Protease Inhibition and Biological Distribution of the C Terminal Fragment of Adiponectin Receptor

Protease inhibition studies showed Adiponectin Receptor C- Terminal Fragment (AipoR CTF) inhibited insulin-degrading enzyme (IDE) and TNF alpha cleavage protease (TACE). Cleavage of Adiponectin Receptor by TACE to form CTF was demonstrated by western blot assays analysis of recombinate AdipoR1 treated with TACE and by inhibition studies. Tissue and blood analysis by standard immuno histochemistry (IHC) and immuno ctyochemistry (ICC) methods demonstrated CTF is primarily absorbed into the liver, pancreas and brain tissue where it is co-located with ide. CTF formation by TACE appears to occur in fat and muscle tissues and to be carried in circulation by an immunoglobulin bound form (Ig-CTF) that freely circulates and is immune cell bound in both blood and lymph nodes. Tissue from animal models showed levels of CTF increase with disease progression from non-diabetic to diabetic states. All of these data unveiled a novel regulation mechanism of AdiopR CTF in its free and Ig-associated forms which could impact insulin sensitivity and prevent insulin degradation by IDE in tissue and cells.