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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.
LanguageEnglish
Pages1519-1526
JournalPeptides
Volume21
Issue number10
Publication statusPublished - Oct 2000

Fingerprint

Hypoglycemic Agents
Insulin
Glucose
Abdominal Muscles
Glycogen
Digestion
Mass Spectrometry
High Pressure Liquid Chromatography

Cite this

@article{23afe966984746bbaa04ddbcdb8422b8,
title = "Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin",
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.",
author = "Finbarr O'Harte and AC Boyd and Aine McKillop and Yasser Abdel-Wahab and Helene McNulty and CR Barnett and JM Conlon and P Hojrup and Peter Flatt",
year = "2000",
month = "10",
language = "English",
volume = "21",
pages = "1519--1526",
number = "10",

}

Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin. / O'Harte, Finbarr; Boyd, AC; McKillop, Aine; Abdel-Wahab, Yasser; McNulty, Helene; Barnett, CR; Conlon, JM; Hojrup, P; Flatt, Peter.

Vol. 21, No. 10, 10.2000, p. 1519-1526.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin

AU - O'Harte, Finbarr

AU - Boyd, AC

AU - McKillop, Aine

AU - Abdel-Wahab, Yasser

AU - McNulty, Helene

AU - Barnett, CR

AU - Conlon, JM

AU - Hojrup, P

AU - Flatt, Peter

PY - 2000/10

Y1 - 2000/10

N2 - 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.

AB - 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.

M3 - Article

VL - 21

SP - 1519

EP - 1526

IS - 10

ER -