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NMR and alanine scan studies of glucose-dependent insulinotropic polypeptide in water

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Alana, I, Parker, JC, Gault, Victor, Flatt, Peter, O'Harte, Finbarr, Malthouse, JPG and Hewage, CM (2006) NMR and alanine scan studies of glucose-dependent insulinotropic polypeptide in water. JOURNAL OF BIOLOGICAL CHEMISTRY, 281 (24). pp. 16370-16376. [Journal article]

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DOI: 10.1074/jbc.M510414200

Abstract

Glucose-dependent insulinotropic polypeptide ( GIP) is an incretin hormone that stimulates the secretion of insulin after ingestion of food. GIP also promotes the synthesis of fatty acids in adipose tissue. Therefore, it is not surprising that numerous literature reports have shown that GIP is linked to diabetes and obesity-related diseases. In this study, we present the solution structure of GIP in water determined by NMR spectroscopy. The calculated structure is characterized by the presence of an alpha-helical motif between residues Ser11 and Gln29. The helical conformation of GIP is further supported by CD spectroscopic studies. Six GIP-( 1-42) Ala(1-7) analogues were synthesized by replacing individual N-terminal residues with alanine. Alanine scan studies of these N-terminal residues showed that the GIP-( 1-42) Ala(6) was the only analogue to show insulin-secreting activity similar to that of the native GIP. However, when compared with glucose, its insulinotropic ability was reduced. For the first time, these NMR and modeling results contribute to the understanding of the structural requirements for the biological activity of GIP.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2980
Deposited By:Professor Peter Flatt
Deposited On:18 Dec 2009 09:22
Last Modified:11 Jun 2010 09:44

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