• Fasting blood glucose level [ Time Frame: 7 hours ] [ Designated as safety issue: No ]
  

• Insulin, glucagon-like peptide-1 and insulin levels [ Time Frame: 7 hours ] [ Designated as safety issue: No ]
  

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 levels.

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 KATP channel mutations.

Inclusion Criteria:

• Subjects with congenital hyperinsulinism

Exclusion Criteria:

• 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
• Pregnancy
• 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