and Z.S. contributed reagents/materials/analysis tools; J.Z., M.L., X.L., and J.L. analyzed the data; M.L. and Z.Z. wrote the paper.

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Correspondence to Jie Zhang or Zengli Zhang.

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Li, M., Wang, S., Liu, X. et al. Cadmium exposure decreases fasting blood glucose levels and exacerbates type-2 diabetes in a mouse model. Endocrine 76, 53–61 (2022). https://doi.org/10.1007/s12020-021-02974-w

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