Combined insulin deficiency and endotoxin exposure stimulate lipid mobilization and alter adipose tissue signaling in an experimental model of ketoacidosis in subjects with type 1 diabetes: A randomized, controlled, cross over trial

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

Standard

Combined insulin deficiency and endotoxin exposure stimulate lipid mobilization and alter adipose tissue signaling in an experimental model of ketoacidosis in subjects with type 1 diabetes : A randomized, controlled, cross over trial. / Svart, Mads; Kampmann, Ulla; Voss, Thomas; Pedersen, Steen B; Johannsen, Mogens; Rittig, Nikolaj; Poulsen, Per L; Nielsen, Thomas S; Jessen, Niels; Møller, Niels.

In: Diabetes, Vol. 65, No. 5, 05.2016, p. 1380-6.

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

Harvard

Svart, M, Kampmann, U, Voss, T, Pedersen, SB, Johannsen, M, Rittig, N, Poulsen, PL, Nielsen, TS, Jessen, N & Møller, N 2016, 'Combined insulin deficiency and endotoxin exposure stimulate lipid mobilization and alter adipose tissue signaling in an experimental model of ketoacidosis in subjects with type 1 diabetes: A randomized, controlled, cross over trial', Diabetes, vol. 65, no. 5, pp. 1380-6. https://doi.org/10.2337/db15-1645

APA

Svart, M., Kampmann, U., Voss, T., Pedersen, S. B., Johannsen, M., Rittig, N., Poulsen, P. L., Nielsen, T. S., Jessen, N., & Møller, N. (2016). Combined insulin deficiency and endotoxin exposure stimulate lipid mobilization and alter adipose tissue signaling in an experimental model of ketoacidosis in subjects with type 1 diabetes: A randomized, controlled, cross over trial. Diabetes, 65(5), 1380-6. https://doi.org/10.2337/db15-1645

Vancouver

Svart M, Kampmann U, Voss T, Pedersen SB, Johannsen M, Rittig N et al. Combined insulin deficiency and endotoxin exposure stimulate lipid mobilization and alter adipose tissue signaling in an experimental model of ketoacidosis in subjects with type 1 diabetes: A randomized, controlled, cross over trial. Diabetes. 2016 May;65(5):1380-6. https://doi.org/10.2337/db15-1645

Author

Svart, Mads ; Kampmann, Ulla ; Voss, Thomas ; Pedersen, Steen B ; Johannsen, Mogens ; Rittig, Nikolaj ; Poulsen, Per L ; Nielsen, Thomas S ; Jessen, Niels ; Møller, Niels. / Combined insulin deficiency and endotoxin exposure stimulate lipid mobilization and alter adipose tissue signaling in an experimental model of ketoacidosis in subjects with type 1 diabetes : A randomized, controlled, cross over trial. In: Diabetes. 2016 ; Vol. 65, No. 5. pp. 1380-6.

Bibtex

@article{40761483a2f244f48c35751a64390669,
title = "Combined insulin deficiency and endotoxin exposure stimulate lipid mobilization and alter adipose tissue signaling in an experimental model of ketoacidosis in subjects with type 1 diabetes: A randomized, controlled, cross over trial",
abstract = "Most often diabetic ketoacidosis (DKA) in adults results from insufficient insulin administration and acute infection. It is assumed that this releases proinflammatory cytokines and stress hormones, which stimulate lipolysis and ketogenesis.We aimed to test whether this perception of DKA can be reproduced in an experimental human model utilizing combined insulin deficiency and acute inflammation and which intracellular mediators of lipolysis are affected in adipose tissue.Nine type 1 diabetic subjects were studied twice: (i) insulin controlled euglycemia(CTR) and (ii) insulin deprivation and endotoxin administration(KET).During KET, serum TNF-α, cortisol, glucagon, and growth hormone levels increased; free fatty acids and 3-hydroxybutyrate concentrations and the rate of lipolysis rose markedly. Serum bicarbonate and pH decreased. Adipose tissue mRNA contents of comparative gene identification-58 (CGI-58) increased and G0/G1 switch 2 gene (G0S2) mRNA decreased robustly. Neither protein levels of adipose triglyceride lipase (ATGL) nor phosphorylations of hormone sensitive lipase were altered.The clinical picture of incipient DKA in adults can be reproduced by combined insulin deficiency and endotoxin induced acute inflammation. The precipitating steps involve release of proinflammatory cytokines and stress hormones, increased lipolysis and decreased G0S2 and increased CGI-58 mRNA contents in adipose tissue, compatible with latent ATGL stimulation.",
author = "Mads Svart and Ulla Kampmann and Thomas Voss and Pedersen, {Steen B} and Mogens Johannsen and Nikolaj Rittig and Poulsen, {Per L} and Nielsen, {Thomas S} and Niels Jessen and Niels M{\o}ller",
note = "{\textcopyright} 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.",
year = "2016",
month = may,
doi = "10.2337/db15-1645",
language = "English",
volume = "65",
pages = "1380--6",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "5",

