The purpose of this study is to determine if Exendin-(9-39), an antagonist of the
glucagon-like peptide-1 (GLP-1) receptor with effects on the pancreatic beta cell, increases
fasting blood glucose levels in subjects with congenital hyperinsulinism.
This is an open-label, pilot study , to determine if Exendin-(9-39), an antagonist of the
glucagon-like peptide-1 (GLP-1) receptor with effects on the pancreatic beta cells, increases
fasting blood glucose levels in subjects with congenital hyperinsulinism. Our overall
hypothesis is that abnormal GLP-1 secretion resulting from dysfunctional nutrient sensing in
intestinal L-cells plays a role in the dysregulated insulin secretion characteristic of this
disorder, and that antagonism of the GLP-1 receptor will increase fasting blood glucose
Aim 1. To evaluate the dose of exendin-(9-39) required to elevate fasting blood glucose
levels in subjects with congenital hyperinsulinism due to KATP channel mutations.
Aim 2. To determine therapeutic plasma levels, plasma half-life and pharmacokinetics of
exendin-(9-39) during an intravenous short-term infusion in subjects with congenital
hyperinsulinism due to Adenosine triphosphate (ATP)-sensitive potassium channel (KATP)
- Subjects with congenital hyperinsulinism
- Acute medical illness
- History of other systemic chronic disease such as cardiac failure, renal
insufficiency, hepatic insufficiency, chronic obstructive pulmonary disease, anemia,
or uncontrolled hypertension
- Diabetes mellitus
- Use of medications that affect glucose metabolism, such as glucocorticoids, beta
agonists, diazoxide and octreotide.
- Subjects will be eligible to participate 48 hrs after the last dose of octreotide and
72 hrs after last dose of diazoxide