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Endocrine

, Volume 54, Issue 2, pp 360–370 | Cite as

Deteriorated high-fat diet-induced diabetes caused by pancreatic β-cell-specific overexpression of Reg3β gene in mice

  • Xiaoquan Xiong
  • Qing Li
  • Wei Cui
  • Zu-Hua GaoEmail author
  • Jun-Li LiuEmail author
Original Article

Abstract

Reg family proteins have long been implicated in islet β-cell proliferation, survival, and regeneration. In our previous study, we reported that Reg3β overexpression did not increase islet growth but prevented streptozotocin-induced islet damage by inducing specific genes. In order to explore its role in type 2 diabetes (T2D), we established high-fat diet (HFD)-induced obesity and diabetes in RIP-I/Reg3β mice. Glucose and insulin tolerance tests, immunofluorescence for insulin, eIF2α, and GLUT2 in islets, Western blots on phosphorylated AMPKα and hepatic histology were performed. Both RIP-I/Reg3β and wild-type mice gained weight rapidly and became hyperglycemic after 10 weeks on the HFD. However, the transgenic mice exhibited more significant acceleration in blood glucose levels, further deterioration of glucose intolerance and insulin resistance, and a lower intensity of insulin staining. Immunofluorescence revealed similar magnitude of islet compensation to a wild-type HFD. The normal GLUT2 distribution in the transgenic β-cells was disrupted and the staining was obviously diminished on the cell membrane. HFD feeding also caused a further decrease in the level of AMPKα phosphorylation in the transgenic islets. Our results suggest that unlike its protective effect against T1D, overexpressed Reg3β was unable to protect the β-cells against HFD-induced damage.

Keywords

Insulin resistance GLUT2 AMPKα Aging Hepatic steatosis eIF2α 

Notes

Acknowledgments

We would like to thank Dr. Louise Larose for her instructions on ER stress tests and Carolynna Olha for the English revision and editing of this manuscript. This work was supported by the Canadian Institutes of Health Research (Grant MOP-84389), Canadian Diabetes Association (OG-3-11-3469-JL) and a bridge fund from the Research Institute of the McGill University Health Centre (RI-MUHC) to JLL. QL received support from the China Scholarship Council (201208370055). ZHG was supported by the RI-MUHC.

Compliance with ethical standards

Conflicts of interest

All authors declared there were no conflicts of interest.

Supplementary material

12020_2016_998_MOESM1_ESM.tif (1.3 mb)
Supplemental Figure 1. Interlobular fat deposition within the pancreatic tissues of HFD- but not Chow-fed mice. At the end of the 10-week HFD feeding, pancreatic sections were stained with HE, the brown arrows indicate fat deposition in the form of bubbles. Representative images of N=5. Supplementary material 1 (TIFF 1345 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Fraser Laboratories for Diabetes Research, Department of MedicineRI-McGill University Health CentreMontrealCanada
  2. 2.Department of EndocrinologyThe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina
  3. 3.Department of PathologyRI-McGill University Health CentreMontrealCanada
  4. 4.Montreal Diabetes Research CentreMontrealCanada

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