Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: the significance of transthyretin.

Retinol-binding protein 4 (RBP4) is the principle carrier of retinol in the human plasma, which circulates as a complex with transthyretin (TTR), a homotetrameric thyroxine transport protein. Although this complex formation is thought to prevent glomerular filtration of RBP4, it also stabilizes the quaternary structure of TTR. Recent studies indicate elevated plasma levels of RBP4 in type 2 diabetes (T2D). In contrast, reduced RBP4 levels were observed in type 1 diabetes (T1D). Herein, we critically examine the probable mechanisms involved in the regulation of RBP4 and TTR levels during T2D and T1D. The available evidences point to the involvement of pancreatic factors in regulating the expression of both RBP4 and TTR. It appears that during T1D, TTR levels are reduced and it exists predominantly as a monomer that may interfere its interaction with RBP4 resulting in its loss through glomerular filtration. However, plasma TTR levels remain high under T2D conditions and thus reducing glomerular filtration of RBP4. Therefore, the plasma TTR levels appear to be an important determinant of plasma RBP4 levels in these two diabetic conditions.