心肌细胞自噬受损是2型糖尿病心肌病（DCM）的重要发病机制，但其调控机制尚未阐明。目前的研究均忽视了心脏作为一个整体，心脏主要细胞间的cross-talk。我们前期的研究表明胰岛素抵抗状态下心肌成纤维细胞和心肌细胞共培养可明显抑制心肌细胞自噬活性。通过分泌组学分析，我们发现胰岛素抵抗状态下心肌成纤维细胞分泌的CCN1明显增多，并且CCN1重组蛋白刺激可显著抑制心肌细胞自噬，但心肌成纤维细胞分泌CCN1是否可通过αvβ3/AKT/mTOR通路，抑制心肌细胞自噬体形成，并通过β-catenin/Rab7通路，抑制自噬体的成熟，从而架起心肌成纤维细胞与心肌细胞自噬之间的桥梁尚不清楚，本课题拟在细胞、动物及临床水平，深入探讨成纤维细胞分泌CCN1调控心肌细胞自噬，进而促进DCM发生发展的机制。研究结果将为DCM的防治提供新的靶点。

Impaired cardiomyocyte autophagy plays crucial roles in the pathogenesis of diabetic cardiomyopathy (DCM), however, the mechanism mediating autophagy in the DCM remains incompletely understood. At present, the mechanism of autophagy in cardiomyocytes did not include the cross-talk between the main cell types in the heart as a whole. Our previous studies have shown that co-culture of cardiac fibroblasts and cardiomyocytes in insulin resistance states can significantly inhibit cardiomyocyte autophagy. Secretomics revealed that in insulin resistance states, CCN1 secreted by cardiac fibroblasts increased, and we found CCN1 recombinant protein stimulation significantly inhibited cardiomyocyte autophagy. However, whether CCN1 secreted by cardiac fibroblasts could inhibit the formation of cardiomyocyte autophagosomes through the αvβ3/AKT/mTOR pathway, and inhibit the maturation of autophagosomes through the β-catenin/Rab7 pathway remain unclear. At levels of cell, animal and clinical patient, we aim to conduct systematic and in-depth exploration of the mechanism by which CCN1 regulate cardiomyocyte autophagy and further effect the progression of DCM. These results may provide new targets for prevention and cure of DCM.