Abstract
Silk fibroin hydrolysates have been reported to reduce hyperglycemia, but the mechanism has not been determined in Asian type 2 diabetes (T2DM). We hypothesized that the consumption of acid hydrolyzed silk peptides (SPs) alleviates hyperglycemia by improving insulin sensitivity and subsequently normalizing glucose-stimulated insulin secretion in T2DM. We investigated this hypothesis in a partial pancreatectomized (Px) rat model. Px rats was assigned randomly to the following six groups and fed assigned diet for 8 weeks: the Px-control (0.5 g/kg/day dextrin), the SP-L (0.05 g/kg/day), the SP-M (0.1 g/kg/day), the SP-H (0.5 g/kg/day), the positive-control (40 mg/kg/day metformin), or the normal-control (sham-operated rats; 0.5 g/kg/day dextrin). SPs contained high levels of glycine, alanine, and serine. We found SPs dose-dependently increased food efficiency and body weight gain in Px rats. Animals in the Px-control group rats exhibited lower glucose metabolism, as evidenced by impaired glucose-stimulated insulin secretion coupled with impaired insulin sensitivity, and reduced bone mineral density (BMD) and lean body mass (LBM), compared to the normal-control. SPs and metformin similarly partially protected against Px-induced BMD loss in the lumbar spine and femur. Px-induced decreases in LBM were dose-dependently prevented by SPs, and muscle forces in the SP-M and SP-H groups were maintained at the normal-control level. Glucose tolerance was dose-dependently improved by SPs as determined by oral glucose tolerance and oral maltose tolerance tests, and glucose tolerances were similar in the SP-H and positive-control groups. Insulin tolerance, an index of insulin sensitivity, was dose-dependently enhanced by SPs, and the SP-H group exhibited better insulin tolerance than the positive-control group as determined by intraperitoneal insulin sensitivity testing. Insulin secretory capacity assessed using a hyperglycemic clamp improved in the following order: Px-control <SA-L <SA-M <positive-control <SA-H <normal-control. SP-M prevented gut microbiota dysbiosis. In conclusion, SPs administered at 0.1–0.5 g/kg/day improved glucose regulation by potentiating both insulin secretion and insulin sensitivity in non-obese T2DM rats.
Highlights
Diabetes prevalence has dramatically increased worldwide due to improved life expectancy and the increased prevalence of obesity
Silk fibroins can be hydrolyzed by enzymes or acids, and silk fibroins hydrolyzed with a mixture of proteinases were reported to have anti-hyperglycemic activity in diabetic experimental animals [17]
The present study revealed that alleviated hyperglycemia by enhancing insulin sensitivity and glucose-stimulated insulin secretion consumption of silk peptides (SPs) alleviated hyperglycemia by enhancing insulin sensitivity and glucosein an Asian type 2 diabetic animal model
Summary
Diabetes prevalence has dramatically increased worldwide due to improved life expectancy and the increased prevalence of obesity. Westerners have a higher capacity to release insulin from pancreatic β-cells to combat high serum glucose levels and not develop T2DM as as Asians, and Asians are more susceptible to the disease. Sulfonylurea and other insulin secretagogues, often exhaust pancreatic β-cells since they act on ATP-sensitive potassium channels to release insulin regardless of serum glucose levels. These drugs are used in Asian T2DM patients that secrete insulin at low levels and immediately reduce serum glucose levels. They have various side effects such as hypoglycemia, diarrhea, nausea, and abdominal distension due to gas production and exhausted pancreatic β-cell function. Better insulin secretagogues that do not exhaust β-cell mass are needed, as maintaining or increasing pancreatic β-cell mass is important for combating hypoglycemia
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