Journal
DIABETES
Volume 65, Issue 6, Pages 1672-1678Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db15-1475
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Funding
- Fulbright fellowship
- Novo Nordisk Foundation [NNF150C0016330]
- Western Norway Regional Health Authority
- KG Jebsen Foundation
- Research Council of Norway (Norges Forskningsrad) [FRIMEDBIO 240788]
- European Research Council
- National Institutes of Health [K99-DK-090210, R01-DK-67536, R01-DK-103215]
- Novo Nordisk Fonden [NNF14OC0010659, NNF15OC0016330] Funding Source: researchfish
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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 beta-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 beta-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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