In pilot study, a peptide controls blood sugar in people with congenital hyperinsulinism

August 1, 2012

A pilot study in adolescents and adults has found that an investigational drug shows promise as the first potential medical treatment for children with the severest type of congenital hyperinsulinism, a rare but potentially devastating disease in which gene mutations cause insulin levels to become dangerously high.

"There is currently no effective medicine for children with the most common and most severe form of hyperinsulinism," said study leader Diva D. De Leon, M.D., a pediatric endocrinologist at The Children's Hospital of Philadelphia. "Our new research shows that this investigational drug, a peptide called exendin-(9-39), controls in people, a very promising result."

The study appeared today online ahead of print in the journal Diabetes.

In congenital hyperinsulinism (HI), mutations disrupt the insulin-secreting in the pancreas. Uncontrolled, excessive thus sharply reduce , a condition called hypoglycemia. If untreated, hypoglycemia may cause irreversible brain damage or death in children. Congenital HI occurs in an estimated one in 50,000 U.S. children, with a higher incidence among Ashkenazic Jews and certain other groups.

The standard treatment for some forms of congenital HI is diazoxide, a drug that controls insulin secretion by opening in beta cells. However, this drug does not work in the most common types of HI, in which mutations prevent these potassium channels from forming.

When abnormal beta cells occur only in a discrete portion of the pancreas, precise surgery on the tiny organ can remove the lesion and cure HI. The Congenital Hyperinsulinism Center at The Children's Hospital of Philadelphia is a world leader in diagnosing such lesions and performing the curative surgery on newborns.

However, in roughly half of congenital HI cases, are diffused through the pancreas, and surgeons must remove nearly the entire pancreas. This leaves the majority of patients at high risk of developing diabetes.

The current study, which builds on previous research by De Leon and colleagues in animals, uses exendin-(9-39), which blocks the action of a hormone receptor, glucagon-like peptide-1 (GLP-1), in beta cells. The GLP-1 receptor is currently the target of drugs that treat diabetes, using the opposite effect from that investigated in this HI study.

The current pilot study included nine subjects, aged 15 to 47 years old, who had hyperinsulinism caused by mutations in potassium channels. None were being treated for HI at the time of the study, but all were at risk of hypoglycemia during periods of fasting.

In all nine subjects, the drug controlled blood glucose levels during fasting. Exendin also controlled in cell studies of beta cells taken from newborns with HI. The current research did not focus on the biological mechanisms that occurred, but De Leon said the results are encouraging enough to progress to a clinical study in children with HI over the next year.

Explore further: Animal study suggests that newborn period may be crucial time to prevent later diabetes

More information: "The GLP-1 Receptor Antagonist Exendin-(9-39) Elevates Blood Fasting Glucose Levels in Congenital Hyperinsulinism due to Inactivating Mutations in the ATP-sensitive Potassium Channel," Diabetes, published online Aug.1, 2012, to appear in print, October 2012. doi: 10.2337/db12-0166

Related Stories

Animal study suggests that newborn period may be crucial time to prevent later diabetes

November 2, 2011
Pediatric researchers who tested newborn animals with an existing human drug used in adults with diabetes report that this drug, when given very early in life, prevents diabetes from developing in adult animals. If this finding ...

Insulin signaling is distorted in pancreases of Type 2 diabetics

December 13, 2011
Insulin signaling is altered in the pancreas, a new study shows for the first time in humans. The errant signals disrupt both the number and quality of beta cells — the cells that produce insulin.

Recommended for you

Getting fat to 'talk' again could lower blood glucose and weight

August 22, 2017
Diabetes is a tough disease to manage. Oral medications, insulin shots, close monitoring of blood sugar, dietary changes and exercise can all factor into a person's treatment regimen. Now researchers are exploring a novel, ...

Biochemical 'fingerprints' reveal diabetes progression

August 21, 2017
Researchers from Umeå University in Sweden describe a new method to study biochemical changes that occur in the pancreas during the development of diabetes. The method, recently published in Scientific Reports, is based ...

In a nutshell: Walnuts activate brain region involved in appetite control

August 17, 2017
Packed with nutrients linked to better health, walnuts are also thought to discourage overeating by promoting feelings of fullness. Now, in a new brain imaging study, researchers at Beth Israel Deaconess Medical Center (BIDMC) ...

Smart mat detects early warning signs of foot ulcers

August 16, 2017
While completing his residency in anesthesiology at Massachusetts General Hospital in the mid-2000s, Jon Bloom saw his fair share of foot amputations among patients with diabetes. The culprit: infected foot ulcers.

The best place to treat type 1 diabetes might be just under your skin

August 14, 2017
A group of U of T researchers have demonstrated that the space under our skin might be an optimal location to treat type 1 diabetes (T1D).

New measure of insulin-making cells could gauge diabetes progression, treatment

August 10, 2017
Researchers at the University of Wisconsin-Madison have developed a new measurement for the volume and activity of beta cells, the source of the sugar-regulating hormone insulin.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.