Abstract
Replenishment of insulin-producing pancreatic β-cells would be beneficial in diabetes. The number of β-cells is maintained primarily by self-neogenesis to compensate for β-cell failure, loss or dedifferentiation. We present here a polypeptide vglycin, which was isolated and purified from germinating pea seeds. Vglycin exhibited positive effects in our diabetic models by promoting the proliferation and suppressing the apoptosis and dedifferentiation of β-cells. Vglycin promoted the restoration of β-cells in both young streptozotocin (STZ)-induced type 1 diabetic SD rats and in aged high-fat diet with (or without) STZ-induced type 2 diabetic C57BL/6 mice. We demonstrated that vglycin triggers this positive signaling by activating the insulin receptor and corresponding transcription factors. Impaired insulin sensitivity and glucose tolerance in aged T2DM mice were dramatically improved after long-term vglycin treatment, consistent with the altered level of inflammatory factor IL-1β/6. In addition, energy expenditure and body weights were significantly decreased in the mouse models after vglycin therapy. These results provide insight into the protective effects of vglycin on ameliorating β-cell function in standing glucolipotoxicity. Thus, vglycin may represent a new therapeutic agent for preventing and treating diabetes by replenishing endogenous insulin-positive cells.
Highlights
Diabetes, a heterogeneous disorder with complex etiologies, is characterized by abnormal carbohydrate metabolism caused by insufficient insulin release[1]
Administration of vglycin at a dose of 80 mg/kg/day to T1DM Sprague Dawley (SD) rats caused a significant decrease in both fasting plasma glucose (FPG) and random-fed blood glucose (Fig. 1A,B) during the four-week vglycin treatment period
We examined whether vglycin affects the pancreatic islets of young T1DM SD rats
Summary
A heterogeneous disorder with complex etiologies, is characterized by abnormal carbohydrate metabolism caused by insufficient insulin release[1]. T2DM, the predominant type of diabetes, is characterized by impaired peripheral insulin sensitivity and glucose tolerance, leading to β -cell failure and diminution or dedifferentiation. The regeneration of β -cells occurs via at least two pathways: self-replication and conversion from other cell types. Chronic metabolic stresses such as aging, obesity and overnutrition can result in the failure of β -cell function and mass[14]. We reported that vglycin normalizes fasting plasma glucose (FPG) levels in young type 2 diabetic Wistar rats by improving insulin sensitivity, glucose tolerance and islet restoration, while vglycin did not have toxic effects on organ functions of normal BALB/c mice[21]. Our results provide direct evidence for vglycin as a potential antidiabetic agent, the precise mechanisms remain to be elucidated
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