Evaluation of the antidiabetic activity of hydrolyzed peptides derived from Juglans mandshurica Maxim. fruits in insulin-resistant HepG2 cells and type 2 diabetic mice

Bioactive peptides derived from plant proteins are promising sources for the development safe hypoglycemics. The present study was designed to investigate the antidiabetic activity of walnut hydrolyzed peptides (WHPs) obtained from the fruit proteins of Juglans mandshurica Maxim. In vitro results showed that WHPs with medium molecular weights (3-10 kDa) exhibited the highest -glucosidase inhibitory rate (61.73%) and significantly increased extracellular glucose consumption in insulin-resistant HepG2 cells. In mice with streptozotocin-induced type 2 diabetes, WHPs with medium molecular weights reduced fasting blood glucose levels by 64.82% and increased insulin secretion by 23.71% and liver glucokinase and glycogen levels by 69.54 and 76.19%, respectively. Furthermore, an analysis of serum lipid profiles showed that WHPs significantly decreased serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. Our results indicate the antidiabetic potential of WHPs and provide evidence to support the application of WHPs in the treatment of diabetes. Practical applications Juglans mandshurica Maxim., commonly known as the Manchurian walnut, is a member of the Juglandaceae plant family. Its fruit is extensively consumed in northeast China and is used in the production of dairy and bakery products, candy, and cooking oil owing to its high protein content (about 30%), abundance of essential amino acids, and easy digestibility. Hence, there has been an immense increase, up to a million hectare, in the area under Manchurian walnut cultivation. The results of the present study indicated thatWHPs showed significant antidiabetic activity by improving alpha-glucosidase activity, glucose metabolism, insulin secretion, and liver glucokinase and glycogen levels as well as by decreasing the fasting blood glucose level. These findings have identified a green source of novel antidiabetic peptides that can either be used as a functional food ingredient in the management of hyperglycemia or developed as a drug for the treatment of type 2 diabetes.