Low proliferative potential of adipose-derived stromal cells associates with hypertrophy and inflammation in subcutaneous and omental adipose tissue of patients with type 2 diabetes mellitus
| Autor: | S. Michurina, E. I. Ratner, Ekaterina A. Shestakova, N. Podkuychenko, Ye. V. Parfyonova, I. S. Stafeev, A. Panevina, Yuriy Ivanovich Yashkov, Marina Vladimirovna Shestakova, Mikhail Menshikov, V. Fedenko, Igor A. Sklyanik, Alexander V. Vorotnikov, Kamil Yahyaev |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism Abdominal Fat Subcutaneous Fat Adipose tissue 030209 endocrinology & metabolism Inflammation 030204 cardiovascular system & hematology Carbohydrate metabolism Muscle hypertrophy 03 medical and health sciences 0302 clinical medicine Endocrinology Insulin resistance Internal medicine Diabetes mellitus Internal Medicine medicine Humans Obesity Cells Cultured Cell Proliferation business.industry nutritional and metabolic diseases Type 2 Diabetes Mellitus Mesenchymal Stem Cells Hypertrophy Middle Aged medicine.disease Adipose Tissue Diabetes Mellitus Type 2 Case-Control Studies Female Insulin Resistance medicine.symptom Adipocyte hypertrophy business Omentum |
| Zdroj: | Journal of Diabetes and its Complications. 33:148-159 |
| ISSN: | 1056-8727 |
| DOI: | 10.1016/j.jdiacomp.2018.10.011 |
| Popis: | Background Obesity and type 2 diabetes mellitus (T2DM) are among the most important morbidity factors. In this study we tested the hypothesis that low proliferative potential of adipose derived stromal cells (ADSC) associates with reduced formation of new fat depots, excess accumulation of fat in the functional adipocytes and their hypertrophy, resulting in fat inflammation and insulin resistance. Methods We screened two groups of obese patients with or without T2DM, matched for BMI, age, and duration of obesity to test the hypothesis that hypertrophy and decreased renewal of adipocytes may underlie transition from obesity to T2DM. All patients were matched for carbohydrate metabolism (fasting blood glucose level, glycated hemoglobin, HOMA-IR index and M-index). The subcutaneous and omental fat tissue biopsies were obtained during bariatric surgery from obese individuals with or without T2DM. The morphology and immunophenotype of subcutaneous and omental fat was assessed in frozen tissue sections. ADSC were isolated from both types of fat tissue biopsies and screened for morphology, proliferative potential and inflammatory status. Results The non-diabetic patients had normal carbohydrate metabolism and moderate insulin resistance measured by HOMA-IR and hyperinsulinemic clamp (M-index), while T2DM patients were extremely insulin resistant by both indexes. The average size of diabetic adipocytes was higher than that of non-diabetic in both subcutaneous and omental fat tissues, indicating adipocyte hypertrophy in T2DM. Both these tissues contained higher level of macrophage infiltration and increased M1-like to M2-like ratio of macrophage subpopulations, suggesting increased fat inflammation in T2DM. This was confirmed by increased activatory phosphorylation of stress-induced JNK1/2 in diabetic ADSC. Conclusion These results suggest that blunted proliferation and increased hypertrophy of diabetic ADSC may lead to reduced insulin sensitivity via increased inflammation mediated by M1 macrophages and JNK1/2 pathway. |
| Databáze: | OpenAIRE |
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