Connexin-Based Therapeutics and Tissue Engineering Approaches to the Amelioration of Chronic Pancreatitis and Type I Diabetes: Construction and Characterization of a Novel Prevascularized Bioartificial Pancreas
Islet-containing SPECs secrete low levels of insulin and fail to respond to high glucose stimulation. Islets alone, SPECs without islets, and islet-containing SPECs pretreated with vehicle, 50 μM JM2, or 50 μM FFA were subjected to GSIS assay by first stimulating with low glucose (2.8 mM) for one hour and then high glucose (28 mM) for one hour. Buffer was collected at the end of both stimulation periods and analyzed for insulin by ELISA. (a) The concentration of insulin secreted per islet for all treatment groups. Two-way ANOVA revealed that there was significant pairing () and that glucose concentration and treatment were both significant sources of variation ( and , resp.). Bonferroni post hoc analysis determined that within the low glucose group free islets alone secreted significantly more insulin than any of the islet-containing SPEC treatments (, indicated on graph by ) and that, similarly, high glucose free islets secreted significantly more insulin than any of the high glucose islet-containing SPEC treatments (, indicated on graph by ). Paired -tests were used to compare high and low glucose conditions within treatment groups, and only free islets displayed a significant increase in insulin secretion upon high glucose stimulation (, indicated on graph by ). (b) The graph in (a) was limited to comparisons between islet-containing SPECs to better resolve the graph bars. No significant differences were observed. (c) The relative change in insulin secretion from low to high glucose stimulation. One-way ANOVA with Bonferroni post hoc analysis showed that the islets alone had a significantly increased relative change in insulin secretion compared to any of the SPEC treatment groups (). These data show that islet-containing SPECs secrete very low levels of insulin and that they are refractory to high glucose stimulation.
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