Modulation of islet amyloid polypeptide induced β-cell toxicity and amyloid formation by serum albumin proteins.

Human islet amyloid polypeptide (hIAPP, also known as amylin) is a 37-residue neuropancreatic hormone implicated in the progression of type 2 diabetes. hIAPP is soluble and partially structured under physiological conditions, but misfolds to form amyloid deposits in the islets of Langerhans in type 2 diabetes. Along the misfolding pathway, hIAPP forms species that are toxic to pancreatic β-cells, resulting in decreased β-cell function and mass. Serum albumin proteins are a key component of blood plasma and interstitial fluids and are omnipresent in mammalian cell culture media. Immortalized β-cell lines are widely used as model systems for mechanistic studies of hIAPP-induced cytotoxicity and for screening potential inhibitors of hIAPP toxicity. The effects of bovine serum albumin (BSA), human serum albumin (HSA) and fetal bovine serum (FBS) on hIAPP cytotoxicity are examined and the effects of BSA and HSA on hIAPP amyloid formation are explored. The time required for IAPP to form amyloid is lengthened by sub stoichiometric concentrations of BSA and HSA. Cell permeability and cell viability assays with cultured INS 832-13 pancreatic β-cells reveal that BSA, HSA, and FBS reduce hIAPP cytotoxicity. Partial protection against treatment with 40 μM hIAPP is observed for serum albumin concentrations that are only one tenth (=3.75 μM) of the normal amount present in a regular complete cell media containing 10 % FBS. The implications for in vitro assays of hIAPP toxicity and studies of hIAPP amyloid inhibitors are discussed.