Because insulin released by the β-cells of pancreatic islets is the main regulator of glucose levels, the quantitative modeling of their glucose-stimulated insulin secretion is of obvious interest not only to improve...Because insulin released by the β-cells of pancreatic islets is the main regulator of glucose levels, the quantitative modeling of their glucose-stimulated insulin secretion is of obvious interest not only to improve our understanding of the processes involved, but also to allow better assessment of β -cell function in diabetic patients or islet transplant recipients as well as the development of improved artificial or bioartificial pancreas devices. We have recently developed a general, local concentrations-based multiphysics computational model of insulin secretion in avascular pancreatic islets that can be used to calculate insulin secretion for arbitrary geometries of cultured, perifused, transplanted, or encapsulated islets in response to various glucose profiles. Here, experimental results obtained from two different dynamic glucose-stimulated insulin release (GSIR) perifusion studies performed by us following standard procedures are compared to those calculated by the model. Such perifusion studies allow the quantitative assessment of insulin release kinetics under fully controllable experimental conditions of varying external concentrations of glucose, oxygen, or other compounds of interest, and can provide an informative assessment of islet quality and function. The time-profile of the insulin secretion calculated by the model was in good agree- ment with the experimental results obtained with isolated human islets. Detailed spatial distributions of glucose, oxygen, and insulin were calculated and are presented to provide a quantitative visualization of various important aspects of the insulin secretion dynamics in perifused islets.展开更多
We reported a new protocol for constructing a unique indolizine-containing perifused tricycle by combining a copper relay-catalyzed three-component cascade with a 12πelectrocyclization reaction from readily available...We reported a new protocol for constructing a unique indolizine-containing perifused tricycle by combining a copper relay-catalyzed three-component cascade with a 12πelectrocyclization reaction from readily available starting materials.The indolizine generated by the copper-catalyzed multicomponent cascade is a key intermediate obtained during subsequent spontaneous electrocyclization.In contrast to the traditional SEAr reaction model,this study is based on the tetraene-like character of indolizine to form an aromatic heterocycle 12πelectron system that can spontaneously trigger 12πelectrocyclization.This transformation can not only enhance the reactivity of indolizine but also improve the electrocyclization model.This convergent strategy can significantly enhance synthetic versatility,and the resulting perifused cycle products containing indolizine may serve as a molecular platform for the discovery and characterization of pharmaceuticals and functional molecules.展开更多
文摘Because insulin released by the β-cells of pancreatic islets is the main regulator of glucose levels, the quantitative modeling of their glucose-stimulated insulin secretion is of obvious interest not only to improve our understanding of the processes involved, but also to allow better assessment of β -cell function in diabetic patients or islet transplant recipients as well as the development of improved artificial or bioartificial pancreas devices. We have recently developed a general, local concentrations-based multiphysics computational model of insulin secretion in avascular pancreatic islets that can be used to calculate insulin secretion for arbitrary geometries of cultured, perifused, transplanted, or encapsulated islets in response to various glucose profiles. Here, experimental results obtained from two different dynamic glucose-stimulated insulin release (GSIR) perifusion studies performed by us following standard procedures are compared to those calculated by the model. Such perifusion studies allow the quantitative assessment of insulin release kinetics under fully controllable experimental conditions of varying external concentrations of glucose, oxygen, or other compounds of interest, and can provide an informative assessment of islet quality and function. The time-profile of the insulin secretion calculated by the model was in good agree- ment with the experimental results obtained with isolated human islets. Detailed spatial distributions of glucose, oxygen, and insulin were calculated and are presented to provide a quantitative visualization of various important aspects of the insulin secretion dynamics in perifused islets.
基金The authors thank NSFC(grant nos.21772019 and 22371024)support from the Venture&Innovation Support Program for Chongqing Overseas Returnees(grant nos.cx2019007 and cx2020047)the Basic and Frontier Research Project of Chongqing(grant no.CSTB2022NSCQ-MSX0320).
文摘We reported a new protocol for constructing a unique indolizine-containing perifused tricycle by combining a copper relay-catalyzed three-component cascade with a 12πelectrocyclization reaction from readily available starting materials.The indolizine generated by the copper-catalyzed multicomponent cascade is a key intermediate obtained during subsequent spontaneous electrocyclization.In contrast to the traditional SEAr reaction model,this study is based on the tetraene-like character of indolizine to form an aromatic heterocycle 12πelectron system that can spontaneously trigger 12πelectrocyclization.This transformation can not only enhance the reactivity of indolizine but also improve the electrocyclization model.This convergent strategy can significantly enhance synthetic versatility,and the resulting perifused cycle products containing indolizine may serve as a molecular platform for the discovery and characterization of pharmaceuticals and functional molecules.
