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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Cell Physiol Biochem Press GmbH & Co KG
2017-11-01
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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 |
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