This daily diary study investigated the emotional experiences and relationship behaviors of married couples coping with the husband's Type 2 diabetes, and how those experiences and behaviors affected his blood glucose levels. Repeated measures multilevel models examined the effects of husbands' and wives' absolute levels of positive and negative emotional experiences, balance of positive to negative emotional experiences, absolute levels of positive and negative behaviors, and balance of positive to negative behaviors on husbands' glucose. Husbands' negative emotional experience and wives' positive balance of relationship behaviors predicted lower blood glucose levels. For husbands who were younger, in poorer general health, and whose wives were more satisfied with their marriage, husbands' positive emotional experience predicted lower blood glucose levels. For husbands in better general health, wives' reports of a higher balance of positive as opposed to negative emotional experience also predicted lower blood glucose levels. Overall, results indicate that positive emotional experience and a balance of emotional experience and relationship behavior that is predominantly positive predicts positive diabetes outcomes as measured by lower daily blood glucose levels.

Improved insulin sensitivity and glucose tolerance may be attributable to vitamin D sufficiency. An experimental design was created to investigate the use of phototherapy to increase serum vitamin D levels and improve circulating blood glucose levels in pre-diabetics. Seven participants with a pre-diabetic condition were randomly allocated to either 3 months of phototherapy or no therapy. OGTT, HbA1c, and serum vitamin D levels were assessed before and after treatment. In 2 treatment participants, pre-diabetes status was reduced from combined IFG/IGT to iIFG in one and iIGT in the second, while 1 control participant developed combined IFG/IGT and another, type 2 diabetes. HbA1c values improved in the phototherapy group but not in the controls. Phototherapy also increased serum vitamin D levels in the treatment group but not in the controls. This pilot study suggests that the experimental protocol was effective and it should be implemented in a larger sample size to confirm those trends.

The high affinity sodium/glucose cotransporter (SGLT1) couples transport of Na+ and glucose. Investigation of the structure/function relationships of the sodium/glucose transporter (SGLT1) is crucial to understanding co-transporter mechanism. In the first project, we used cysteine-scanning mutagenesis and chemical modification by methanethiosulphonate (MTS) derivatives to test whether predicted TM IV participates in sugar binding. Charged and polar residues and glucose/galactose malabsorption (GGM) missense mutations in TM IV were replaced with cysteine. Mutants exhibited sufficient expression to be studied in detail using the two-electrode voltage-clamp method in Xenopus laevis oocytes and COS-7 cells. The results from mutants T156C and K157C suggest that TM IV participates in sugar interaction with SGLT1. This work has been published in Am J Physiol Cell Physiol 295 (1), C64-72, 2008. The crystal structure of Vibrio parahaemolyticus SGLT (vSGLT) was recently published (1) and showed discrepancy with the predicted topology of mammalian SGLT1 in the region surrounding transmembrane segments IV-V. Therefore, in the second project, we investigated the topology in this region, thirty-eight residues from I143 to A180 in the N-terminal half of rabbit SGLT1 were individually replaced with cysteine and then expressed in COS-7 cells or Xenopus laevis oocytes. Based on the results from biotinylation of mutants in intact COS-7 cells, MTSES accessibility of cysteine mutants expressed in COS-7 cells, effect of substrate on the accessibility of mutant T156C in TM IV expressed in COS-7 cells, and characterization of cysteine mutants in TM V expressed in Xenopus laevis oocytes, we suggest that the region including residues 143-180 forms part of the Na+- and sugar substrate-binding cavity. Our results also suggest that TM IV of mammalian SGLT1 extends from residue 143-171 and support the crystal structure of vSGLT. This work has been published in Biochem Biophys Res Commun 378 (1), 133-138, 2009 Previous studies established that mutant Q457C human SGLT1 retains full activity, and sugar translocation is abolished in mutant Q457R or in mutant Q457C following reaction with methanethiosulfonate derivatives, but Na+ and sugar binding remain intact. Therefore, in the third project, we explored the mechanism by which modulation of Q457 abolishes transport, Q457C and Q457R of rabbit SGLT1 expressed in Xenopus laevis oocytes were studied using chemical modification, the two-electrode voltage-clamp technique and computer model simulations. Our results suggest that glutamine 457, in addition to being involved in sugar binding, is a residue that is sensitive to conformational changes of the carrier. This work has been published in Biophysical Journal 96 (2), 748-760, 2009. Taken together our study along with previous biochemical characterization of SGLT1 and crystal structure of vSGLT, we propose a limited structural model that attempts to bring together the functions of substrate binding (Na+ and sugar), coupling, and translocation. We propose that both Na+ and sugar enter a hydrophilic cavity formed by multiple transmembrane helices from both N-terminal half of SGLT1 and C-terminal half of SGLT1, analogous to all of the known crystal structures of ion-coupled transporters (the Na+/leucine transporter, Na+/aspartate transporter and lactose permease). The functionally important residues in SGLT1 (T156 and K157 in TM 4, D454 and Q457 in TM 11) are close to sugar binding sites.

