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Introduction
Diabetes mellitus (DM) is a serious, chronic metabolic disease characterized by persistently elevated
blood sugar levels due to defects in insulin secretion and/or insulin resistance.
With the continuous improvement of people's living standards, as well as the continuous adjustment of human diet and the gradual reduction of exercise, diabetes has become the third largest chronic non-communicable disease
after tumors and cardiovascular diseases.
The International Diabetes Federation (IDF) predicts that by 2035, 10% of the world's population will be diagnosed with diabetes
.
Among them, 90% of diabetic patients have type II diabetes mellitus (T2DM).
Insulin resistance, glucose metabolism, and lipid metabolism disorders are important features
of type II diabetes.
Although the pathogenesis of type II diabetes has not been fully elucidated, a growing body of research suggests that it is associated
with insulin resistance, impaired pancreatic insulin secretion, oxidative stress, and lipid metabolism disorders.
IRS/Akt and AMPK/ACC pathway activation are potential therapeutic targets for improving lipid metabolism and insulin resistance, and the IRS/Akt signaling pathway regulates glucose uptake and intracellular glycogen synthesis
in liver tissue.
In an insulin-resistant state, the IRS/Akt signaling pathway is inhibited, and glucose transport to the plasma membrane is impeded
.
In addition, activation of AMP-activated protein kinase (AMPK) in the liver promotes glucose uptake, insulin sensitivity, and fatty acid oxidation
.
AMPK-mediated acetyl-CoA carboxylase (ACC) phosphorylation inhibits ACC activity, resulting in decreased malonyl-CoA content, FFA levels, and triglyceride synthesis, and increased
β-oxidation.
Therefore, IRS/Akt and AMPK/ACC pathway activation has the potential to modulate glucose metabolism
.
Sea cucumber is China's traditional seafood and important medicinal raw materials
.
In 2016, China's total sea cucumber production reached 174,340 tons
.
During the transport and processing of sea cucumbers, autolysis
often occurs due to the presence of endogenous proteases.
As a result, sea cucumbers are processed into edible parts, and leftover tissues, such as gut and gonadal components, are often processed into fishmeal for animal feed or discarded
as low-value byproducts.
Sea cucumber flower is the gonadal tissue of sea cucumber, and the protein content of sea cucumber flower is as high as 50%, which is a rich resource for protein
.
Peptides are natural substances
with a wide range of sources, easy absorption, and a variety of biological effects.
In view of the high content of sea cucumber gonadal protein, the preparation of sea cucumber flower digest (SCGH) has broad prospects as a potential functional food additive
.
Professor Zhao Moming from the School of Food Science and Engineering of South China University of Technology and Dr.
Wang Tingting from the School of Light Industry and Food Engineering of Guangxi University studied the anti-diabetic effect of SCGH in STZ-induced rats with type II diabetes mellitus, and elucidated the mechanism
by which SCGH improves anti-diabetic ability by alleviating lipid metabolism and insulin resistance.
Results and discussion
Hypoglycemic effect
Type II diabetes is a chronic metabolic disease characterized by hyperglycemia, polydipsia, polyphagia, polyuria, and wasting.
The model group had significant increases in fasting blood glucose, water intake, and glycated glycaemic proteins, significant weight loss, and impaired
glucose tolerance.
However, after 8 weeks of oral administration of metformin and SCGH in diabetic rats, the symptoms of fasting blood glucose, water intake and glycated glycaemic protein were significantly increased, and the symptoms of impaired glucose tolerance were significantly improved, and the results showed that metformin and SCGH treatment could improve the symptoms
of diabetic rats.
Fig.
2 Water intake (A), body weight (B), fasting blood glucose (C), oral glucose tolerance (D), AUC area (E) and glycated hemoglobin (F)
Improve lipid metabolism and insulin resistance
Impaired carbohydrate utilization in patients with T2DM leads to abnormal lipid metabolism, characterized by high LDL-C, TG, and TC, and lowHDL-C.
The serum TG, TC and LDL-C of rats in the model group increased significantly, and in addition, the HOMA-IR and ISI values of the model rats increased significantly (about 332.
83% and 47.
42%, respectively), indicating that STZ-induced diabetic rats had severe lipid metabolism disorders and insulin resistance
.
After 8 weeks of administration, metformin and SCGH improved dyslipidemia while decreasing the increase in HOMA-IR, and these results showed that SCGH could improve lipid metabolism and insulin resistance
in diabetic rats.
Figure 3 (A)TG, (B)TC, (C) HDL-c, (D) LDL-c, (E) serum insulin level, (F) fasting blood glucose level, (G) HOMA-IR, (H) ISI, (I) relative liver weight
Activate IRS/Akt and AMPK signaling pathways
The liver is the main organ of glucose metabolism, and liver damage can enhance insulin resistance, which in turn affects glucose metabolism
.
In this study, SCGH could improve symptoms such as hepatic cord disorder, lipid vacuoles, focal necrosis, central venous congestion and loss of cell boundaries in diabetic
rats.
Moreover, SCGH significantly increased the liver glycogen content in diabetic rats, indicating that SCGH has the potential to
increase glycogen synthesis.
In addition, the protein expression of p-Akt and p-GSK-3β in the liver tissue of the model rat group was reduced, while the protein expression of p-IRS1 was significantly increased, indicating that insulin signaling in the liver of diabetic rats was impaired
.
