Glucagon-like peptide-1 (GLP-1) has been shown to be the most potent naturally occurring incretin (hormone released from the gut after food ingestion) with respect to its ability to stimulate insulin release in both non-diabetic and type 2 diabetic volunteers. In addition to the well-established effect on insulin release, GLP-1 has also been shown to stimulate insulin synthesis, increase mRNA for glucokinase, inhibit gastric emptying and regulate appetite. All of these effects lead to an improvement in glucose homeostasis as demonstrated by a reduction in HbA1c. A major advantage of this peptide is that it is a naturally occurring hormone with all the benefits outlined above. The major disadvantage is that the half-life of the peptide in blood is in the order of 2-8 minutes. Thus, it is necessary to either administer this hormone in a continuous manner or several times per day. This has resulted in a major effort by the pharmaceutical industry to look for a substance that has a great deal of homology, and therefore, by inference, action to GLP-1, but with a far longer duration of action. Several substances have been identified either through substitution of regulatory amino acids in the GLP-1 sequence or by identification of peptides in other species which mimic GLP-1's actions. A very potent agent originally isolated from Heloderma Suspectum saliva, named Exendin-4, ahs been shown to fulfill the desired effect. E-4 has been shown in a variety of animal models, including the Rhesus monkey, to lower glucose at least in part through its insulinotropic effect.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR002719-15
Application #
6408473
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
1985-12-01
Project End
2002-11-30
Budget Start
Budget End
Support Year
15
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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