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

Finbarr O'Harte; AC Boyd; Aine McKillop; Yasser Abdel-Wahab; Helene McNulty; CR Barnett; JM Conlon; P Hojrup; Peter Flatt

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

Finbarr O'Harte, AC Boyd, Aine McKillop, Yasser Abdel-Wahab, Helene McNulty, CR Barnett, JM Conlon, P Hojrup, Peter Flatt

Research output: Contribution to journal › Article › peer-review

24 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.

Original language	English
Pages (from-to)	1519-1526
Journal	Peptides
Volume	21
Issue number	10
Publication status	Published (in print/issue) - Oct 2000

Cite this

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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",

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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

JO - Peptides

JF - Peptides

IS - 10

ER -

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

Abstract

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