Hepatic inflammation and insulin resistance in pre-diabetes – further evidence for the beneficial actions of PPAR-γ agonists and a role for SOCS-3 modulation

Pre-diabetes is a condition affecting increasing numbers of the population who find themselves caught in the grey area between normal glucose regulation and diabetes mellitus and who experience impaired glucose tolerance or fasting glucose. The ability of thiozolidinediones (TZDs) to ameliorate the clinical signs of diabetes mellitus is well-known but there is also emerging evidence for the benefits of PPAR-gamma agonists in pre-diabetes. In this issue of the British Journal of Pharmacology, Collino and colleagues report that pioglitazone can reduce hepatic inflammation and insulin resistance in rats administered a high cholesterol and fructose diet. Furthermore, pioglitazone reduced the expression of suppressor of cytokine signalling (SOCS)-3 - considered to be a key link between inflammation and insulin resistance. Although much work remains to be performed in fully understanding how TZDs modulate the cellular mechanisms which underlie pre-diabetes, these findings provide preliminary evidence that administration of TZDs to pre-diabetics could be beneficial.