Journal
DIABETES
Volume 61, Issue 10, Pages 2585-2591Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db12-0166
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Funding
- National Institutes of Health [1R03DK078535]
- Lester and Liesel Baker Foundation
- Clifford and Katherine Goldsmith Foundation
- National Center for Research Resources [UL1RR024134]
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Infants with congenital hyperinsulinism owing to inactivating mutations in the K-ATP channel (KATPHI) who are unresponsive to medical therapy will require pancreatectomy to control the hypoglycemia. In preclinical studies, we showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1(-/-) mice. The aim of this study was to examine the effects of exendin-(9-39) on fasting blood glucose in subjects with KATPHI. This was a randomized, open-label, two-period crossover pilot clinical study. Nine subjects with KATPHI received either exendin-(9-39) or vehicle on two different days. The primary outcome was blood glucose; secondary outcomes were insulin, glucagon, and GLP-1. In all subjects, mean nadir blood glucose and glucose area under the curve were significantly increased by exendin-(9-39). Insulin-to-glucose ratios were significantly lower during exendin-(9-39) infusion compared with vehicle. Fasting glucagon and intact GLP-1 were not affected by treatment. In addition, exendin-(9-39) significantly inhibited amino acid-stimulated insulin secretion in pancreatic islets isolated from neonates with KATPHI Our findings have two important implications: 1) GLP-1 and its receptor play a role in the regulation of fasting glycemia in KATPHI; and 2) the GLP-1 receptor may be a therapeutic target for the treatment of children with KATPHI. Diabetes 61:2585-2591, 2012
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