Administration of mulberry leaves maintains pancreatic β-cell mass in obese/type 2 diabetes mellitus mouse model

BMC Complement Med Ther. 2020 May 6;20(1):136. doi: 10.1186/s12906-020-02933-4.


Background: Type 2 diabetes mellitus is characterized by insulin resistance and pancreatic β-cell dysfunction. A decrease in β-cell mass, which occurs during the progression of Type 2 diabetes mellitus, contributes to impaired insulin secretion. Mulberry leaves contain various nutritional components that exert anti-diabetic and anti-atherogenic effects. The present study analyzed the effects of mulberry leaf intake on pancreatic β-cells to clarify the mechanisms underlying its anti-diabetic function.

Methods: Mulberry leaves (Morus alba L.) were dried at 180 °C for 8 s in a hot-air mill and fed to obesity/Type 2 diabetes mellitus db/db mouse models at 5% (w/w) as part of a normal diet from 7 to 10, 15, or 20 weeks of age. An intraperitoneal glucose tolerance test was then performed on the mice. To evaluate the β-cell mass, the pancreas was subjected to immunohistological analysis with an anti-insulin antibody. A TUNEL assay and immunohistological analysis with a proliferation marker was also performed. Expression levels of endoplasmic reticulum stress-responsible genes and proliferation markers were assessed by quantitative RT-PCR.

Results: Intake of mulberry leaves maintained the β-cell function of db/db mice. Moreover, oral administration of mulberry leaves significantly decreased cell death by reducing endoplasmic reticulum stress in the pancreas. Mulberry leaves significantly increased proliferation of β-cells and the expression of pancreatic duodenal homeobox1 mRNA in the pancreas.

Conclusion: Considered together, these results indicate that dietary mulberry leaf administration can maintain insulin levels and pancreatic β-cell mass, at least in part, by suppressing endoplasmic reticulum stress in Type 2 diabetes mellitus mouse models.

Keywords: Endoplasmic reticulum stress; Mulberry leaves; Obesity; Type 2 diabetes; β-Cell.

MeSH terms

  • Administration, Oral
  • Animals
  • Blood Glucose
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress / drug effects
  • Insulin / blood
  • Insulin-Secreting Cells / cytology*
  • Japan
  • Mice
  • Mice, Obese
  • Morus*
  • Phytotherapy*
  • Plant Leaves*


  • Blood Glucose
  • Insulin