}

RIS

TY - JOUR

T1 - Combined insulin deficiency and endotoxin exposure stimulate lipid mobilization and alter adipose tissue signaling in an experimental model of ketoacidosis in subjects with type 1 diabetes

T2 - A randomized, controlled, cross over trial

AU - Svart, Mads

AU - Kampmann, Ulla

AU - Voss, Thomas

AU - Pedersen, Steen B

AU - Johannsen, Mogens

AU - Rittig, Nikolaj

AU - Poulsen, Per L

AU - Nielsen, Thomas S

AU - Jessen, Niels

AU - Møller, Niels

N1 - © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PY - 2016/5

Y1 - 2016/5

N2 - Most often diabetic ketoacidosis (DKA) in adults results from insufficient insulin administration and acute infection. It is assumed that this releases proinflammatory cytokines and stress hormones, which stimulate lipolysis and ketogenesis.We aimed to test whether this perception of DKA can be reproduced in an experimental human model utilizing combined insulin deficiency and acute inflammation and which intracellular mediators of lipolysis are affected in adipose tissue.Nine type 1 diabetic subjects were studied twice: (i) insulin controlled euglycemia(CTR) and (ii) insulin deprivation and endotoxin administration(KET).During KET, serum TNF-α, cortisol, glucagon, and growth hormone levels increased; free fatty acids and 3-hydroxybutyrate concentrations and the rate of lipolysis rose markedly. Serum bicarbonate and pH decreased. Adipose tissue mRNA contents of comparative gene identification-58 (CGI-58) increased and G0/G1 switch 2 gene (G0S2) mRNA decreased robustly. Neither protein levels of adipose triglyceride lipase (ATGL) nor phosphorylations of hormone sensitive lipase were altered.The clinical picture of incipient DKA in adults can be reproduced by combined insulin deficiency and endotoxin induced acute inflammation. The precipitating steps involve release of proinflammatory cytokines and stress hormones, increased lipolysis and decreased G0S2 and increased CGI-58 mRNA contents in adipose tissue, compatible with latent ATGL stimulation.

AB - Most often diabetic ketoacidosis (DKA) in adults results from insufficient insulin administration and acute infection. It is assumed that this releases proinflammatory cytokines and stress hormones, which stimulate lipolysis and ketogenesis.We aimed to test whether this perception of DKA can be reproduced in an experimental human model utilizing combined insulin deficiency and acute inflammation and which intracellular mediators of lipolysis are affected in adipose tissue.Nine type 1 diabetic subjects were studied twice: (i) insulin controlled euglycemia(CTR) and (ii) insulin deprivation and endotoxin administration(KET).During KET, serum TNF-α, cortisol, glucagon, and growth hormone levels increased; free fatty acids and 3-hydroxybutyrate concentrations and the rate of lipolysis rose markedly. Serum bicarbonate and pH decreased. Adipose tissue mRNA contents of comparative gene identification-58 (CGI-58) increased and G0/G1 switch 2 gene (G0S2) mRNA decreased robustly. Neither protein levels of adipose triglyceride lipase (ATGL) nor phosphorylations of hormone sensitive lipase were altered.The clinical picture of incipient DKA in adults can be reproduced by combined insulin deficiency and endotoxin induced acute inflammation. The precipitating steps involve release of proinflammatory cytokines and stress hormones, increased lipolysis and decreased G0S2 and increased CGI-58 mRNA contents in adipose tissue, compatible with latent ATGL stimulation.

U2 - 10.2337/db15-1645

DO - 10.2337/db15-1645

M3 - Journal article

C2 - 26884439

VL - 65

SP - 1380

EP - 1386

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 5

ER -

ID: 156083914