Abstract
The aim of our study was to investigate the effect of three lignans (schisandrol A, schisandrol B, and schisandrin C) on insulin secretion in rat INS-1 pancreatic β-cells and glucose uptake in mouse C2C12 skeletal muscle cells. Schisandrol A and schisandrin C enhanced insulin secretion in response to high glucose levels with no toxic effects on INS-1 cells. The effect of schisandrin C was superior to that of gliclazide (positive control), a drug commonly used to treat type 2 diabetes (T2D). In addition, western blot analysis showed that the expression of associated proteins, including peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox 1 (PDX-1), phosphatidylinositol 3-kinase (PI3K), Akt, and insulin receptor substrate-2 (IRS-2), was increased in INS-1 cells after treatment with schisandrin C. In addition, insulin secretion effect of schisandrin C were enhanced by the Bay K 8644 (L-type Ca2+ channel agonist) and glibenclamide (K+ channel blocker), were abolished by the nifedipine (L-type Ca2+ channel blocker) and diazoxide (K+ channel activator). Moreover, schisandrin C enhanced glucose uptake with no toxic effects on C2C12 cells. Western blot analysis showed that the expression of associated proteins, including insulin receptor substrate-1 (IRS-1), AMP-activated protein kinase (AMPK), PI3K, Akt, glucose transporter type 4 (GLUT-4), was increased in C2C12 cells after treatment with schisandrin C. Schisandrin C may improve hyperglycemia by enhancing insulin secretion in pancreatic β-cells and improving glucose uptake into skeletal muscle cells. Our findings may provide evidence that schisandrin C may be beneficial in devising novel anti-T2D strategies.
Highlights
We investigated whether the three lignans could enhance glucose-stimulated insulin secretion (GSIS) without cytotoxicity to INS-1 cells
We confirmed whether schisandrol A, schisandrol B, and schisandrin C at non-toxic concentrations led to an increase in GSIS
INS-1 cells treated with schisandrin C showed increased protein expression of peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox 1 (PDX-1), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt compared with the untreated controls
Summary
Type 2 diabetes (T2D) is a common metabolic disorder with a steadily increasing global prevalence. It is principally characterized by decreased insulin secretion [1], which involves the mechanism mainly known as glucose-stimulated insulin secretion (GSIS). Impaired GSIS in obesity and insulin-resistant conditions may underlie the transition to T2D [3]. In the T2D, skeletal muscle as a main site for insulin-induced glucose uptake after glucose intake become resistance to the action of insulin, which leads to impaired glucose uptake [4]. Researching anti-T2D drugs based on understanding the mechanisms involved in GSIS in pancreatic β-cells and glucose uptake in skeletal muscle cells could be the foundation of prevention strategies for T2D
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