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

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2000-Oct
OriginalsprogEngelsk
TidsskriftPeptides
Vol/bind21
Udgave nummer10
Sider (fra-til)1519-26
Antal sider7
ISSN0196-9781
DOI
StatusUdgivet - 1. okt. 2000

Fingeraftryk

Hypoglycemic Agents
Insulin
Glucose
Abdominal Muscles
Glycogen
Mass spectrometry
Muscle
High Pressure Liquid Chromatography
Degradation
Oxidation

Citer dette

O'Harte, F. P., Boyd, A. C., McKillop, A. M., Abdel-Wahab, Y. H., McNulty, H., Barnett, C. R., ... Flatt, P. R. (2000). Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin. Peptides, 21(10), 1519-26. https://doi.org/10.1016/S0196-9781(00)00306-5
O'Harte, F P ; Boyd, A C ; McKillop, A M ; Abdel-Wahab, Y H ; McNulty, H ; Barnett, C R ; Conlon, J M ; Højrup, P ; Flatt, P R. / Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin. I: Peptides. 2000 ; Bind 21, Nr. 10. s. 1519-26.
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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.",
keywords = "Amino Acids, Animals, Biological Transport, Blood Glucose, Chromatography, High Pressure Liquid, Deoxyglucose, Glucose, Glycogen, Glycoproteins, Glycosylation, Humans, Hyperglycemia, Injections, Intraperitoneal, Insulin, Male, Mass Spectrometry, Mice, Mice, Inbred Strains, Muscle, Smooth, Serine Endopeptidases",
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O'Harte, FP, Boyd, AC, McKillop, AM, Abdel-Wahab, YH, McNulty, H, Barnett, CR, Conlon, JM, Højrup, P & Flatt, PR 2000, 'Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin.', Peptides, bind 21, nr. 10, s. 1519-26. https://doi.org/10.1016/S0196-9781(00)00306-5

Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin. / O'Harte, F P; Boyd, A C; McKillop, A M; Abdel-Wahab, Y H; McNulty, H; Barnett, C R; Conlon, J M; Højrup, P; Flatt, P R.

I: Peptides, Bind 21, Nr. 10, 01.10.2000, s. 1519-26.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

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

AU - O'Harte, F P

AU - Boyd, A C

AU - McKillop, A M

AU - Abdel-Wahab, Y H

AU - McNulty, H

AU - Barnett, C R

AU - Conlon, J M

AU - Højrup, P

AU - Flatt, P R

PY - 2000/10/1

Y1 - 2000/10/1

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.

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.

KW - Amino Acids

KW - Animals

KW - Biological Transport

KW - Blood Glucose

KW - Chromatography, High Pressure Liquid

KW - Deoxyglucose

KW - Glucose

KW - Glycogen

KW - Glycoproteins

KW - Glycosylation

KW - Humans

KW - Hyperglycemia

KW - Injections, Intraperitoneal

KW - Insulin

KW - Male

KW - Mass Spectrometry

KW - Mice

KW - Mice, Inbred Strains

KW - Muscle, Smooth

KW - Serine Endopeptidases

U2 - 10.1016/S0196-9781(00)00306-5

DO - 10.1016/S0196-9781(00)00306-5

M3 - Journal article

VL - 21

SP - 1519

EP - 1526

JO - Peptides

JF - Peptides

SN - 0196-9781

IS - 10

ER -

O'Harte FP, Boyd AC, McKillop AM, Abdel-Wahab YH, McNulty H, Barnett CR et al. Structure, antihyperglycemic activity and cellular actions of a novel diglycated human insulin. Peptides. 2000 okt 1;21(10):1519-26. https://doi.org/10.1016/S0196-9781(00)00306-5