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

F. P.M. O'Harte; A. C. Boyd; A. M. McKillop; Y. H.A. Abdel-Wahab; H. McNulty; C. R. Barnett; J. M. Conlon; P. Hojrup; P. R. Flatt

doi:10.1016/S0196-9781(00)00306-5

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

F. P.M. O'Harte, A. C. Boyd, A. M. McKillop, Y. H.A. Abdel-Wahab, H. McNulty, C. R. Barnett, J. M. Conlon, P. Hojrup, P. R. 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 Gly¹ and Phe¹ 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. Copyright (C) 2000 Elsevier Science Inc.

Original language	English
Pages (from-to)	1519-1526
Number of pages	8
Journal	Peptides
Volume	21
Issue number	10
DOIs	https://doi.org/10.1016/S0196-9781(00)00306-5
Publication status	Published - 2000
Externally published	Yes

Keywords

Diglycated insulin
Glucose homeostasis
Glucose transport and metabolism
Glycation
Insulin
Mass spectrometry

ASJC Scopus subject areas

Biochemistry
Physiology
Endocrinology
Cellular and Molecular Neuroscience

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10.1016/S0196-9781(00)00306-5

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 Gly1 and Phe1 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. Copyright (C) 2000 Elsevier Science Inc.",

keywords = "Diglycated insulin, Glucose homeostasis, Glucose transport and metabolism, Glycation, Insulin, Mass spectrometry",

author = "O'Harte, {F. P.M.} and Boyd, {A. C.} and McKillop, {A. M.} and Abdel-Wahab, {Y. H.A.} and H. McNulty and Barnett, {C. R.} and Conlon, {J. M.} and P. Hojrup and Flatt, {P. R.}",

year = "2000",

doi = "10.1016/S0196-9781(00)00306-5",

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volume = "21",

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

AU - O'Harte, F. P.M.

AU - Boyd, A. C.

AU - McKillop, A. M.

AU - Abdel-Wahab, Y. H.A.

AU - McNulty, H.

AU - Barnett, C. R.

AU - Conlon, J. M.

AU - Hojrup, P.

AU - Flatt, P. R.

PY - 2000

Y1 - 2000

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 Gly1 and Phe1 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. Copyright (C) 2000 Elsevier Science Inc.

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 Gly1 and Phe1 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. Copyright (C) 2000 Elsevier Science Inc.

KW - Diglycated insulin

KW - Glucose homeostasis

KW - Glucose transport and metabolism

KW - Glycation

KW - Insulin

KW - Mass spectrometry

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AN - SCOPUS:0033786581

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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