Adipose tissue derived-factors impaired pancreatic β-cell function in diabetes

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2018-10, Vol.1864 (10), p.3378-3387
• Main Authors: Rebuffat, Sandra A., Sidot, Emmanuelle, Guzman, Caroline, Azay-Milhau, Jacqueline, Jover, Bernard, Lajoix, Anne-Dominique, Peraldi-Roux, Sylvie
• Format: Article
• Language: English
• Subjects: Adipose Tissue - metabolism; Animals; Apoptosis; Biochemistry, Molecular Biology; Cell Line; Cell Proliferation; Chemokines - metabolism; Culture Media, Conditioned - chemistry; Diabetes Mellitus, Type 2 - metabolism; Disease Models, Animal; Endocrinology and metabolism; Genomics; Human health and pathology; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Life Sciences; Macrophages - metabolism; Male; Obesity - complications; Obesity - metabolism; Pancreatic islets; Peri-pancreatic adipose tissue; Rats; Rats, Zucker; Type 2 diabetes; ZDF rat
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2018.07.024

Inflammatory factors produced and secreted by adipose tissue, in particular peri-pancreatic adipose tissue (P-WAT), may influence pancreatic β-cell dysfunction. Using the ZDF Rat model of diabetes, we show the presence of infiltrating macrophage (ED1 staining) on pancreatic tissue and P-WAT in the pre-diabetes stage of the disease. Then, when the T2D is installed, infiltrating cells decreased. Meanwhile, the P-WAT conditioned-medium composition, in terms of inflammatory factors, varies during the onset of the T2D. Using chemiarray technology, we observed an over expression of CXCL-1, -2, -3, CCL-3/MIP-1α and CXCL-5/LIX and TIMP-1 in the 9 weeks old obese ZDF pre-diabetic rat model. Surprisingly, the expression profile of these factors decreased when animals become diabetic (12 weeks obese ZDF rats). The expression of these inflammatory proteins is highly associated with inflammatory infiltrate. P-WAT conditioned-medium from pre-diabetes rats stimulates insulin secretion, cellular proliferation and apoptosis of INS-1 cells. However, inhibition of conditioned-medium chemokines acting via CXCR2 receptor do not change cellular proliferation apoptosis and insulin secretion of INS-1 cells induced by P-WAT conditioned-medium. Taken together, these results show that among the secreted chemokines, increased expression of CXCL-1, -2, -3 and CXCL-5/LIX in P-WAT conditioned-medium is concomitant with the onset of the T2D but do not exerted a direct effect on pancreatic β-cell dysfunction.