Effects of saxagliptin on adipose tissue inflammation and vascular function in overweight and obese people: a placebo-controlled study

J. Koska, T. Osredkar, K. D'Souza, M. Sands, S. Sinha, W. Zhang, C. Meyer, P. D. Reaven

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aims: To test the effect of the dipeptidyl peptidase-4 inhibitor saxagliptin on adipose tissue inflammation and microvascular function, and whole-body postprandial endothelial function. Methods: A randomized, double-blind, placebo-controlled, parallel study was conducted between June 2013 and November 2016 in 44 overweight or obese people without diabetes (saxagliptin, n=28; placebo, n=16). Subcutaneous abdominal adipose tissue biopsies, a 4-h fat-enriched meal test and peripheral arterial tonometry for measurement of endothelial function were performed at baseline and after 6 weeks of treatment with saxagliptin (5 mg/day) or matching placebo. Results: Forty participants were analysed (saxagliptin, n=26; placebo, n=14). Secretion of interleukin-8 from adipose tissue explants was reduced after saxagliptin (median fold-change from baseline: 0.8 saxagliptin vs 3.3 placebo; P=0.02). Adipose tissue expression of thioredoxin-inhibitory protein (TxNIP) was lower after saxagliptin (0.75 vs 1.0; P=0.02), while there were no significant differences in adipose tissue secretion of interleukin-1b, interleukin-6 or macrophage chemoattractant protein 1 (MCP-1), adipose tissue macrophage content, adipose tissue mRNA levels of mcp1, cd36, cd68, il6, il8, txnip and adpq, and activation of adipose tissue inflammatory pathways [extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF- κB)] or insulin-induced vasodilation of adipose tissue arterioles. Postprandial plasma glucose was slightly lower (by an estimated 0.3 mmol/l; P=0.01), while postprandial insulin, triglyceride levels and endothelial function were unchanged after saxagliptin. Conclusions: The effect of saxagliptin on adipose tissue inflammation was relatively modest, with many inflammatory markers unchanged. We also found no evidence that saxagliptin therapy improved adipose tissue arteriole vasodilation or postprandial endothelial function.

Original languageEnglish (US)
Pages (from-to)1399-1407
Number of pages9
JournalDiabetic Medicine
Volume36
Issue number11
DOIs
StatePublished - Nov 1 2019
Externally publishedYes

Fingerprint

Blood Vessels
Adipose Tissue
Placebos
Inflammation
Arterioles
Vasodilation
Macrophages
saxagliptin
Abdominal Subcutaneous Fat
Dipeptidyl-Peptidase IV Inhibitors
Thioredoxins
JNK Mitogen-Activated Protein Kinases
Interleukins
Chemotactic Factors
Extracellular Signal-Regulated MAP Kinases
Manometry
Interleukin-8
Meals
Interleukin-6
Triglycerides

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Effects of saxagliptin on adipose tissue inflammation and vascular function in overweight and obese people : a placebo-controlled study. / Koska, J.; Osredkar, T.; D'Souza, K.; Sands, M.; Sinha, S.; Zhang, W.; Meyer, C.; Reaven, P. D.

In: Diabetic Medicine, Vol. 36, No. 11, 01.11.2019, p. 1399-1407.

Research output: Contribution to journalArticle

Koska, J. ; Osredkar, T. ; D'Souza, K. ; Sands, M. ; Sinha, S. ; Zhang, W. ; Meyer, C. ; Reaven, P. D. / Effects of saxagliptin on adipose tissue inflammation and vascular function in overweight and obese people : a placebo-controlled study. In: Diabetic Medicine. 2019 ; Vol. 36, No. 11. pp. 1399-1407.
@article{341cffcbcce54e25aae3d7f5f6e9ac88,
title = "Effects of saxagliptin on adipose tissue inflammation and vascular function in overweight and obese people: a placebo-controlled study",
abstract = "Aims: To test the effect of the dipeptidyl peptidase-4 inhibitor saxagliptin on adipose tissue inflammation and microvascular function, and whole-body postprandial endothelial function. Methods: A randomized, double-blind, placebo-controlled, parallel study was conducted between June 2013 and November 2016 in 44 overweight or obese people without diabetes (saxagliptin, n=28; placebo, n=16). Subcutaneous abdominal adipose tissue biopsies, a 4-h fat-enriched meal test and peripheral arterial tonometry for measurement of endothelial function were performed at baseline and after 6 weeks of treatment with saxagliptin (5 mg/day) or matching placebo. Results: Forty participants were analysed (saxagliptin, n=26; placebo, n=14). Secretion of interleukin-8 from adipose tissue explants was reduced after saxagliptin (median fold-change from baseline: 0.8 saxagliptin vs 3.3 placebo; P=0.02). Adipose tissue expression of thioredoxin-inhibitory protein (TxNIP) was lower after saxagliptin (0.75 vs 1.0; P=0.02), while there were no significant differences in adipose tissue secretion of interleukin-1b, interleukin-6 or macrophage chemoattractant protein 1 (MCP-1), adipose tissue macrophage content, adipose tissue mRNA levels of mcp1, cd36, cd68, il6, il8, txnip and adpq, and activation of adipose tissue inflammatory pathways [extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF- κB)] or insulin-induced vasodilation of adipose tissue arterioles. Postprandial plasma glucose was slightly lower (by an estimated 0.3 mmol/l; P=0.01), while postprandial insulin, triglyceride levels and endothelial function were unchanged after saxagliptin. Conclusions: The effect of saxagliptin on adipose tissue inflammation was relatively modest, with many inflammatory markers unchanged. We also found no evidence that saxagliptin therapy improved adipose tissue arteriole vasodilation or postprandial endothelial function.",
author = "J. Koska and T. Osredkar and K. D'Souza and M. Sands and S. Sinha and W. Zhang and C. Meyer and Reaven, {P. D.}",
year = "2019",
month = "11",
day = "1",
doi = "10.1111/dme.13889",
language = "English (US)",
volume = "36",
pages = "1399--1407",
journal = "Diabetic Medicine",
issn = "0742-3071",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - Effects of saxagliptin on adipose tissue inflammation and vascular function in overweight and obese people