Glucose is the primary metabolic signal reflecting the current energy state of the body. Glucose influences the excitability of neurons in the area postrema (AP), a circumventricular organ (CVO), prompting my interest in investigating whether the subfornical organ (SFO), another sensory CVO can also detect glucose. Using patch-clamp electrophysiology, we investigated the influence of changing glucose concentrations on the excitability of SFO neurons. In dissociated SFO neurons, altering the bath concentration of glucose (1mM, 5mM, 10mM) influenced the excitability of 49% of neurons tested (n=67). Glucose-inhibited (GI, hyperpolarized by increased glucose or depolarized by decreased glucose) and glucose-excited (GE, depolarized by increased glucose or hyperpolarized by decreased glucose) neurons were observed. GI neurons (27%, n=18) depolarized in response to decreased glucose (n=10, mean 4.6 ± 1.0 mV) or hyperpolarized in response to increased glucose (n=8, mean -4.4 ± 0.8 mV). In contrast, GE neurons (22%, n=15) depolarized in response to increased glucose (n=9, mean 6.4 ± 0.4) or hyperpolarized in response to decreased glucose (n=6, mean -4.8 ± 0.6 mV). These data show that glucose acts on a subpopulation of SFO neurons to produce both excitatory and inhibitory actions. Using voltage-clamp recordings two groups of SFO neurons were identified: those producing an outward current (GI) and those producing an inward current (GE) in response to increasing concentrations of glucose from 1 to 10 mM (n=23). The mean glucose-induced inward current had a reversal potential of -24 ± 12 mV (mean input resistance 2.0 ± 0.4 GΩ, n= 5), suggesting it may be mediated by a NSCC. The mean glucose-induced outward current (mean input resistance 1.7 ± 0.3 GΩ, n=7) had a mean reversal potential of -78 mV ± 1.2 mV (n = 5), suggesting it may be mediated by an activation of either K+ or Cl-current (ECl = -67 mV, EK = -89 mV). The SFO has projections to the PVN, a regulator of energy balance. I investigated the effects of increasing concentrations of glucose (1 to 10 mM) on the membrane potential of dissociated SFO neurons projecting to the PVN. Thirty percent of SFO-PVN neurons tested (n=10) responded with membrane hyperpolarizations (mean -4.2 ± 0.8 mV, n=3) suggesting a proportion of these cells are GI neurons. These data indicate that SFO neurons are glucose-responsive, which supports a role for the SFO as a regulator of energy balance. / Thesis (Master, Physiology) -- Queen's University, 2009-09-24 20:20:33.319

No description available.

No description available.

Dietary carbohydrate during pregnancy is essential but whether this requirement is specific to glucose or if fructose could substitute for glucose in the diet of pregnant rat dams was investigated. It was concluded that the carbohydrate requirement for the rat during pregnancy is not specific to glucose and the level, not the type, of carbohydrate was critical. The potential toxicity of high fructose diets was also investigated. Dams fed high fructose had significantly higher liver weights than dams fed high glucose while other toxic indicators were not affected. A third aspect was the comparison of isocaloric, low carbohydrate diets containing different sources of 4% glucose equivalents: glucose, fructose or lipid-glycerol. Fructose and lipid-glycerol were not adequate substitutes for glucose. The measurement of amniotic fluid glucose, which increased as either dietary glucose or fructose increased in the maternal diet may be a new, accessible nutritional indicator of carbohydrate status.

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.