Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte’s secretome

Abstract Background Adipose tissue secretome plays a crucial role in the mechanisms of metabolic diseases. Weight loss has a favourable effect on the adipose tissue secretome and prevents the development of type 2 diabetes mellitus (T2DM) and its complications. The most effective methods of glycaemi...

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Main Authors: Margarita Agareva, Svetlana Michurina, Alina Tomilova, Ekaterina Shestakova, Anastasia Voznesenskaya, Maria Sineokaya, Ekaterina Zubkova, Elizaveta Ratner, Iurii Stafeev, Yelena Parfyonova, Marina Shestakova
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Endocrine Disorders
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Online Access:https://doi.org/10.1186/s12902-025-01999-w
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author Margarita Agareva
Svetlana Michurina
Alina Tomilova
Ekaterina Shestakova
Anastasia Voznesenskaya
Maria Sineokaya
Ekaterina Zubkova
Elizaveta Ratner
Iurii Stafeev
Yelena Parfyonova
Marina Shestakova
author_facet Margarita Agareva
Svetlana Michurina
Alina Tomilova
Ekaterina Shestakova
Anastasia Voznesenskaya
Maria Sineokaya
Ekaterina Zubkova
Elizaveta Ratner
Iurii Stafeev
Yelena Parfyonova
Marina Shestakova
author_sort Margarita Agareva
collection DOAJ
description Abstract Background Adipose tissue secretome plays a crucial role in the mechanisms of metabolic diseases. Weight loss has a favourable effect on the adipose tissue secretome and prevents the development of type 2 diabetes mellitus (T2DM) and its complications. The most effective methods of glycaemic control are bariatric surgery (BS) and pharmacotherapy. The aim of our study is to evaluate changes in adipose tissue secretome after BS and semaglutide injections. Methods 17 patients with T2DM were examined before and 6 months after BS or semaglutide therapy. The examination protocol included anthropometry, clinical biochemistry, insulin resistance evaluation and collection of subcutaneous adipose tissue biopsies. Adipose derived stem cells (ADSC) were isolated from biopsies according to a standard enzymatic protocol and differentiated into white and beige adipocytes. Adipogenesis and thermogenesis were assessed by confocal microscopy. Secretome of adipocytes and cytokines plasma levels were analyzed using a MILLIPLEX panel. Results Following BS and semaglutide therapy, a decline in BMI, total fat content, HbA1c, and fasting blood glucose was observed. Insulin sensitivity increased only 6 months after BS. Semaglutide therapy resulted in the elevation of angiogenic and proinflammatory cytokines in adipocyte secretory profile. After BS we also detected the increase in proinflammatory cytokines both in adipocyte secretome and in plasma levels. However, the adipocyte secretome subsequent to bariatric surgery (BS) exhibited a reduced proinflammatory response in comparison to that observed following semaglutide therapy. Conclusions The effect of semaglutide injections directly on adipose tissue can change the function of ADSC, making them more angiogenic and adipogenic. A decrease in BMI, HbA1c and insulin resistance is achieved to a significant extent only after BS. BS-induced T2DM remission is related to lower pro-inflammatory secretion from adipocytes as compared to semaglutide. The regulation of inflammation in adipocytes may serve as a potential mechanism underlying BS-induced T2DM remission.
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spelling doaj-art-dc2e3d3ca6474bee833bf85c53a0e1542025-08-20T03:43:15ZengBMCBMC Endocrine Disorders1472-68232025-07-0125111310.1186/s12902-025-01999-wIncretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte’s secretomeMargarita Agareva0Svetlana Michurina1Alina Tomilova2Ekaterina Shestakova3Anastasia Voznesenskaya4Maria Sineokaya5Ekaterina Zubkova6Elizaveta Ratner7Iurii Stafeev8Yelena Parfyonova9Marina Shestakova10National Medical Research Centre of Cardiology named after academician E.I.ChazovNational Medical Research Centre of Cardiology named after academician E.I.ChazovEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreEndocrinology Research CentreNational Medical Research Centre of Cardiology named after academician E.I.ChazovNational Medical Research Centre of Cardiology named after academician E.I.ChazovNational Medical Research Centre of Cardiology named after academician E.I.ChazovNational Medical Research Centre of Cardiology named after academician E.I.ChazovLomonosov Moscow State UniversityAbstract Background Adipose tissue secretome plays a crucial role in the mechanisms of metabolic diseases. Weight loss has a favourable effect on the adipose tissue secretome and prevents the development of type 2 diabetes mellitus (T2DM) and its complications. The most effective methods of glycaemic control are bariatric surgery (BS) and pharmacotherapy. The aim of our study is to evaluate changes in adipose tissue secretome after BS and semaglutide injections. Methods 17 patients with T2DM were examined before and 6 months after BS or semaglutide therapy. The examination protocol included anthropometry, clinical biochemistry, insulin resistance evaluation and collection of subcutaneous adipose tissue biopsies. Adipose derived stem cells (ADSC) were isolated from biopsies according to a standard enzymatic protocol and differentiated into white and beige adipocytes. Adipogenesis and thermogenesis were assessed by confocal microscopy. Secretome of adipocytes and cytokines plasma levels were analyzed using a MILLIPLEX panel. Results Following BS and semaglutide therapy, a decline in BMI, total fat content, HbA1c, and fasting blood glucose was observed. Insulin sensitivity increased only 6 months after BS. Semaglutide therapy resulted in the elevation of angiogenic and proinflammatory cytokines in adipocyte secretory profile. After BS we also detected the increase in proinflammatory cytokines both in adipocyte secretome and in plasma levels. However, the adipocyte secretome subsequent to bariatric surgery (BS) exhibited a reduced proinflammatory response in comparison to that observed following semaglutide therapy. Conclusions The effect of semaglutide injections directly on adipose tissue can change the function of ADSC, making them more angiogenic and adipogenic. A decrease in BMI, HbA1c and insulin resistance is achieved to a significant extent only after BS. BS-induced T2DM remission is related to lower pro-inflammatory secretion from adipocytes as compared to semaglutide. The regulation of inflammation in adipocytes may serve as a potential mechanism underlying BS-induced T2DM remission.https://doi.org/10.1186/s12902-025-01999-wAdipose-derived stem cellsAdipocytesPlasmaSecretomeCytokinesType 2 diabetes
spellingShingle Margarita Agareva
Svetlana Michurina
Alina Tomilova
Ekaterina Shestakova
Anastasia Voznesenskaya
Maria Sineokaya
Ekaterina Zubkova
Elizaveta Ratner
Iurii Stafeev
Yelena Parfyonova
Marina Shestakova
Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte’s secretome
BMC Endocrine Disorders
Adipose-derived stem cells
Adipocytes
Plasma
Secretome
Cytokines
Type 2 diabetes
title Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte’s secretome
title_full Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte’s secretome
title_fullStr Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte’s secretome
title_full_unstemmed Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte’s secretome
title_short Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte’s secretome
title_sort incretin based approaches for type 2 diabetes therapy effects on circulating cytokines and adipocyte s secretome
topic Adipose-derived stem cells
Adipocytes
Plasma
Secretome
Cytokines
Type 2 diabetes
url https://doi.org/10.1186/s12902-025-01999-w
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