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Diabetes. 2016 Jun;65(6):1672-8. doi: 10.2337/db15-1475. Epub 2016 Mar 7.

The Hypoglycemic Phenotype Is Islet Cell-Autonomous in Short-Chain Hydroxyacyl-CoA Dehydrogenase-Deficient Mice.

Author information

1
Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway Department of Pathology, Haukeland University Hospital, Bergen, Norway anders.molven@uib.no.
2
Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA.
3
KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
4
Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL.
5
Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Harvard Stem Cell Institute, Boston, MA.

Abstract

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.

PMID:
26953163
PMCID:
PMC4878426
DOI:
10.2337/db15-1475
[Indexed for MEDLINE]
Free PMC Article

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