Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes

M Gejl; H M Søndergaard; Chalotte Willemann Stecher; Bo Martin Bibby; N Møller; H E Bøtker; S B Hansen; Albert Gjedde; Jørgen Rungby; B Brock

doi:10.1210/jc.2011-3456

Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes

M Gejl, H M Søndergaard, Chalotte Willemann Stecher, Bo Martin Bibby, N Møller, H E Bøtker, S B Hansen, Albert Gjedde, Jørgen Rungby, B Brock

Eyepath Lab

50 Citationer (Scopus)

Abstract

Context: Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists provide beneficial cardiovascular effects by protecting against ischemia and reperfusion injury. Type 2 diabetes mellitus patients have reduced glycolysis in the heart. Objective: We hypothesized that cardioprotection by GLP-1 is achieved through increased glucose availability and utilization and aimed to assess the effect of exenatide, a synthetic GLP-1 receptor agonist, on myocardial glucose uptake (MGU), myocardial glucose transport, and myocardial blood flow (MBF). Design and Methods: We conducted a randomized, double-blinded, placebo-controlled crossover study in eight male, insulin-naive, type 2 diabetes mellitus patients without coronary artery disease. Positron emission tomography was used to determine the effect of exenatide on MGU and MBF during a pituitary-pancreatic hyperglycemic clamp with ¹⁸F-fluorodeoxyglucose and ¹³N-ammonia as tracers. Results: Overall, exenatide did not alter MGU. However, regression analysis revealed that exenatide altered initial clearance of glucose over the membrane of cardiomyocytes and MGU, depending on the level of insulin resistance (P±0.017 and 0.010, respectively). Exenatide increased MBF from 0.73 ± 0.094 to 0.85 ± 0.091 ml/g ± min (P ± 0.0056). Except for an increase in C-peptide levels, no differences in circulating hormones or metabolites were found. Conclusions: The action of exenatide as an activator or inhibitor of the glucose transport and glucose uptake in cardiomyocytes is dependentonbaseline activity of glucose transport and insulin resistance. Exenatide increases MBF without changing MGU.

Originalsprog	Engelsk
Tidsskrift	The Journal of clinical endocrinology and metabolism
Vol/bind	97
Udgave nummer	7
Sider (fra-til)	E1165-9
Antal sider	5
ISSN	0021-972X
DOI	https://doi.org/10.1210/jc.2011-3456
Status	Udgivet - jul. 2012

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10.1210/jc.2011-3456

https://academic.oup.com/jcem/article-pdf/97/7/E1165/10781639/jcem1165.pdf

Citationsformater

Gejl, M., Søndergaard, H. M., Stecher, C. W., Bibby, B. M., Møller, N., Bøtker, H. E., Hansen, S. B., Gjedde, A., Rungby, J., & Brock, B. (2012). Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes. The Journal of clinical endocrinology and metabolism, 97(7), E1165-9. https://doi.org/10.1210/jc.2011-3456

Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes. / Gejl, M; Søndergaard, H M; Stecher, Chalotte Willemann et al.

I: The Journal of clinical endocrinology and metabolism, Bind 97, Nr. 7, 07.2012, s. E1165-9.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Gejl, M, Søndergaard, HM, Stecher, CW, Bibby, BM, Møller, N, Bøtker, HE, Hansen, SB, Gjedde, A, Rungby, J & Brock, B 2012, 'Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes', The Journal of clinical endocrinology and metabolism, bind 97, nr. 7, s. E1165-9. https://doi.org/10.1210/jc.2011-3456

@article{a7ad41666b55486fa829d82c2358d1d0,

title = "Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes",

abstract = "Context: Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists provide beneficial cardiovascular effects by protecting against ischemia and reperfusion injury. Type 2 diabetes mellitus patients have reduced glycolysis in the heart. Objective: We hypothesized that cardioprotection by GLP-1 is achieved through increased glucose availability and utilization and aimed to assess the effect of exenatide, a synthetic GLP-1 receptor agonist, on myocardial glucose uptake (MGU), myocardial glucose transport, and myocardial blood flow (MBF). Design and Methods: We conducted a randomized, double-blinded, placebo-controlled crossover study in eight male, insulin-naive, type 2 diabetes mellitus patients without coronary artery disease. Positron emission tomography was used to determine the effect of exenatide on MGU and MBF during a pituitary-pancreatic hyperglycemic clamp with 18F-fluorodeoxyglucose and 13N-ammonia as tracers. Results: Overall, exenatide did not alter MGU. However, regression analysis revealed that exenatide altered initial clearance of glucose over the membrane of cardiomyocytes and MGU, depending on the level of insulin resistance (P±0.017 and 0.010, respectively). Exenatide increased MBF from 0.73 ± 0.094 to 0.85 ± 0.091 ml/g ± min (P ± 0.0056). Except for an increase in C-peptide levels, no differences in circulating hormones or metabolites were found. Conclusions: The action of exenatide as an activator or inhibitor of the glucose transport and glucose uptake in cardiomyocytes is dependentonbaseline activity of glucose transport and insulin resistance. Exenatide increases MBF without changing MGU.",

