The aim of this study was to prepare biologically active insulin-loaded alginate microparticles by spray drying. Particles were produced from three alginate feed concentrations of 1, 1.5 and 2% w/v, with respective insulin loadings of 11.8, 7.8 and 5.8 mg/g of alginate and investigated in terms of mass yield, moisture content, particle size, morphology and encapsulation efficiency. The mass yield of the system was determined to be between 15 and 30%, with approximately 3% of the initial dry mass ending up in the exhaust filter. The moisture content of the particles was found to be between 4.9 and 11.1% and the mean size ranged between 1.2 and 1.6 μm. Particulate morphologies were observed to be mostly spherical with some ‘divots’ present on the surface. Lastly, the encapsulation efficiency determined by absorbance assay was approximately 40%. Particles produced from a 2% alginate feed were further assayed by determining the release of insulin in simulated gastrointestinal conditions and looking at the insulin and alginate distribution within spray dried particles. A steep release profile was observed in the first 120 min of the simulation in a gastric pH of 1.2 and a longer, more sustained release is observed in intestinal conditions, where an additional 20% of the total insulin in the particles is released over 600 min. Fluorescent labels revealed that insulin and alginate are concentrated towards the periphery of the particles. The residual bioactivity of insulin was assessed by an in vitro bioactivity assay, which was developed using Fast Activated Cell Based ELISA (FACE™) AKT kits specific for phosphylated AKT. The bioactivity of insulin in the particles after spray drying was determined to be 87.9 ± 15.3%. / Thesis (Master, Chemical Engineering) -- Queen's University, 2009-09-20 20:32:29.103

Cette etude pilote de six mois examinait si l'autogestion (AG) intensive par un agent secreteur d'insuline avait pour consequence une glycemie amelioree en comparaison avec une gestion standard (GS) chez les individus atteints de diabete de type 2. Des patients ont ete randomises soit a l'AG avec du repaglinide (n=8), ou du glyburide (n=6) ou a la GS (n=5). Des analyses biochimiques, alimentaires, comportementales, et d'activite physique ont ete effectuees. Les deux groupes de l'AG ont recu un enseignement d'autogestion en fonction du taux de glucose sanguin et une evaluation nutritionnelle qualitative. Le groupe AG (n=11) a suivi la cedule 65% du temps et a fait des ajustements 29% du temps. Une relation inverse significative a ete trouvee entre le changement de l'Alc et le pourcentage de temps d'ajustements accomplis correctement (r=0.64, p=0.035). La difference de masse corporelle entre l'AG et la GS n'etait pas significative, tout comme la masse corporelle moyenne a six mois. Une recherche plus approfondie avec un echantillon de plus grande taille serait necessaire afin d'explorer les avantages potentiels de la gestion du diabete via l'autogestion de medicaments oraux.

The objective of this study was to determine if teaching the new sugar guidelines, which now permit up to 10% of energy from added sugars, would modify dietary habits, metabolic control and perceived quality of life in free-living subjects with type 2 diabetes. In an eight month randomized controlled trial, 48 subjects with type 2 diabetes were taught, by a trained dietitian, either a conventional diabetic meal plan: conventional group (C) or one in which they could integrate the new sugar guidelines: sugar group (S). Patients were seen at the clinic every 2 months (total of 5 visits) by the dietitian and the endocrinologist. During the pre-randomization period (0 to 4 months) all subjects were taught the conventional diabetic diet and advised to avoid concentrated sugars. Randomization to the C or the S group took place at the 4 month visit (4 to 8 month period = post-randomization). The S group were taught how to use and integrate the Canadian Diabetes Association's new sugar choices (e.g. added sugar: honey, regular jam, white sugar, etc) into their daily diabetic meal plan. (Abstract shortened by UMI.)

No description available.

It is estimated that approximately 80% of all persons with DM2 are obese, and the prevalence of diabetes increases With increasing age and body weight. Intensive control resulting in near-normal glycemia in obese DM2 holds great potential for reducing morbidity and mortality, but is associated with weight gain. In turn, modest weight loss improves glycemia considerably. Current weight loss programs, with decreasing frequency of interventions over time, result in a weight loss pattern of a U-shaped curve indicating an inability in maintaining the lower weight. We hypothesized that increasing vs decreasing frequency of treatment visits over time would result in better weight loss and metabolic control. Forty-eight DM2 subjects (28 F, 20 M; wt = 98 +/- 3 kg; BMI = 35 +/- 2 kg/m2; DM duration = 11 +/- 8 yrs) were stratified according to weight and level of glycated hemoglobin (HbA1c), and randomized to one of two protocols: decreasing frequency (DF) of visits, seen weekly (for 2 mos), bimonthly (for 3 mos) and monthly (for 3 mos) and increasing frequency (IF) of visits seen in the reverse order. Visits included 18 lifestyle, behaviour modification, group sessions and 5 individual evaluations at 0, 2, 4, 8 and 12 months. (Abstract shortened by UMI.)

