Cell and Biological Models for the C Terminal Fragment of Adiponectin Receptor

The impact of the peptides such as 32 amino acid peptide AdipoR1 C -terminal fragment (CTF) (AdipoR CTF344-374) can be studied in cell and animal models provided the conditions are defined for the biological system tested. In this work, calcium depleted cardiomyocytes (C2C12) were found useful as cell model for study of Ig-CTF formation and release. This cell model could be a useful tool for screening of compouns to block formation of CTF. A breast cancer cell model (SKBR-3) with labeled insulin was found useful for measurement of cellular loading and inhibition of insulin degradation. This cell model could be a useful tool for screening of compounds to block CTF inhibition of IDE. Leptin resistant rat models were shown to become hyper-insulinemic when treated with CTF allowing a model for inducing insulin resistance. The progression of leptin resistant rats to diabetes was measure-able by their oral glucose tolerance and plasma CTF levels. This animal model supported that AdipoR CTF raises intracellular plasma insulin but not glucose and is an important factor in diabetic progression. Together these models allow exploring formation and signaling of new inhibitory plasma peptides and demonstrate how to explore bioactivity of proteomic discoveries with cell and animal models.