T2 - a placebo-controlled study

AU - Koska, J.

AU - Osredkar, T.

AU - D'Souza, K.

AU - Sands, M.

AU - Sinha, S.

AU - Zhang, W.

AU - Meyer, C.

AU - Reaven, P. D.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Aims: To test the effect of the dipeptidyl peptidase-4 inhibitor saxagliptin on adipose tissue inflammation and microvascular function, and whole-body postprandial endothelial function. Methods: A randomized, double-blind, placebo-controlled, parallel study was conducted between June 2013 and November 2016 in 44 overweight or obese people without diabetes (saxagliptin, n=28; placebo, n=16). Subcutaneous abdominal adipose tissue biopsies, a 4-h fat-enriched meal test and peripheral arterial tonometry for measurement of endothelial function were performed at baseline and after 6 weeks of treatment with saxagliptin (5 mg/day) or matching placebo. Results: Forty participants were analysed (saxagliptin, n=26; placebo, n=14). Secretion of interleukin-8 from adipose tissue explants was reduced after saxagliptin (median fold-change from baseline: 0.8 saxagliptin vs 3.3 placebo; P=0.02). Adipose tissue expression of thioredoxin-inhibitory protein (TxNIP) was lower after saxagliptin (0.75 vs 1.0; P=0.02), while there were no significant differences in adipose tissue secretion of interleukin-1b, interleukin-6 or macrophage chemoattractant protein 1 (MCP-1), adipose tissue macrophage content, adipose tissue mRNA levels of mcp1, cd36, cd68, il6, il8, txnip and adpq, and activation of adipose tissue inflammatory pathways [extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF- κB)] or insulin-induced vasodilation of adipose tissue arterioles. Postprandial plasma glucose was slightly lower (by an estimated 0.3 mmol/l; P=0.01), while postprandial insulin, triglyceride levels and endothelial function were unchanged after saxagliptin. Conclusions: The effect of saxagliptin on adipose tissue inflammation was relatively modest, with many inflammatory markers unchanged. We also found no evidence that saxagliptin therapy improved adipose tissue arteriole vasodilation or postprandial endothelial function.

AB - Aims: To test the effect of the dipeptidyl peptidase-4 inhibitor saxagliptin on adipose tissue inflammation and microvascular function, and whole-body postprandial endothelial function. Methods: A randomized, double-blind, placebo-controlled, parallel study was conducted between June 2013 and November 2016 in 44 overweight or obese people without diabetes (saxagliptin, n=28; placebo, n=16). Subcutaneous abdominal adipose tissue biopsies, a 4-h fat-enriched meal test and peripheral arterial tonometry for measurement of endothelial function were performed at baseline and after 6 weeks of treatment with saxagliptin (5 mg/day) or matching placebo. Results: Forty participants were analysed (saxagliptin, n=26; placebo, n=14). Secretion of interleukin-8 from adipose tissue explants was reduced after saxagliptin (median fold-change from baseline: 0.8 saxagliptin vs 3.3 placebo; P=0.02). Adipose tissue expression of thioredoxin-inhibitory protein (TxNIP) was lower after saxagliptin (0.75 vs 1.0; P=0.02), while there were no significant differences in adipose tissue secretion of interleukin-1b, interleukin-6 or macrophage chemoattractant protein 1 (MCP-1), adipose tissue macrophage content, adipose tissue mRNA levels of mcp1, cd36, cd68, il6, il8, txnip and adpq, and activation of adipose tissue inflammatory pathways [extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF- κB)] or insulin-induced vasodilation of adipose tissue arterioles. Postprandial plasma glucose was slightly lower (by an estimated 0.3 mmol/l; P=0.01), while postprandial insulin, triglyceride levels and endothelial function were unchanged after saxagliptin. Conclusions: The effect of saxagliptin on adipose tissue inflammation was relatively modest, with many inflammatory markers unchanged. We also found no evidence that saxagliptin therapy improved adipose tissue arteriole vasodilation or postprandial endothelial function.

UR - http://www.scopus.com/inward/record.url?scp=85060348053&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060348053&partnerID=8YFLogxK

U2 - 10.1111/dme.13889

DO - 10.1111/dme.13889

M3 - Article

C2 - 30580454

AN - SCOPUS:85060348053

VL - 36

SP - 1399

EP - 1407

JO - Diabetic Medicine

JF - Diabetic Medicine

SN - 0742-3071

IS - 11

ER -