Islet transplantation is currently not a viable treatment option for Diabetes Mellitus patients. Achieving insulin-independence in a single patient requires large numbers of islets (>10,000 islets/kg body weight), and this, coupled with donor organ scarcity limits the therapeutic benefit of islet transplantation. Using peptide stimulants such as Exendin-4 to increase insulin output from pancreatic islets in response to elevated glucose levels could decrease the number of islets required to achieve normoglycaemia. Exendin-4 was conjugated to poly(vinyl pyrrolidone-co-acrylic acid) using a PEG3400 spacer (VAPE). Conjugation was confirmed using RP-HPLC. Exendin-4 content in VAPE was determined to be 30wt% using UV spectroscopy. Bioactivity was confirmed with a glucose challenge test using free islets. Islets were then encapsulated with or without VAPE in alginate/poly-L-Lysine microcapsules and subjected to a glucose challenge test every 48 hours for two weeks. Insulin secretion was quantified using radioimmunoassay techniques. When glucose levels changed from 2.8mM (basal level) to 16.8mM (elevated level), insulin secretion from free islets increased 300% (p=0.00009) when VAPE stimulant was present compared to control (no stimulant). Insulin secretion levels were not amplified at lower glucose levels (2.8mM-5.6mM) (p=0.87), the stimulatory effect was seen only at high glucose levels (16.8mM). Insulin secretion was comparable when free islets were stimulated with Exendin-4 peptide or VAPE (p=0.93) using equivalent concentrations ranging from 1nM to 1uM, indicating conjugation did not cause a dramatic loss of bioactivity. Insulin secretion was higher from islets encapsulated with VAPE relative to control after day 7, and remained significantly higher than the control through day 14 (p = 0.012). Although insulin secretion steadily decreased from control islets, insulin secretion remained constant from islets encapsulated with VAPE (p = 0.049). This study showed that encapsulating islets with VAPE was beneficial in maintaining insulin secretion from islets over 14 days, and preliminary results from ongoing experiments indicate this benefit may extend to four weeks or longer. Using this conjugate could be an effective way to decrease the number of islets required for a single transplantation.