Navigation Links
Treatment corrects severe insulin imbalance in animal studies
Date:7/31/2008

Researchers have used a drug to achieve normal levels of blood sugar in animals genetically engineered to have abnormally high insulin levels. If this approach succeeds in humans, it could become an innovative medicine for children with congenital hyperinsulinism, a rare but potentially devastating genetic disease in which insulin levels become dangerously high.

"There is currently no effective medical treatment for children with the most common type of congenital hyperinsulinism," said study leader Diva D. De Len, M.D., a pediatric endocrinologist at The Children's Hospital of Philadelphia. "This type of congenital hyperinsulinism is caused by mutations in genes that encode important potassium channels in the pancreatic beta cells." The study team, from Children's Hospital and the University of Pennsylvania School of Medicine, published their report online on July 17 in the Journal of Biological Chemistry.

In congenital hyperinsulinism (HI), genetic mutations damage the insulin-secreting beta cells in the pancreas. Insulin levels rage out of control and severely reduce blood glucose, 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 somewhat higher incidence among certain groups, such as Ashkenazic Jews.

For the past 20 years, the standard medical treatment for some forms of HI has been the drug diazoxide, which controls insulin secretion by opening up crucial potassium channels in beta cells. However, this drug does not work in the most common and severe forms of HI, in which mutations prevent those channels from forming.

When the abnormal beta cells are confined to a discrete portion of the pancreas, as occurs in approximately half of HI cases, precise surgery on the tiny organ can remove the lesion and cure HI. The Children's Hospital of Philadelphia is a world leader in diagnosing such lesions and performing the curative surgery on newborns.

However, when abnormal cells are distributed throughout the pancreas in so-called diffuse HI, surgeons must remove nearly all the pancreas. This relieves HI in about a quarter of cases, but leaves the majority of patients at high risk for insulin imbalance, in which blood glucose levels are too low (hypoglycemia) or too high, resulting in diabetes.

The new study makes use of a peptide (an amino acid compound) called exendin-(9-39) that blocks the action of a specific hormone receptor in beta cells. Building on their previous work using exendin-(9-39) on normal mice, De Len's study team studied the peptide's effect on a strain of mice that had been genetically engineered to mimic the defect found in children with congenital HI.

When researchers withhold food from those mice, their blood glucose levels become low, a condition called fasting hypoglycemia. Mice who had received exendin-(9-39), however, had significantly higher levels of fasting blood glucose compared to mice that were not treated with the peptide, and reached levels comparable to those in normal, healthy animals. Further studies identified the mechanisms in the hormone signaling system that malfunctions in HI.

The next step, says De Len, is a pilot study now under way to test the effect of exendin-(9-39) in children and adults with congenital HI. If results from the pilot study are promising, her study team expects to progress to a larger clinical trial. "If this peptide can be developed into a treatment for children with this common form of HI, we may have a new tool for controlling their insulin levels and managing their disease," added De Len.

The Congenital Hyperinsulinism Center at Children's Hospital has worldwide prominence in diagnosing and treating this genetic disease. Much of its work builds on pioneering research by Charles A. Stanley, M.D., in identifying the specific gene defects that cause HI. Stanley is a co-author of the current study.


'/>"/>

Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6050
Children's Hospital of Philadelphia
Source:Eurekalert

Related biology news :

1. Video released of rapid Alzheimers improvement after new immune-based treatment
2. Fertility treatment in developing countries; a cycle of IVF for less than $200
3. New treatment approach promising for lymphoma patients in the developing world
4. Treatment delays result in poor outcomes for men with breast cancer
5. Counting tumor cells in blood predicts treatment benefit in prostate cancer
6. Stroke study reveals key target for improving treatment and suggests that Gleevec may help
7. Hypertension treatment effective in reversing vascular damage
8. Rong Li Lab identifies new role of inflammatory protein in PKD and a possible treatment
9. Source of drug-tolerant tuberculosis possibly behind TB relapses, intensity of treatment
10. Novel therapeutic strategy for colon cancer treatment
11. New ballast treatment could protect Great Lakes fish
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/3/2016)... , June 3, 2016 ... von Nepal hat ... Lieferung hochsicherer geprägter Kennzeichen, einschließlich Personalisierung, Registrierung ... in der Produktion und Implementierung von Identitätsmanagementlösungen. ... Ausschreibung im Januar teilgenommen, aber Decatur wurde ...
(Date:6/2/2016)... The Weather Company , an IBM Business (NYSE: IBM ... which consumers will be able to interact with IBM Watson ... or text and receive relevant information about the product or ... long sought an advertising solution that can create a one-to-one ... valuable; and can scale across millions of interactions and touchpoints. ...
(Date:6/1/2016)... , June 1, 2016 Favorable ... Election Administration and Criminal Identification to Boost Global Biometrics ... recently released TechSci Research report, " Global Biometrics Market ... Competition Forecast and Opportunities, 2011 - 2021", the global ... by 2021, on account of growing security concerns across ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... 2016 /PRNewswire/ - BIOREM Inc. (TSX-V: BRM) ("Biorem" or "the ... major shareholders, Clean Technology Fund I, LP and Clean ... based venture capital funds which together hold approximately ... fully diluted, as converted basis), that they have entered ... equity holdings in Biorem to TUS Holdings Co. Ltd. ...
(Date:6/27/2016)... ... June 27, 2016 , ... Parallel 6 , the ... today the Clinical Reach Virtual Patient Encounter CONSULT module which enables both ... physician and clinical trial team. , Using the CONSULT module, patients and physicians can ...
(Date:6/27/2016)... , June 27, 2016  Liquid Biotech ... the funding of a Sponsored Research Agreement with ... tumor cells (CTCs) from cancer patients.  The funding ... CTC levels correlate with clinical outcomes in cancer ... data will then be employed to support the ...
(Date:6/24/2016)... , June 24, 2016 Epic ... sensitively detects cancers susceptible to PARP inhibitors by ... tumor cells (CTCs). The new test has already ... therapeutics in multiple cancer types. Over ... DNA damage response pathways, including PARP, ATM, ATR, ...
Breaking Biology Technology: