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

Background: Type 2 diabetes mellitus is characterized by insulin resistance and pancreatic beta-cell dysfunction. A decrease in beta-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 beta-cells to clarify the mechanisms underlying its anti-diabetic function. Methods: Mulberry leaves (Morus alba L.) were dried at 180 degrees 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 beta-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 beta-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 beta-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 beta-cell mass, at least in part, by suppressing endoplasmic reticulum stress in Type 2 diabetes mellitus mouse models.