EFFECT OF A HETEROBIVALENT GLUCAGON LIKE PEPTIDE-1 LINKED TO CHOLECYSTOKININ ON INSULIN SECRETION IN PANCREATIC β-CELLS

Persistent Link:
http://hdl.handle.net/10150/613295
Title:
EFFECT OF A HETEROBIVALENT GLUCAGON LIKE PEPTIDE-1 LINKED TO CHOLECYSTOKININ ON INSULIN SECRETION IN PANCREATIC β-CELLS
Author:
MOORE, COURTNEY MARIE
Issue Date:
2016
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
A goal of diabetes therapeutics is to deliver agents that target insulin secreting pancreaticβ-cells with high specificity while leaving other cells unaffected.Linking two ligands for two different receptors promotes binding to cells expressing the complementary receptors, thereby increasing the specificity for the target cells. Both Glucagon LikePeptide 1 (GLP-1) and Cholecystokinin (CCK) receptors are expressed on the surface of pancreatic β-cells. A ligand composed of GLP-1 linked to CCK-6 was produced and evaluated for its effect on β-cell insulin secretion. A combination of unlinked monomers activates insulin secretion at 100 nM in the absence of stimulatory glucose, an effect similar to CCK alone. However, the GLP-1/CCK-6 dimer potentiated glucose stimulated insulin secretin (GSIS) at low concentrations with higher sensitivity than the combined monomers.These findings suggest that the GLP-1 effect on GSIS(potentiation) is retained in the bivalent ligand, but the CCK effect may be attenuated or shifted in efficacy. The observed enhanced sensitivity to potentiate GSIS indicates that the binding affinity of the GLP-1/CCK-6 is increased via bivalent interactions as expected. Since bivalent binding requires the expression of both complementary receptors, this also suggests that the GLP-1/CCK-6 may have enhanced specificity for β-cells.
Type:
text; Electronic Thesis
Degree Name:
B.S.
Degree Level:
Bachelors
Degree Program:
Honors College; Biochemistry
Degree Grantor:
University of Arizona
Advisor:
Lynch, Ronald

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleEFFECT OF A HETEROBIVALENT GLUCAGON LIKE PEPTIDE-1 LINKED TO CHOLECYSTOKININ ON INSULIN SECRETION IN PANCREATIC β-CELLSen_US
dc.creatorMOORE, COURTNEY MARIEen
dc.contributor.authorMOORE, COURTNEY MARIEen
dc.date.issued2016-
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.abstractA goal of diabetes therapeutics is to deliver agents that target insulin secreting pancreaticβ-cells with high specificity while leaving other cells unaffected.Linking two ligands for two different receptors promotes binding to cells expressing the complementary receptors, thereby increasing the specificity for the target cells. Both Glucagon LikePeptide 1 (GLP-1) and Cholecystokinin (CCK) receptors are expressed on the surface of pancreatic β-cells. A ligand composed of GLP-1 linked to CCK-6 was produced and evaluated for its effect on β-cell insulin secretion. A combination of unlinked monomers activates insulin secretion at 100 nM in the absence of stimulatory glucose, an effect similar to CCK alone. However, the GLP-1/CCK-6 dimer potentiated glucose stimulated insulin secretin (GSIS) at low concentrations with higher sensitivity than the combined monomers.These findings suggest that the GLP-1 effect on GSIS(potentiation) is retained in the bivalent ligand, but the CCK effect may be attenuated or shifted in efficacy. The observed enhanced sensitivity to potentiate GSIS indicates that the binding affinity of the GLP-1/CCK-6 is increased via bivalent interactions as expected. Since bivalent binding requires the expression of both complementary receptors, this also suggests that the GLP-1/CCK-6 may have enhanced specificity for β-cells.en
dc.typetexten
dc.typeElectronic Thesisen
thesis.degree.nameB.S.en
thesis.degree.levelBachelorsen
thesis.degree.disciplineHonors Collegeen
thesis.degree.disciplineBiochemistryen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorLynch, Ronalden
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