The adverse effects of chronic low-dose exposure to nonylphenol on type 2 diabetes mellitus in high sucrose-high fat diet-treated rats

Islets. 2018 Jan 2;10(1):1-9. doi: 10.1080/19382014.2017.1404211. Epub 2017 Dec 7.


Objectives: Although it has been shown that exposure to environmental endocrine disruptors (EDCs) has been implicated as a potential risk factor for metabolic disease, information on adverse effect of chronic low-dose exposure to nonylphenol (NP), on the development and progress of type 2 diabetes mellitus (T2DM) is scarce. NP, as an EDC, is a ubiquitous degradation product of nonylphenol polyethoxylate (NPE) that is primarily used in cleaning and industrial processes.

Method: Eighty Sprague-Dawley rats were assigned into 8 groups (n = 10 per group): rats fed a normal-diet (ND) as the control (C-ND); rats fed a normal diet and were gavaged with NP at a dose level of 0.02 μg/kg/day (NP-L-ND), 0.2 μg/kg/day (NP-M-ND) or 2 μg/kg/day (NP-H-ND), respectively; rats fed a high-sucrose/high-fat diet (HSHFD) as the HSHFD control (C-HSHFD); rats fed a HSHFD and were gavaged with NP at a dose level of 0.02 μg/kg/day (NP-L-HSHFD), 0.2 μg/kg/day (NP-M-HSHFD) or 2 μg/kg/day (NP-H-HSHFD), respectively.

Result: On day 180, the rats in the groups treated with NP-M-HSHFD and NP-H-HSHFD showed significant increases in body weight (p < 0.05) in comparison with the C-ND group. Fast blood glucose (FBG) level in the NP-M-HSHFD and NP-H-HSHFD groups was higher than that in the C-ND group (F = 96.17, p < 0.001). The fast serum insulin (FINS) level of rats was lower in both the NP-M-HSHFD and NP-H-HSHFD groups compared with the C-ND group (F = 145.56, p < 0.001). Serum leptin (LEP) level in both the NP-M-HSHFD and NP-H-HSHFD groups was lower when compared with the C-ND group (F = 34.62, p < 0.001). The effect of NP at the dose level of 0.2 μg/kg/day on FBG, serum FINS and LEP levels in rats was greatest among the treatment groups (p < 0.05). Oral glucose tolerance test showed increased area under the curve (AUC) in treatment groups at week 12 (p < 0.05). A decrease of pancreatic islet numbers and size was exhibited in the pancreatic tissue of NP-M-HSHFD and NP-H-HSHFD treated rats compared with C-ND treated rats. Co-exposure to NP and HSHFD causes inflammatory changes histologically.

Conclusion: Chronic low-dose exposure to NP might induce impaired glucose tolerance, which further lead to insulin resistance, and pancreatic β cell insulin secretion deficiency, ultimately increase the risk of T2DM. Moreover, additive toxic effects of NP and HSHFD on pancreatic beta-cell function and glucose metabolism have been identified in rats as well.

Keywords: Environmental endocrine disruptors; High-sucrose-high-fat diet; Nonylphenol; Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / pathology*
  • Diet, High-Fat* / adverse effects
  • Dietary Carbohydrates / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Male
  • Phenols / administration & dosage*
  • Phenols / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Sucrose / pharmacology*
  • Toxicity Tests, Chronic


  • Dietary Carbohydrates
  • Phenols
  • Sucrose
  • nonylphenol

Grant support

This work was supported by the foundation of the National Natural Science Foundation of China (81360439); Fund of Department of Science and Technology of Guizhou Province, China (LH[2014]7543, LH[2015]7521); Youth Foundation of Department of Education of Guizhou Province (KY[2013]198); bidding project of Zunyi Medical University of China (2013F-68, 2016F-784); Fund for Key Discipline Construction in Zunyi Medical University (2015); Scientific and Technological Fund of Department of Health of Guizhou Province, China (Fund No. gzwjkj2016-1-045); and the Excellent Youth Science and Technique Talents of Guizhou Province [2017]5612.