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Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin

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

O'Harte, Finbarr, Boyd, AC, McKillop, Aine, Abdel-Wahab, Yasser, McNulty, Helene, Barnett, CR, Conlon, JM, Hojrup, P and Flatt, Peter (2000) Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin. PEPTIDES, 21 (10). pp. 1519-1526. [Journal article]

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Abstract

Human insulin was glycated under hyperglycemic reducing conditions and a novel diglycated form (M-r 6135.1 Da) was purified by RP-HPLC. Endoproteinase Glu-C digestion combined with mass spectrometry and automated Edman degradation localized glycation to Gly(1) and Phe(1) of the insulin A- and B-chains, respectively. Intraperitoneal (i.p.) administration of diglycated insulin to mice alone or in combination with glucose (7 nmol/kg) resulted in a 43-61% and 11-34% reduction in glucose lowering activity, respectively, compared with native insulin. Consistent with these findings, diglycated insulin (10(-9) to 10(-7) mol/liter) was 22-38% less effective (P < 0.001) than native insulin in stimulating glucose uptake, glucose oxidation and glycogen production in isolated mouse abdominal muscle. (C) 2000 Elsevier Science Inc. All rights reserved.

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:3088
Deposited By:Professor Peter Flatt
Deposited On:13 Jan 2010 21:12
Last Modified:28 Feb 2011 11:23

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