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.

In this thesis it is demonstrated that leptin and insulin hyperpolarise hypothalamic glucose responsive neurones via the activation of the large conductance ATP-sensitive (K_APT) channel. This channel was potassium selective, had a single channel conductance of 150 pS and channel activity was inhibited by micromolar tolbutamide and millimolar internal ATP. Brain cortical cell bodies and nerve terminals possess a large-conductance calcium-activated potassium (BK) channel. The nerve terminal BK channel switched from high to low activity modes, whereas cell body BK channel activity inactivates during depolarisation. Furthermore, BK channel inactivation was abolished by internal trypsin treatment, suggesting an inactivating particle was associated with the channel. Internal application of alkaline phosphatase irreversibly removed mode switching and inactivation of cortical BK channels. Blocking the cell body BK channel pore with 100 mM intracellular tetraethylammonium (TEA) prevented alkaline phosphatase removal of inactivation, indicating that the phosphatase site of action was located close to the pore. Finally, protein kinase A (PKA) increased the occurrence of the high BK channel activity mode whereas PKA retarded the full recovery of BK inactivation induced by hyperpolarisation. In a separate study it was demonstrated that stably expressed human brain BK (<I>hSlo</I>) channels inactivate in a trypsin-insensitive manner. This inactivation was not due to barium contamination, since 5 μM internal barium blocked <I>hSlo</I> channels only during strong depolarisations, yet inactivation was observed at less positive potentials. Furthermore co-expression of either <I>hSlo</I>β-1, or voltage-gated potassium (Kv) β1.1 or β2.1 subunits with the <I>hSlo</I> α-subunit did not affect the extent or rate of channel inactivation. Finally, the Kvβ-subunits moved the calcium and voltage curves of <I>hSlo</I> to more negative voltages and altered the activation and deactivation kinetics in a manner almost identical to that observed on co-expression of <I>hSlo</I>β-1 subunit with <I>hSlo</I> or by increasing the internal calcium concentration.