Feed efficiency and metabolism affect profitability of the various components of the beef industry by modulating distribution and use of nutrients within cattle. Separate studies were conducted to determine the 1) repeatability of feed efficiency measurements over time as beef heifers mature into cows, and 2) whether the production and regulation of glucose in heifers is affected by temperament. The influence of temperament on glucoregulatory hormones was studied in Angus crossbred heifers and Brahman heifers whose temperament was determined at weaning. The 6 most calm and 6 most temperamental heifers of each breed were fitted with jugular cannulas. Blood was collected at cannulation and then via the cannula during a 90-min rest period. Following 90 min, dextrose was infused (0.5 mg/kg BW) and blood samples were collected at specific intervals for 3 h total. In the crossbred heifers cortisol (P = 0.0560) and glucose (P = 0.0485) concentrations during the challenge were higher in temperamental relative to calm crossbred heifers. Insulin concentrations tended (P = 0.0737) to be higher in temperamental crossbred heifers. Cortisol (P = 0.0282) and glucose (P = 0.0011) concentrations were significantly higher in temperamental Brahman heifers. Insulin concentrations tended (P = 0.0793) to be greater for calm Brahman heifers. Temperamental cattle had a greater HPA axis response, which led to greater concentrations of cortisol and glucose, possibly because the glucose was being utilized differently by the temperamental cattle. Mature Brahman cow feed efficiency data was collected over two years, on two different cohorts of cows that had previous residual feed intake data as post-weaning heifers. In 2009 and 2010, 37 and 41 cows, respectively, in their first trimester of gestation were evaluated for RFI via the Calan gate system. Cows were fed 2.6% BW for 70 d with BW recorded weekly. Cows were classified according to their RFI values as either efficient or inefficient. Heifer RFI was not correlated to mature cow RFI based on assessment of the Pearson‟s correlation coefficient (r = -0.06, P = 0.57). This study indicates that establishment of RFI in heifers may not accurately predict their feed efficiency as mature cows.

No description available.

No description available.

The use of a bacterial expression system allowed the production and purification of PDX1 for <I>in vitro</I> phosphorylation analysis. This procedure allowed the purification of several forms of PDX1, some of which have never been reported previously. This study reiterates the fact that the activation of PDX1 and insulin gene transcription arises by a complex series of events, which are rapidly being unravelled, to provide greater insight as to how to obtain gene therapy treatments for diabetes mellitus.

Gene therapy, where non-islet cells are transduced to express insulin, encapsulated and implanted into the diabetic patient, is a possible alternative therapy for type I diabetes, which may alleviate some of the long-term complications of the disease. Insulin, however, is synthesised as a precursor, proinsulin, which is proteolytically modified by two endocrine-cell specific proteases, PC2 and PC3. Non-neuroendocrine cells do not express PC2 and PC3, but express a related protease, furin. Furin is unable to process proinsulin to insulin efficiently, so we employed PCR mutagenesis to alter the human preproinsulin cDNA around the normal processing sites, which when transcribed and translated yield cleavage sites recognised by furin. Wild type and mutant preproinsulin cDNAs were cloned into a mammalian expression vector under the control of the CMV promoter, and were expressed in the C2C12 and L6 myoblast cell lines and also the HepG2 liver cell line. Radioimmunoassays using an insulin specific antibody and an antibody that recognises proinsulin and insulin equally revealed that cells transfected with the wild type cDNA secreted 90% proinsulin whereas cells expressing the mutant cDNA secreted 75-90% processed insulin, suggesting more efficient processing of the mutant proinsulin by the endogenous furin. Further manipulation of the cDNAs linking them to the neomycin selection gene via an internal ribosome entry sequence (IRES), gave rise to stably transfected L6ins cell lines, expressing 2-10 ng/ml/24h total insulin-like immunoreactivity (ILI). With stable HepG2ins cells expressing in excess of 2.5 μg/5x10⁷ cells/24h mature, biologically active human insulin. These high expressing HepG2ins cells were implanted into BB/Edinburgh rates and strepozotocin treated nude mice.