Hypoadiponectinaemia in diabetes mellitus type 2: molecular mechanisms and clinical significance.

1. This review focuses on the regulatory mechanisms of adiponectin (APN) gene expression during physiologic conditions and both the clinical significance and underlying molecular mechanisms of hypoadiponectinaemia during pathologic conditions. 2. Adiponectin is a versatile cardiovascular protective factor. It plays an important role in regulating insulin sensitivity and energy homeostasis, with anti-inflammatory and anti-atherosclerotic properties. 3. Adiponectin gene expression is downregulated in both obesity and diabetes mellitus type 2. Hypoadiponectinaemia is an independent risk factor for coronary artery disease in type 2 diabetic patients. 4. Exogenous supplementation of recombinant APN attenuates insulin resistance, improving metabolic disorders. Therefore, APN-targeted pharmaceutical strategies increasing circulating APN levels may be therapeutic against type 2 diabetes. 5. There is great value in elucidating the regulatory mechanisms of APN gene expression during physiologic and pathologic conditions. APN biosynthesis regulation includes transcriptional expression and post-translational modification, oligomerization, and secretion. Under pathological conditions, including obesity and diabetes mellitus type 2, hypoxia, oxidative stress, and inflammation suppress APN mRNA levels and its secretion.