Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity

Background/Aims: Rodent islets are often used for basic science research but they do not always recapitulate signalling events in human islets. This study evaluated the glucose-dependent responses of human and mouse islets in terms of dynamic insulin secretion, metabolic coupling and the role of glu...

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Main Authors: Attilio Pingitore, Inmaculada Ruz-Maldonado, Bo Liu, Guo Cai Huang, Pratik Choudhary, Shanta J. Persaud
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2017-11-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:https://www.karger.com/Article/FullText/485532
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spelling doaj-2560955b340a491bb1324654da86b8e82020-11-25T01:00:16ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-11-014441352135910.1159/000485532485532Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose SensitivityAttilio PingitoreInmaculada Ruz-MaldonadoBo LiuGuo Cai HuangPratik ChoudharyShanta J. PersaudBackground/Aims: Rodent islets are often used for basic science research but they do not always recapitulate signalling events in human islets. This study evaluated the glucose-dependent responses of human and mouse islets in terms of dynamic insulin secretion, metabolic coupling and the role of glucose transporters. Methods: Glucose-induced insulin secretion from isolated mouse and human islets was profiled by perifusion and islet ATP levels were measured by chemoluminescence assay. Glucose transporter expression was determined by qPCR and western blotting. Results: Human islets show a left-shifted glucose concentration-insulin secretion profile compared to mouse islets. These data are consistent with glucose transporter expression, with human islets expressing mainly GLUT1 and GLUT3, and GLUT2 being the predominant transporter in mouse islets. Using the GLUT1 inhibitor STF-31 we unveiled an important role for GLUT1 for differences in glucose-induced insulin secretion profiles observed between the two species. Conclusion: The high affinity of GLUT1/3 for glucose reflects the left-shifted glucose-induced insulin secretory response of human islets and the impairment of insulin secretion from human islets after STF-31 treatment indicates an important role for GLUT1 in human islet stimulus-secretion coupling. Our data provide further insight into key differences between insulin secretion regulation in mouse and human islets.https://www.karger.com/Article/FullText/485532Islets of LangerhansInsulin secretionATP generationGlucose transportersMetabolic couplingGLUT1
collection DOAJ
language English
format Article
sources DOAJ
author Attilio Pingitore
Inmaculada Ruz-Maldonado
Bo Liu
Guo Cai Huang
Pratik Choudhary
Shanta J. Persaud
spellingShingle Attilio Pingitore
Inmaculada Ruz-Maldonado
Bo Liu
Guo Cai Huang
Pratik Choudhary
Shanta J. Persaud
Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity
Cellular Physiology and Biochemistry
Islets of Langerhans
Insulin secretion
ATP generation
Glucose transporters
Metabolic coupling
GLUT1
author_facet Attilio Pingitore
Inmaculada Ruz-Maldonado
Bo Liu
Guo Cai Huang
Pratik Choudhary
Shanta J. Persaud
author_sort Attilio Pingitore
title Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity
title_short Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity
title_full Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity
title_fullStr Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity
title_full_unstemmed Dynamic Profiling of Insulin Secretion and ATP Generation in Isolated Human and Mouse Islets Reveals Differential Glucose Sensitivity
title_sort dynamic profiling of insulin secretion and atp generation in isolated human and mouse islets reveals differential glucose sensitivity
publisher Cell Physiol Biochem Press GmbH & Co KG
series Cellular Physiology and Biochemistry
issn 1015-8987
1421-9778
publishDate 2017-11-01
description Background/Aims: Rodent islets are often used for basic science research but they do not always recapitulate signalling events in human islets. This study evaluated the glucose-dependent responses of human and mouse islets in terms of dynamic insulin secretion, metabolic coupling and the role of glucose transporters. Methods: Glucose-induced insulin secretion from isolated mouse and human islets was profiled by perifusion and islet ATP levels were measured by chemoluminescence assay. Glucose transporter expression was determined by qPCR and western blotting. Results: Human islets show a left-shifted glucose concentration-insulin secretion profile compared to mouse islets. These data are consistent with glucose transporter expression, with human islets expressing mainly GLUT1 and GLUT3, and GLUT2 being the predominant transporter in mouse islets. Using the GLUT1 inhibitor STF-31 we unveiled an important role for GLUT1 for differences in glucose-induced insulin secretion profiles observed between the two species. Conclusion: The high affinity of GLUT1/3 for glucose reflects the left-shifted glucose-induced insulin secretory response of human islets and the impairment of insulin secretion from human islets after STF-31 treatment indicates an important role for GLUT1 in human islet stimulus-secretion coupling. Our data provide further insight into key differences between insulin secretion regulation in mouse and human islets.
topic Islets of Langerhans
Insulin secretion
ATP generation
Glucose transporters
Metabolic coupling
GLUT1
url https://www.karger.com/Article/FullText/485532
work_keys_str_mv AT attiliopingitore dynamicprofilingofinsulinsecretionandatpgenerationinisolatedhumanandmouseisletsrevealsdifferentialglucosesensitivity
AT inmaculadaruzmaldonado dynamicprofilingofinsulinsecretionandatpgenerationinisolatedhumanandmouseisletsrevealsdifferentialglucosesensitivity
AT boliu dynamicprofilingofinsulinsecretionandatpgenerationinisolatedhumanandmouseisletsrevealsdifferentialglucosesensitivity
AT guocaihuang dynamicprofilingofinsulinsecretionandatpgenerationinisolatedhumanandmouseisletsrevealsdifferentialglucosesensitivity
AT pratikchoudhary dynamicprofilingofinsulinsecretionandatpgenerationinisolatedhumanandmouseisletsrevealsdifferentialglucosesensitivity
AT shantajpersaud dynamicprofilingofinsulinsecretionandatpgenerationinisolatedhumanandmouseisletsrevealsdifferentialglucosesensitivity
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