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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...

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Autores principales: Molven, Anders, Hollister-Lock, Jennifer, Hu, Jiang, Martinez, Rachael, Njølstad, Pål R., Liew, Chong Wee, Weir, Gordon, Kulkarni, Rohit N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2016
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.
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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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