keywords = "Biological Transport, Coronary Circulation, Cross-Over Studies, Diabetes Mellitus, Type 2, Double-Blind Method, Glucose, Heart, Humans, Hypoglycemic Agents, Insulin Resistance, Male, Middle Aged, Myocardium, Peptides, Placebos, Positron-Emission Tomography, Regional Blood Flow, Up-Regulation, Venoms",

author = "M Gejl and S{\o}ndergaard, {H M} and Stecher, {Chalotte Willemann} and Bibby, {Bo Martin} and N M{\o}ller and B{\o}tker, {H E} and Hansen, {S B} and Albert Gjedde and J{\o}rgen Rungby and B Brock",

year = "2012",

month = jul,

doi = "10.1210/jc.2011-3456",

language = "English",

volume = "97",

pages = "E1165--9",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "7",

}

TY - JOUR

T1 - Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes

AU - Gejl, M

AU - Søndergaard, H M

AU - Stecher, Chalotte Willemann

AU - Bibby, Bo Martin

AU - Møller, N

AU - Bøtker, H E

AU - Hansen, S B

AU - Gjedde, Albert

AU - Rungby, Jørgen

AU - Brock, B

PY - 2012/7

Y1 - 2012/7

N2 - Context: Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists provide beneficial cardiovascular effects by protecting against ischemia and reperfusion injury. Type 2 diabetes mellitus patients have reduced glycolysis in the heart. Objective: We hypothesized that cardioprotection by GLP-1 is achieved through increased glucose availability and utilization and aimed to assess the effect of exenatide, a synthetic GLP-1 receptor agonist, on myocardial glucose uptake (MGU), myocardial glucose transport, and myocardial blood flow (MBF). Design and Methods: We conducted a randomized, double-blinded, placebo-controlled crossover study in eight male, insulin-naive, type 2 diabetes mellitus patients without coronary artery disease. Positron emission tomography was used to determine the effect of exenatide on MGU and MBF during a pituitary-pancreatic hyperglycemic clamp with 18F-fluorodeoxyglucose and 13N-ammonia as tracers. Results: Overall, exenatide did not alter MGU. However, regression analysis revealed that exenatide altered initial clearance of glucose over the membrane of cardiomyocytes and MGU, depending on the level of insulin resistance (P±0.017 and 0.010, respectively). Exenatide increased MBF from 0.73 ± 0.094 to 0.85 ± 0.091 ml/g ± min (P ± 0.0056). Except for an increase in C-peptide levels, no differences in circulating hormones or metabolites were found. Conclusions: The action of exenatide as an activator or inhibitor of the glucose transport and glucose uptake in cardiomyocytes is dependentonbaseline activity of glucose transport and insulin resistance. Exenatide increases MBF without changing MGU.

AB - Context: Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists provide beneficial cardiovascular effects by protecting against ischemia and reperfusion injury. Type 2 diabetes mellitus patients have reduced glycolysis in the heart. Objective: We hypothesized that cardioprotection by GLP-1 is achieved through increased glucose availability and utilization and aimed to assess the effect of exenatide, a synthetic GLP-1 receptor agonist, on myocardial glucose uptake (MGU), myocardial glucose transport, and myocardial blood flow (MBF). Design and Methods: We conducted a randomized, double-blinded, placebo-controlled crossover study in eight male, insulin-naive, type 2 diabetes mellitus patients without coronary artery disease. Positron emission tomography was used to determine the effect of exenatide on MGU and MBF during a pituitary-pancreatic hyperglycemic clamp with 18F-fluorodeoxyglucose and 13N-ammonia as tracers. Results: Overall, exenatide did not alter MGU. However, regression analysis revealed that exenatide altered initial clearance of glucose over the membrane of cardiomyocytes and MGU, depending on the level of insulin resistance (P±0.017 and 0.010, respectively). Exenatide increased MBF from 0.73 ± 0.094 to 0.85 ± 0.091 ml/g ± min (P ± 0.0056). Except for an increase in C-peptide levels, no differences in circulating hormones or metabolites were found. Conclusions: The action of exenatide as an activator or inhibitor of the glucose transport and glucose uptake in cardiomyocytes is dependentonbaseline activity of glucose transport and insulin resistance. Exenatide increases MBF without changing MGU.

KW - Biological Transport

KW - Coronary Circulation

KW - Cross-Over Studies

KW - Diabetes Mellitus, Type 2

KW - Double-Blind Method

KW - Glucose

KW - Heart

KW - Humans

KW - Hypoglycemic Agents

KW - Insulin Resistance

KW - Male

KW - Middle Aged

KW - Myocardium

KW - Peptides

KW - Placebos

KW - Positron-Emission Tomography

KW - Regional Blood Flow

KW - Up-Regulation

KW - Venoms

U2 - 10.1210/jc.2011-3456

DO - 10.1210/jc.2011-3456

M3 - Journal article

C2 - 22544917

SN - 0021-972X

VL - 97

SP - E1165-9

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 7

ER -

Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes

Abstract

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