ABSTRACT
Objective:To evaluate the effects of ketogenic diet(KD) on pancreatic β-cell dedifferentiation in db/db mice.Methods:In animal study, 8-week-old db/db male mice with type 2 diabetes mellitus(T2DM) were randomly divided into 3 groups: T2DM model group(ND), KD group, 75% caloric restriction(CR) group, and male C57BL/6 mice of the same age as normal control group(C) fed with standard diet. Both C and ND groups were on ad lititum feeding of chow, the KD group was free to eat the ketogenic diet, and the CR group was the positive control group, consuming 75% of the calories of the ND group every day. Four weeks after different diet intervention, body weight, fasting blood glucose, fasting insulin, glucose tolerance and blood β-hydroxybutyric acid(BHB) were measured. Morphology and structure of pancreatic islet was observed by hematoxylin-eosin staining(HE). Immunofluorescence co-staining was used to observe the expression of mouse pancreatic β-cell specific transcription factors.Results:After 4 weeks diet intervention, the fasting blood glucose, insulin and the area under the curve of blood glucose in KD group was significantly decreased( P<0.05); When compared with ND group, the morphology and structure of the islets in the KD group were more regular, and the number of islet cells increased as revealed with HE staining. Pancreatic immunofluorescence co-assay showed that KD not only restored the number and arrangement of β-cells and the ratio of β/α-cell in the pancreatic islets, but also reversed the expression of specific β-cell transcription factors such as pancreatic duodenal homeobox factor-1(PDX1). Conclusion:KD can reduce fasting blood glucose, fasting insulin and improve glucose tolerance in db/db mice, which may be related to its ability to restore the expression of specific β-cell transcription factors and reverse the dedifferentiation of pancreatic β-cells.
ABSTRACT
Ketogenic diet(KD) has been used for centuries in the treatment of epilepsy, which can restrict calorie and liquid intake, with significant therapeutic effects. In recent years, KD has been proved to have therapeutic effects in other fields, such as obesity, diabetes, hypertension, cancer, Alzheimer′s disease and other chronic diseases. KD has a positive effect on the treatment of many diseases, but the high proportion of fat intake in KD process, as well as too little intake of carbohydrates, proteins and trace elements will lead to a very uneven absorption of nutrients. Therefore, the use of KD to treat disease may cause a variety of adverse reactions, and its long-term results are the subjects of controversy. The purpose of this review is to summarize the literature of KD adverse effects and their prevention and treatment methods, in order to provide guidance and assistance to clinical administration.
ABSTRACT
Ketogenic diet(KD) has been used for centuries in the treatment of epilepsy, which can restrict calorie and liquid intake, with significant therapeutic effects. In recent years, KD has been proved to have therapeutic effects in other fields, such as obesity, diabetes, hypertension, cancer, Alzheimer′s disease and other chronic diseases. KD has a positive effect on the treatment of many diseases, but the high proportion of fat intake in KD process, as well as too little intake of carbohydrates, proteins and trace elements will lead to a very uneven absorption of nutrients. Therefore, the use of KD to treat disease may cause a variety of adverse reactions, and its long-term results are the subjects of controversy. The purpose of this review is to summarize the literature of KD adverse effects and their prevention and treatment methods, in order to provide guidance and assistance to clinical administration.