Abstract
In both type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction of β-cell, leading to the impaired insulin secretion. Here, we show that dietary supplementation of baicalein, a flavone isolated from the roots of Chinese herb Scutellaria baicalensis, improved glucose tolerance and enhanced glucose-stimulated insulin secretion (GSIS) in high-fat diet (HFD-) induced middle-aged obese mice. Baicalein had no effect on food intake, body weight gain, circulating lipid profile, and insulin sensitivity in obese mice. Using another mouse model of type 2 diabetes generated by high-fat diet (HFD) feeding and low doses of streptozotocin injection, we found that baicalein treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in these middle-aged obese diabetic mice, which are associated with the improved islet β-cell survival and mass. In the in vitro studies, baicalein significantly augmented GSIS and promoted viability of insulin-secreting cells and human islets cultured either in the basal medium or under chronic hyperlipidemic condition. These results demonstrate that baicalein may be a naturally occurring antidiabetic agent by directly modulating pancreatic β-cell function.
Highlights
Diabetes mellitus is a growing public health concern in the United States, presently affecting 25.8 million or 8.3% of the American population [1]
Baicalein (98% pure by HPLC) for in vivo studies was purchased from Xi’An Yile Bio-Tech Company, China; ultrasensitive rat insulin enzyme-linked immunosorbent assay (ELISA) kits were obtained from Mercodia (Winston-Salem, NC); the active form of the caspase-3 antibody was from BD Biosciences (San Jose, CA); the rabbit polyclonal anti-insulin antibody was from Abcam (Cambridge, MA); the ImmPRESS Anti-rabbit Ig Polymer Detection kit, Vector NovaRED peroxidase substrate kit, and Vector SG peroxidase substrate kits were from Vector laboratories (Burlingame, CA); cell viability assay kits were from Promega (Madison, WI); and the BrdU ELISA kit for the cell proliferation assay was from Roche Applied Sciences (Indianapolis, IN)
Recent studies showed that baicalin, the glucuronide form of baicalein, may exert beneficial effects on diabetes mellitus or diabetes-related complications [14,15,16]
Summary
Diabetes mellitus is a growing public health concern in the United States, presently affecting 25.8 million or 8.3% of the American population [1]. Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease leading to the destruction of pancreatic β-cells, whereas type 2 diabetes (T2D) is due to a combination of peripheral insulin resistance and loss of functional β-cell mass [4,5,6,7]. In both T1D and T2D, inadequate β-cell mass and β-cell dysfunction leading to impaired insulin secretion are central to the deterioration of glycemic control [8]. The search for novel and cost-effective agents that can enhance β-cell function and preserve β-cell mass is important to provide effective treatment for diabetes
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