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

Autor: M. Sands, W. Zhang, Christian Meyer, S. Sinha, T. Osredkar, J. Koska, P. D. Reaven, K. D'Souza
Rok vydání: 2019
Předmět:
Adult
Blood Glucose
Male
medicine.medical_specialty
Endothelium
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Adipose tissue
Adamantane
030209 endocrinology & metabolism
Inflammation
Saxagliptin
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Double-Blind Method
Internal medicine
Internal Medicine
medicine
Humans
Obesity
030212 general & internal medicine
Cells
Cultured
Aged
Glycated Hemoglobin
Dipeptidyl-Peptidase IV Inhibitors
Dose-Response Relationship
Drug
Triglyceride
business.industry
Insulin
Endothelial Cells
Dipeptides
Middle Aged
Overweight
Postprandial Period
Immunohistochemistry
Treatment Outcome
medicine.anatomical_structure
Postprandial
Adipose Tissue
chemistry
Female
Endothelium
Vascular
medicine.symptom
business
TXNIP
Zdroj: Diabetic Medicine. 36:1399-1407
ISSN: 1464-5491
0742-3071
DOI: 10.1111/dme.13889
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: