Receptor-isoform-selective insulin analogues give tissue-preferential effects

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Standard

Receptor-isoform-selective insulin analogues give tissue-preferential effects. / Vienberg, Sara Gry; Bouman, Stephan D; Sørensen, Heidi; Stidsen, Carsten E; Kjeldsen, Thomas; Glendorf, Tine; Sørensen, Anders R; Olsen, Grith S; Andersen, Birgitte; Nishimura, Erica.

In: Biochemical Journal, Vol. 440, No. 3, 15.12.2011, p. 301-8.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Vienberg, SG, Bouman, SD, Sørensen, H, Stidsen, CE, Kjeldsen, T, Glendorf, T, Sørensen, AR, Olsen, GS, Andersen, B & Nishimura, E 2011, 'Receptor-isoform-selective insulin analogues give tissue-preferential effects', Biochemical Journal, vol. 440, no. 3, pp. 301-8. https://doi.org/10.1042/BJ20110880

APA

Vienberg, S. G., Bouman, S. D., Sørensen, H., Stidsen, C. E., Kjeldsen, T., Glendorf, T., Sørensen, A. R., Olsen, G. S., Andersen, B., & Nishimura, E. (2011). Receptor-isoform-selective insulin analogues give tissue-preferential effects. Biochemical Journal, 440(3), 301-8. https://doi.org/10.1042/BJ20110880

Vancouver

Vienberg SG, Bouman SD, Sørensen H, Stidsen CE, Kjeldsen T, Glendorf T et al. Receptor-isoform-selective insulin analogues give tissue-preferential effects. Biochemical Journal. 2011 Dec 15;440(3):301-8. https://doi.org/10.1042/BJ20110880

Author

Vienberg, Sara Gry ; Bouman, Stephan D ; Sørensen, Heidi ; Stidsen, Carsten E ; Kjeldsen, Thomas ; Glendorf, Tine ; Sørensen, Anders R ; Olsen, Grith S ; Andersen, Birgitte ; Nishimura, Erica. / Receptor-isoform-selective insulin analogues give tissue-preferential effects. In: Biochemical Journal. 2011 ; Vol. 440, No. 3. pp. 301-8.

Bibtex

@article{c64b983c807c4317b768b3ae04fa32ff,
title = "Receptor-isoform-selective insulin analogues give tissue-preferential effects",
abstract = "The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI) for inducing glycogen accumulation (75%) and lipogenesis (130%) than for affecting muscle (45%). For the same blood-glucose-lowering effect upon acute intravenous dosing of mice, INS-B gave a significantly higher degree of IR phosphorylation in liver than HI. These in vitro and in vivo results indicate that insulin analogues with IR-isoform-preferential binding affinity are able to elicit tissue-selective biological responses, depending on IR-A/IR-B expression.",
keywords = "Adipocytes, Adipose Tissue, Animals, Binding, Competitive, Blood Glucose, Brain, Cells, Cultured, Gene Expression, Glycogen, Hepatocytes, Humans, Hypoglycemic Agents, Insulin, Kidney, Lipogenesis, Liver, Male, Mice, Mice, Inbred C57BL, Muscle, Skeletal, Myocardium, Organ Specificity, Phosphorylation, Primary Cell Culture, Protein Isoforms, Rats, Rats, Sprague-Dawley, Receptor, Insulin, Spleen, Sus scrofa",
author = "Vienberg, {Sara Gry} and Bouman, {Stephan D} and Heidi S{\o}rensen and Stidsen, {Carsten E} and Thomas Kjeldsen and Tine Glendorf and S{\o}rensen, {Anders R} and Olsen, {Grith S} and Birgitte Andersen and Erica Nishimura",
year = "2011",
month = dec,
day = "15",
doi = "10.1042/BJ20110880",
language = "English",
volume = "440",
pages = "301--8",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - Receptor-isoform-selective insulin analogues give tissue-preferential effects

AU - Vienberg, Sara Gry

AU - Bouman, Stephan D

AU - Sørensen, Heidi

AU - Stidsen, Carsten E

AU - Kjeldsen, Thomas

AU - Glendorf, Tine

AU - Sørensen, Anders R

AU - Olsen, Grith S

AU - Andersen, Birgitte

AU - Nishimura, Erica

PY - 2011/12/15

Y1 - 2011/12/15

N2 - The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI) for inducing glycogen accumulation (75%) and lipogenesis (130%) than for affecting muscle (45%). For the same blood-glucose-lowering effect upon acute intravenous dosing of mice, INS-B gave a significantly higher degree of IR phosphorylation in liver than HI. These in vitro and in vivo results indicate that insulin analogues with IR-isoform-preferential binding affinity are able to elicit tissue-selective biological responses, depending on IR-A/IR-B expression.

AB - The relative expression patterns of the two IR (insulin receptor) isoforms, +/- exon 11 (IR-B/IR-A respectively), are tissue-dependent. Therefore we have developed insulin analogues with different binding affinities for the two isoforms to test whether tissue-preferential biological effects can be attained. In rats and mice, IR-B is the most prominent isoform in the liver (> 95%) and fat (> 90%), whereas in muscles IR-A is the dominant isoform (> 95%). As a consequence, the insulin analogue INS-A, which has a higher relative affinity for human IR-A, had a higher relative potency [compared with HI (human insulin)] for glycogen synthesis in rat muscle strips (26%) than for glycogen accumulation in rat hepatocytes (5%) and for lipogenesis in rat adipocytes (4%). In contrast, the INS-B analogue, which has an increased affinity for human IR-B, had higher relative potencies (compared with HI) for inducing glycogen accumulation (75%) and lipogenesis (130%) than for affecting muscle (45%). For the same blood-glucose-lowering effect upon acute intravenous dosing of mice, INS-B gave a significantly higher degree of IR phosphorylation in liver than HI. These in vitro and in vivo results indicate that insulin analogues with IR-isoform-preferential binding affinity are able to elicit tissue-selective biological responses, depending on IR-A/IR-B expression.

KW - Adipocytes

KW - Adipose Tissue

KW - Animals

KW - Binding, Competitive

KW - Blood Glucose

KW - Brain

KW - Cells, Cultured

KW - Gene Expression

KW - Glycogen

KW - Hepatocytes

KW - Humans

KW - Hypoglycemic Agents

KW - Insulin

KW - Kidney

KW - Lipogenesis

KW - Liver

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Muscle, Skeletal

KW - Myocardium

KW - Organ Specificity

KW - Phosphorylation

KW - Primary Cell Culture

KW - Protein Isoforms

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptor, Insulin

KW - Spleen

KW - Sus scrofa

U2 - 10.1042/BJ20110880

DO - 10.1042/BJ20110880

M3 - Journal article

C2 - 21851336

VL - 440

SP - 301

EP - 308

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

ER -

ID: 128935221