Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes

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Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes. / Steenberg, Vivi R.; Jensen, Signe Marie; Pedersen, Jens; Madsen, Andreas N.; Windeloev, Johanne A.; Holst, Birgitte; Quistorff, Bjoern; Poulsen, Steen S.; Holst, Jens J.

In: Diabetologia, Vol. 59, No. 2, 2016, p. 363-370.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Steenberg, VR, Jensen, SM, Pedersen, J, Madsen, AN, Windeloev, JA, Holst, B, Quistorff, B, Poulsen, SS & Holst, JJ 2016, 'Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes', Diabetologia, vol. 59, no. 2, pp. 363-370. https://doi.org/10.1007/s00125-015-3794-2

APA

Steenberg, V. R., Jensen, S. M., Pedersen, J., Madsen, A. N., Windeloev, J. A., Holst, B., ... Holst, J. J. (2016). Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes. Diabetologia, 59(2), 363-370. https://doi.org/10.1007/s00125-015-3794-2

Vancouver

Steenberg VR, Jensen SM, Pedersen J, Madsen AN, Windeloev JA, Holst B et al. Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes. Diabetologia. 2016;59(2):363-370. https://doi.org/10.1007/s00125-015-3794-2

Author

Steenberg, Vivi R. ; Jensen, Signe Marie ; Pedersen, Jens ; Madsen, Andreas N. ; Windeloev, Johanne A. ; Holst, Birgitte ; Quistorff, Bjoern ; Poulsen, Steen S. ; Holst, Jens J. / Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes. In: Diabetologia. 2016 ; Vol. 59, No. 2. pp. 363-370.

Bibtex

@article{c9870b442d5a4cb5a5f7fd369bf33800,
title = "Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes",
abstract = "Aims/hypothesis: Normal glucose metab. depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilization, glucagon excess is the principal factor in diabetic glucose overprodn. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance. Methods: Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metab. was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist. Results: Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass. Conclusions/interpretation: Disruption of glucagon action/secretion did not improve glucose tolerance in diabetic mice. Near-total alpha cell elimination may have prevented further deterioration. Our findings support insulin lack as the major factor underlying hyperglycemia in beta cell-deficient diabetes. [on SciFinder(R)]",
author = "Steenberg, {Vivi R.} and Jensen, {Signe Marie} and Jens Pedersen and Madsen, {Andreas N.} and Windeloev, {Johanne A.} and Birgitte Holst and Bjoern Quistorff and Poulsen, {Steen S.} and Holst, {Jens J.}",
note = "M1 - Copyright (C) 2015 American Chemical Society (ACS). All Rights Reserved. CAPLUS AN 2015:1829020(Journal)",
year = "2016",
doi = "10.1007/s00125-015-3794-2",
language = "English",
volume = "59",
pages = "363--370",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "2",

}

RIS

TY - JOUR

T1 - Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes

AU - Steenberg, Vivi R.

AU - Jensen, Signe Marie

AU - Pedersen, Jens

AU - Madsen, Andreas N.

AU - Windeloev, Johanne A.

AU - Holst, Birgitte

AU - Quistorff, Bjoern

AU - Poulsen, Steen S.

AU - Holst, Jens J.

N1 - M1 - Copyright (C) 2015 American Chemical Society (ACS). All Rights Reserved. CAPLUS AN 2015:1829020(Journal)

PY - 2016

Y1 - 2016

N2 - Aims/hypothesis: Normal glucose metab. depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilization, glucagon excess is the principal factor in diabetic glucose overprodn. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance. Methods: Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metab. was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist. Results: Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass. Conclusions/interpretation: Disruption of glucagon action/secretion did not improve glucose tolerance in diabetic mice. Near-total alpha cell elimination may have prevented further deterioration. Our findings support insulin lack as the major factor underlying hyperglycemia in beta cell-deficient diabetes. [on SciFinder(R)]

AB - Aims/hypothesis: Normal glucose metab. depends on pancreatic secretion of insulin and glucagon. The bihormonal hypothesis states that while lack of insulin leads to glucose underutilization, glucagon excess is the principal factor in diabetic glucose overprodn. A recent study reported that streptozotocin-treated glucagon receptor knockout mice have normal glucose tolerance. We investigated the impact of acute disruption of glucagon secretin or action in a mouse model of severe diabetes by three different approaches: (1) alpha cell elimination; (2) glucagon immunoneutralisation; and (3) glucagon receptor antagonism, in order to evaluate the effect of these on glucose tolerance. Methods: Severe diabetes was induced in transgenic and wild-type mice by streptozotocin. Glucose metab. was investigated using OGTT in transgenic mice with the human diphtheria toxin receptor expressed in proglucagon producing cells allowing for diphtheria toxin (DT)-induced alpha cell ablation and in mice treated with either a specific high affinity glucagon antibody or a specific glucagon receptor antagonist. Results: Near-total alpha cell elimination was induced in transgenic mice upon DT administration and resulted in a massive decrease in pancreatic glucagon content. Oral glucose tolerance in diabetic mice was neither affected by glucagon immunoneutralisation, glucagon receptor antagonism, nor alpha cell removal, but did not deteriorate further compared with mice with intact alpha cell mass. Conclusions/interpretation: Disruption of glucagon action/secretion did not improve glucose tolerance in diabetic mice. Near-total alpha cell elimination may have prevented further deterioration. Our findings support insulin lack as the major factor underlying hyperglycemia in beta cell-deficient diabetes. [on SciFinder(R)]

U2 - 10.1007/s00125-015-3794-2

DO - 10.1007/s00125-015-3794-2

M3 - Journal article

VL - 59

SP - 363

EP - 370

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 2

ER -

ID: 150700584