However, metformin and SCGH treatment significantly increased the protein expression levels of p-Akt and p-GSK-3β in rats with T2DM diabetes and decreased the protein expression
of p-IRS1 in a dose-dependent manner 。 Studies have shown that amino acids such as Pro, Phe, Leu/Ile and Ala can alleviate glucose uptake and insulin resistance by activating the IRTK/PI3K/GLUT4 signaling pathway, and the abundance of Pro (7.
91%), Leu+Ile (7.
99%) and Ala (6.
22%) in SCGH or peptides containing these amino acids may be involved in the activation
of the PI3K/GLUT4 signaling pathway.
The induction of STZ significantly reduced the expression level of p-AMPK in diabetic rats, and the expression level of p-AMPK in the SCGH group was significantly increased by 154.
70% and 141.
26%,
respectively.
In our study, the expression level of p-AMPK in the liver of the model group was significantly reduced
.
However, in STZ-induced diabetic rats, SCGH significantly stimulated phosphorylation
of AMPK.
SCGH helps restore lowered p-AMPK levels
in the liver during insulin resistance.
These data suggest that SCGH has potential hypolipidemic and hypoglycemic effects
in diabetic rats.
The hypoglycemic and lipid-lowering effects of SCGH may be related to
the potential lipid-lowering peptides in the hydrolysate.
In addition, aliphatic amino acids such as Gly, Ala, Val, Ile and Leu can remove bile acids by forming stable complexes with hydrophobic bonds
.
In this study, SCGH is rich in aliphatic amino acids, so we speculate that SCGH can remove bile acids in the body and thus play a hypolipidemic effect
.
Conclusion
SCGH has potent hypoglycemic and lipid-lowering and insulin sensitization effectson STZ-induced diabetic rats.
Underlying molecular mechanistic studies have shown that SCGH activates the PI3K/Akt and AMPK signaling pathways, further regulating the expression of GSK-3β and ACC proteins, thereby promoting lipid metabolism and improving insulin sensitivity
.
First author bio
Wang Tingting, female, Ph.
D.
in Engineering, PhD candidate at Guangxi University, mainly focuses on the preparation and efficacy of bioactive peptides, enzymatic hydrolysis mechanism and functional characteristics of enzymatic hydrolyses, peptide structure and characterization, animal and cell experimental research, processing and utilization
of functional products.
He has published 4 academic papers in domestic and foreign journals, including 3 SCI papers and 2 first-author papers
.
About the corresponding author
Zhao Moming, male, doctoral supervisor, special allowance expert of the State Council, Changjiang Scholar Distinguished Professor, national training object of the New Century Millions of Talents Project, outstanding talent of Guangdong Special Branch Program, person in charge
of "Food Nutrition and Health Discipline Innovation Introduction Base" and "Guangdong Food Green Processing and Nutrition Regulation Engineering Center".
As the project leader, he has presided over more than 100 major projects including the demonstration project of the National Development and Reform Commission, the national "Twelfth Five-Year Plan" and "Eleventh Five-Year Plan" support plan projects, the national "863" project, the National Natural Science Foundation of China and more than
100 horizontal projects.
It has overcome a series of common key technologies in the preparation of high-quality functional proteins, functional peptides and flavor-forming bases, as well as a series of key technologies
in the production of high-quality soy sauce, beer and yogurt.
Related key technologies and products have been transformed in more than 30 large and medium-sized enterprises in China, and have won 3 second prizes of National Science and Technology Progress Award and 4 first prizes of Guangdong Science and Technology Progress Award, which have produced significant social and economic benefits
.
He has been authorized more than 100 national invention patents, published 395 papers indexed by SCI, and has an H-index of 51, entering the top 1% of international agricultural scientists ESI ranking (46/5732, 2020).
Tingting Wanga,b, Lin Zhengb,c, Shuguang Wangb,c, Mouming Zhaoa,b,c,*, Xiaoling Liua,*
a College of Light Industry and Food Engineering, Guangxi University, Nanning 530004, China
b Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou 510650, China
c School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China
*Corresponding author.
E-mail address: zmmgxu@gxu.
edu.
cn; liuxling@gxu.
edu.
cn
The present study investigated the anti-diabetic activity and potential mechanisms of sea cucumber gonad hydrolysates (SCGH) in a rat model of type II diabetes induced by streptozotocin (STZ) combined with high-fat diet (HFD).
Results showed that SCGH significantly reduced water intake, fasting blood glucose level and glycated hemoglobin level.
Moreover, the oral glucose tolerance, insulin resistance and plasma lipid level in diabetic rats were also alleviated.
Furthermore, histological analysis showed that SCGH effectively protected the tissue structure of liver.
In addition, mechanism studies showed that SCGH improved glucose metabolism via activating the IRS/Akt signaling pathway, and promoted lipid metabolism via activating the AMPK signaling pathway.
In summary, these findings suggested that SCGH have potential anti-diabetic effects by improving insulin resistance and lipid metabolism disorders.
Reference:
WANG T T, ZHENG L, WANG S G, et al.
Anti-diabetic and anti-hyperlipidemic effects of sea cucumber (Cucumaria frondosa) gonad hydrolysates in type II diabetic rats[J].
Food Science and Human Wellness, 2022, 11(6): 1614-1622.
DOI:10.
1016/j.
fshw.
2022.
06.
020.
