GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1 alpha Mutation Carriers

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GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1 alpha Mutation Carriers. / Christensen, Alexander S.; Haedersdal, Sofie; Storgaard, Heidi; Rose, Kathrine; Hansen, Nina L.; Holst, Jens J.; Hansen, Torben; Knop, Filip K.; Vilsboll, Tina.

In: Diabetes, Vol. 69, No. 9, 2020, p. 1989-2002.

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

Harvard

Christensen, AS, Haedersdal, S, Storgaard, H, Rose, K, Hansen, NL, Holst, JJ, Hansen, T, Knop, FK & Vilsboll, T 2020, 'GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1 alpha Mutation Carriers', Diabetes, vol. 69, no. 9, pp. 1989-2002. https://doi.org/10.2337/db20-0074

APA

Christensen, A. S., Haedersdal, S., Storgaard, H., Rose, K., Hansen, N. L., Holst, J. J., Hansen, T., Knop, F. K., & Vilsboll, T. (2020). GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1 alpha Mutation Carriers. Diabetes, 69(9), 1989-2002. https://doi.org/10.2337/db20-0074

Vancouver

Christensen AS, Haedersdal S, Storgaard H, Rose K, Hansen NL, Holst JJ et al. GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1 alpha Mutation Carriers. Diabetes. 2020;69(9):1989-2002. https://doi.org/10.2337/db20-0074

Author

Christensen, Alexander S. ; Haedersdal, Sofie ; Storgaard, Heidi ; Rose, Kathrine ; Hansen, Nina L. ; Holst, Jens J. ; Hansen, Torben ; Knop, Filip K. ; Vilsboll, Tina. / GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1 alpha Mutation Carriers. In: Diabetes. 2020 ; Vol. 69, No. 9. pp. 1989-2002.

Bibtex

@article{6bf1f01fdf6b4ff68e447143653ef397,
title = "GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1 alpha Mutation Carriers",
abstract = "Sulfonylureas (SUs) provide an efficacious first-line treatment in patients with hepatocyte nuclear factor 1 alpha (HNF1A) diabetes, but SUs have limitations due to risk of hypoglycemia. Treatment based on the incretin hormones glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1) is characterized by their glucose-dependent insulinotropic actions without risk of hypoglycemia. The effect of SUs together with GIP or GLP-1, respectively, on insulin and glucagon secretion in patients with HNF1A diabetes is currently unknown. To investigate this, 10HNF1Amutation carriers and 10 control subjects without diabetes were recruited for a double-blinded, placebo-controlled, crossover study including 6 experimental days in a randomized order involving 2-h euglycemic-hyperglycemic clamps with coadministration of:1) SU (glimepiride 1 mg) or placebo, combined with2) infusions of GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min), or saline (NaCl). InHNF1Amutation carriers, we observed:1) hypoinsulinemia,2) insulinotropic effects of both GIP and GLP-1,3) additive to supra-additive effects on insulin secretion when combining SU+GIP and SU+GLP-1, respectively, and4) increased fasting and arginine-induced glucagon levels compared with control subjects without diabetes. Our study suggests that a combination of SU and incretin-based treatment may be efficacious in patients with HNF1A diabetes via potentiation of glucose-stimulated insulin secretion.",
keywords = "PANCREATIC BETA-CELLS, GLUCOSE CONTROL, YOUNG, RISK, PATHOPHYSIOLOGY, COMPLICATIONS, HYPOGLYCEMIA, RESPONSES, PLASMA, GENE",
author = "Christensen, {Alexander S.} and Sofie Haedersdal and Heidi Storgaard and Kathrine Rose and Hansen, {Nina L.} and Holst, {Jens J.} and Torben Hansen and Knop, {Filip K.} and Tina Vilsboll",
year = "2020",
doi = "10.2337/db20-0074",
language = "English",
volume = "69",
pages = "1989--2002",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "9",

}

RIS

TY - JOUR

T1 - GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1 alpha Mutation Carriers

AU - Christensen, Alexander S.

AU - Haedersdal, Sofie

AU - Storgaard, Heidi

AU - Rose, Kathrine

AU - Hansen, Nina L.

AU - Holst, Jens J.

AU - Hansen, Torben

AU - Knop, Filip K.

AU - Vilsboll, Tina

PY - 2020

Y1 - 2020

N2 - Sulfonylureas (SUs) provide an efficacious first-line treatment in patients with hepatocyte nuclear factor 1 alpha (HNF1A) diabetes, but SUs have limitations due to risk of hypoglycemia. Treatment based on the incretin hormones glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1) is characterized by their glucose-dependent insulinotropic actions without risk of hypoglycemia. The effect of SUs together with GIP or GLP-1, respectively, on insulin and glucagon secretion in patients with HNF1A diabetes is currently unknown. To investigate this, 10HNF1Amutation carriers and 10 control subjects without diabetes were recruited for a double-blinded, placebo-controlled, crossover study including 6 experimental days in a randomized order involving 2-h euglycemic-hyperglycemic clamps with coadministration of:1) SU (glimepiride 1 mg) or placebo, combined with2) infusions of GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min), or saline (NaCl). InHNF1Amutation carriers, we observed:1) hypoinsulinemia,2) insulinotropic effects of both GIP and GLP-1,3) additive to supra-additive effects on insulin secretion when combining SU+GIP and SU+GLP-1, respectively, and4) increased fasting and arginine-induced glucagon levels compared with control subjects without diabetes. Our study suggests that a combination of SU and incretin-based treatment may be efficacious in patients with HNF1A diabetes via potentiation of glucose-stimulated insulin secretion.

AB - Sulfonylureas (SUs) provide an efficacious first-line treatment in patients with hepatocyte nuclear factor 1 alpha (HNF1A) diabetes, but SUs have limitations due to risk of hypoglycemia. Treatment based on the incretin hormones glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1) is characterized by their glucose-dependent insulinotropic actions without risk of hypoglycemia. The effect of SUs together with GIP or GLP-1, respectively, on insulin and glucagon secretion in patients with HNF1A diabetes is currently unknown. To investigate this, 10HNF1Amutation carriers and 10 control subjects without diabetes were recruited for a double-blinded, placebo-controlled, crossover study including 6 experimental days in a randomized order involving 2-h euglycemic-hyperglycemic clamps with coadministration of:1) SU (glimepiride 1 mg) or placebo, combined with2) infusions of GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min), or saline (NaCl). InHNF1Amutation carriers, we observed:1) hypoinsulinemia,2) insulinotropic effects of both GIP and GLP-1,3) additive to supra-additive effects on insulin secretion when combining SU+GIP and SU+GLP-1, respectively, and4) increased fasting and arginine-induced glucagon levels compared with control subjects without diabetes. Our study suggests that a combination of SU and incretin-based treatment may be efficacious in patients with HNF1A diabetes via potentiation of glucose-stimulated insulin secretion.

KW - PANCREATIC BETA-CELLS

KW - GLUCOSE CONTROL

KW - YOUNG

KW - RISK

KW - PATHOPHYSIOLOGY

KW - COMPLICATIONS

KW - HYPOGLYCEMIA

KW - RESPONSES

KW - PLASMA

KW - GENE

U2 - 10.2337/db20-0074

DO - 10.2337/db20-0074

M3 - Journal article

C2 - 32518064

VL - 69

SP - 1989

EP - 2002

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 9

ER -

ID: 247540733