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No description available.

No description available.

No description available.

No description available.

Type 1 diabetes is an autoimmune disease in which patients' insulin-secreting beta cells in pancreatic islets are destroyed by their own immune system, leading to unregulated blood glucose levels and severe complications. Its only treatment is intensive insulin therapy, which carries the risk of hypoglycemic episodes and can result in seizures, coma, and even death. Islet transplantation has recently become an alternative, albeit experimental, treatment for type 1 diabetes patients. More than one donor graft is usually required to render recipients insulin independent, making the shortage of donor tissue an extremely important challenge in islet transplantation. Identifying the cell type that has the ability to differentiate into islet-like tissue is an important area of study. In this study, I hypothesized that insulin secreting human islet-like clusters could be generated from pancreatic ductal cells, a potential pancreatic progenitor cell type. Islet-like clusters were generated using crude exocrine tissue from human cadaveric donors. This crude exocrine tissue contained a large number of ductal cells, as well as other pancreatic cell types. To evaluate insulin secretion by human islet-like clusters, a static incubation system was set up and tested using Min6 cells, a known insulin-secreting cell line. Using static incubation, significant increases in insulin secretion by islet-like clusters were observed when the clusters were exposed to higher glucose levels and GLP-1, a known insulin secretagogue. Presence of corresponding C-peptide secretion demonstrated that de novo insulin secretion occurred. Furthermore, basal insulin secretion increased as culture stages progressed. An attempt was made to generate islet-like clusters using ductal cells purified by fluorescent activated cell sorting or magnetic activated cell sorting. Nevertheless, it was difficult to ensure survival and proliferation of purified ductal cells. Further studies will be necessary to confirm the role of ductal cells in the generation of islet-like clusters using the crude exocrine tissue, as well as to identify factors that can promote ductal cells proliferation after cell sorting.

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The Par6-polarity pathway regulates breast cancer metastasis, and more recently has been shown to regulate transforming growth factor β (TGFβ)-induced apoptosis. Integrins may mediate the regulation of TGFβ-induced apoptosis by Par6, as they are key regulators of cell polarity, survival and death. First, we confirmed that blocking Par6 activation significantly inhibits TGFβ-induced apoptosis in both monolayer and three-dimensional NMuMG (Normal Murine Mammary Gland) cell culture models. TGFβ altered the expression of β1 and β4 integrins in NMuMG monolayers. In addition, TGFβ significantly reduced the basal localization of α6 and β4 integrins in NMuMG three-dimensional acini-like structures (p < 0.001), which was dependent on both Par6 and TGFβ receptor I (TβRI)/SMAD activation. We went on to show that the activities of integrin pro-survival signaling mediators, NF-κB and FAK, were altered in response to TGFβ, and that blocking Par6 activation in the Par6/S345A mutant maintained polarity and basal α6 and β4 integrin expression in the presence of TGFβ in NMuMG three-dimensional structures, in addition to a significant increase in FAK activation. This suggests that TGFβ alters the expression, localization and downstream signaling of integrins, which may contribute to TGFβ-induced apoptosis

β-D-Glucan has been proposed to suppress appetite related perceptions thus contribute favourably to the regulation of energy intake and the increasing obesity problem in North America. Due to its low concentrations in grains, the challenge has been to produce β-glucan concentrates that can be incorporated into foods without adversely affecting product attributes. Therefore in the first part of the study, a protocol for the concentration of β-glucan, based on protein-polysaccharide incompatibility, was investigated. The extract obtained was utilized in the second part, where the effect of beverages with increased β-glucan content on perceived satiety and blood glucose, at different fibre concentrations was studied. Twenty nine healthy adults participated in this study. 5 beverage pre-loads, containing between 0-2.5 g of β-glucan in 500 mL of the sample, were ingested 120 min before the given meal. Results showed a trend towards a decrease in appetite scores with increasing β-glucan content of the beverages, as well as differences in the blood glucose readings, though these were not significant, and could not solely be attributed to β-glucan content due to differences in beverage composition.

The aim of this study was to understand the cellular mechanisms in enterocytes, which may decrease glucose uptake by viscous oat β-glucan. An in-vitro cell model examined the effect of diffusion limitation, fluid shear stimulation, and increased intestinal stretching. Mechanical stimulation of IEC-6 was assessed. A Flexcell Cell Streamer device applied different fluid flow stresses on cells. Flexcell FX-4000 was used for biaxial stretching of the cells. Following the confirmation of appropriate use of the cell model, the results indicated that high viscosity oat β-glucan might provide a physical barrier limiting diffusion of nutrients to the cells apical surfaces. Western blot analysis confirmed weak mechanical stimulation on the cells. Mechanical stimulation did not influence glucose uptake. Strain-induced cells showed lower activities in their glucose uptake. In conclusion, there may be a significant contribution of direct effects of the viscosity of oat β-glucan on cellular mechanisms of uptake in enterocytes.