Abstract
Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic β-cell, we investigated the effects of hydrolyzed SF on the pancreatic β-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic β-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic β-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.
Highlights
Diabetes mellitus (DM) is a kind of metabolic disease, and its prevalence has steadily increased worldwide over in the last three decades [1]
We demonstrated that hydrolyzed silk fibroin (SF) treatment had protective effects against high glucose in the in vitro system [10] and ameliorated diabetic dyslipidemia in the db/db mouse model [11]
A recent study demonstrated that hydrolyzed SF regulates the transcription factors, which in the tissue regeneration [16,17]; we investigated whether hydrolyzed SF treatment can promote involved in the tissue regeneration [16,17]; we investigated whether hydrolyzed SF treatment the regeneration of pancreatic β-cells in a mouse model
Summary
Diabetes mellitus (DM) is a kind of metabolic disease, and its prevalence has steadily increased worldwide over in the last three decades [1]. Molecules 2020, 25, 3259 regulator of glucose metabolism; insulin therapy could be the best solution for T1DM. T2DM is characterized by the malfunction, dedifferentiation, and death of the pancreatic β-cells, causing significant increases in the risk of cardiovascular disease, renal dysfunction, retinopathy, and neuropathy [3,4]. Anti-diabetes drugs often cause side effects such as nausea, low glucose levels, weight gain, and bloating. While various T2DM clinical treatments can improve the blood glucose levels and prolong patient survival, the efficacy of the anti-diabetic drugs is still limited. One of the effective anti-diabetic therapeutic approaches is to increase or replace the lost pancreatic β-cells by regeneration
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