Abstract
Glucose-stimulated insulin secretion (GSIS) is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM). Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.
Highlights
Type 2 diabetes mellitus (T2DM) is a heterogeneous, multifactorial, polygenic disease characterized by a defect in either insulin secretion and/or action that results in elevated circulating glucose [1]
Geniposide increased insulin secretion by 58% and 38% when INS-1 cells were exposed to 5.5 mM and 11 mM of glucose and in contrast reduced insulin secretion by 35% when stimulated with 33 mM of glucose as compared with the cells treated with the same concentrations of glucose alone
The present study demonstrated that geniposide enhanced Glucose-stimulated insulin secretion (GSIS) in the presence of low or moderately high concentrations of glucose, in line with a previous study [14]
Summary
Type 2 diabetes mellitus (T2DM) is a heterogeneous, multifactorial, polygenic disease characterized by a defect in either insulin secretion and/or action that results in elevated circulating glucose [1]. Impairment of β cell function or cell death due to prolonged exposure to high glucose stimulations in insulin resistance is an important causative factor in the progression of insulin resistance towards T2DM [2,3]. Similar phenomena have been seen in human diabetics as evidenced by findings that supraphysiological glucose concentrations are deleterious to β-cell function and survival, resulting in the alteration of the functional β-cell mass and contributing to the progressive worsening of glucose intolerance in T2DM patients [6,7,8]. It is hypothesized that if pancreatic β cells are protected from over release of insulin in response to high blood glucose concentrations, β cell mass and function may be preserved for a long term benefit
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
