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The Hypoglycemic Phenotype Is Islet Cell–Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase–Deficient Mice
Congenital hyperinsulinism of infancy (CHI) can be caused by inactivating mutations in the gene encoding short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), a ubiquitously expressed enzyme involved in fatty acid oxidation. The hypersecretion of insulin may be explained by a loss of interaction betw...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878426/ https://www.ncbi.nlm.nih.gov/pubmed/26953163 http://dx.doi.org/10.2337/db15-1475 |
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author | Molven, Anders Hollister-Lock, Jennifer Hu, Jiang Martinez, Rachael Njølstad, Pål R. Liew, Chong Wee Weir, Gordon Kulkarni, Rohit N. |
author_facet | Molven, Anders Hollister-Lock, Jennifer Hu, Jiang Martinez, Rachael Njølstad, Pål R. Liew, Chong Wee Weir, Gordon Kulkarni, Rohit N. |
author_sort | Molven, Anders |
collection | PubMed |
description | Congenital hyperinsulinism of infancy (CHI) can be caused by inactivating mutations in the gene encoding short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), a ubiquitously expressed enzyme involved in fatty acid oxidation. The hypersecretion of insulin may be explained by a loss of interaction between SCHAD and glutamate dehydrogenase in the pancreatic β-cells. However, there is also a general accumulation of metabolites specific for the enzymatic defect in affected individuals. It remains to be explored whether hypoglycemia in SCHAD CHI can be uncoupled from the systemic effect on fatty acid oxidation. We therefore transplanted islets from global SCHAD knockout (SCHADKO) mice into mice with streptozotocin-induced diabetes. After transplantation, SCHADKO islet recipients exhibited significantly lower random and fasting blood glucose compared with mice transplanted with normal islets or nondiabetic, nontransplanted controls. Furthermore, intraperitoneal glucose tolerance was improved in animals receiving SCHADKO islets compared with those receiving normal islets. Graft β-cell proliferation and apoptosis rates were similar in the two transplantation groups. We conclude that hypoglycemia in SCHAD-CHI is islet cell–autonomous. |
format | Online Article Text |
id | pubmed-4878426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-48784262017-06-01 The Hypoglycemic Phenotype Is Islet Cell–Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase–Deficient Mice Molven, Anders Hollister-Lock, Jennifer Hu, Jiang Martinez, Rachael Njølstad, Pål R. Liew, Chong Wee Weir, Gordon Kulkarni, Rohit N. Diabetes Islet Studies Congenital hyperinsulinism of infancy (CHI) can be caused by inactivating mutations in the gene encoding short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), a ubiquitously expressed enzyme involved in fatty acid oxidation. The hypersecretion of insulin may be explained by a loss of interaction between SCHAD and glutamate dehydrogenase in the pancreatic β-cells. However, there is also a general accumulation of metabolites specific for the enzymatic defect in affected individuals. It remains to be explored whether hypoglycemia in SCHAD CHI can be uncoupled from the systemic effect on fatty acid oxidation. We therefore transplanted islets from global SCHAD knockout (SCHADKO) mice into mice with streptozotocin-induced diabetes. After transplantation, SCHADKO islet recipients exhibited significantly lower random and fasting blood glucose compared with mice transplanted with normal islets or nondiabetic, nontransplanted controls. Furthermore, intraperitoneal glucose tolerance was improved in animals receiving SCHADKO islets compared with those receiving normal islets. Graft β-cell proliferation and apoptosis rates were similar in the two transplantation groups. We conclude that hypoglycemia in SCHAD-CHI is islet cell–autonomous. American Diabetes Association 2016-06 2016-03-07 /pmc/articles/PMC4878426/ /pubmed/26953163 http://dx.doi.org/10.2337/db15-1475 Text en © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
spellingShingle | Islet Studies Molven, Anders Hollister-Lock, Jennifer Hu, Jiang Martinez, Rachael Njølstad, Pål R. Liew, Chong Wee Weir, Gordon Kulkarni, Rohit N. The Hypoglycemic Phenotype Is Islet Cell–Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase–Deficient Mice |
title | The Hypoglycemic Phenotype Is Islet Cell–Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase–Deficient Mice |
title_full | The Hypoglycemic Phenotype Is Islet Cell–Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase–Deficient Mice |
title_fullStr | The Hypoglycemic Phenotype Is Islet Cell–Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase–Deficient Mice |
title_full_unstemmed | The Hypoglycemic Phenotype Is Islet Cell–Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase–Deficient Mice |
title_short | The Hypoglycemic Phenotype Is Islet Cell–Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase–Deficient Mice |
title_sort | hypoglycemic phenotype is islet cell–autonomous in short-chain hydroxyacyl-coa dehydrogenase–deficient mice |
topic | Islet Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878426/ https://www.ncbi.nlm.nih.gov/pubmed/26953163 http://dx.doi.org/10.2337/db15-1475 |
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