Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 155-165). Available also in a digital version from Dissertation Abstracts.

Thesis (Ph. D.)--University of Hong Kong, 1967. / Typewritten.

Une alimentation riche en protéines entraîne une importante diminution de la prise alimentaire, chez l’homme et l’animal, par rapport à une alimentation classique (riche en hydrates de carbones). Les précédents travaux du laboratoire chez le rat montrent que le mécanisme implique une induction de la production intestinale de glucose libéré dans la veine porte. Il s’ensuit un signal qui transite au cerveau via le nerf vague et se traduit par un effet anorexigène. Le régime protéique induit en fait une redistribution de la production endogène de glucose au profit du rein et de l’intestin chez le rat, et au profit de l’intestin et du foie chez la souris. L’effet anorexigène des protéines est présent également chez les souris, confirmant un rôle tout particulier de l’intestin, et du signal glucose portal, dans ce phénomène de satiété. Nos résultats montrent d’ailleurs que le signal glucose portal n’est pas impliqué dans l’augmentation de la production rénale de glucose induite par le régime protéique qui est observée uniquement chez le rat. Les mesures effectuées chez des rats nourris par différents régimes protéiques indiquent l’implication de mécanismes propres à la nature des protéines qui reste à déterminer. De plus nous avons mesuré une augmentation de la sensibilité à l’insuline de la production endogène de glucose chez le rat nourri par le régime protéique. Des études plus approfondies chez la souris devraient permettre de comprendre les mécanismes impliqués. Nos expériences suggèrent par ailleurs que le système mélanocortinergique ne serait pas impliqué dans l’effet anorexigène du régime à long terme mais pourrait constituer un élément important de contre-régulation face à l’hypophagie sévère temporaire provoquée par le changement de régime / Protein feeding is known to decrease hunger and subsequent food intake in animals and humans. Previous data point out the connection between the central nervous system and the intestinal glucose production in the central inhibitorycontrol of food intake by protein feeding. Our study demonstrates that protein feeding induces redistribution of endogenous glucose production to the kidney and intestine in rats and to the intestine and liver in the mouse. Anorexigenic effect of protein diet exists in both animal models, confirming a specific role of the intestine in this satiety phenomenon. Moreover, portal glucose sensing is not involved in the induction of renal glucose production by protein feeding that is only observed in rats. Measurement in rat fed with different protein diets suggest a role of the nature of the protein or structure, but proper mechanisms remain to be clarified. Moreover, protein feeding potentiates the endogenous glucose production suppression by insulin. Some additional studies have to be performed to find the mechanisms that are implicated. Our experiments suggest that the melanocortinergic system wouldn’t be involved in the longterm anorexigenic effect of protein feeding but could constitute an important counter-regulatory pathway against the temporary hypophagia induced by diet change

Recent research suggests that amino acids, such as leucine and isoleucine, can improve glucose tolerance in vivo and in vitro animal models by accelerating glucose uptake in peripheral tissues and stimulate glycogen synthesis in vitro in the absence of insulin. Our laboratory recently found that gavaging normal Sprague-Dawley rats with an amino acid mixture, composed of isoleucine, leucine, cystine, methionine, and valine, improved blood glucose response during an oral glucose challenge without an increase in the plasma insulin response. The blood glucose-lowering effect of the amino acid mixture was due to an increase in skeletal muscle glucose uptake. These results suggest that this amino acid supplement acutely improves muscle insulin sensitivity and blood glucose homeostasis. However, the effect of this amino acid mixture on glucose tolerance and muscle glycogen synthesis in humans has not been investigated. Some studies have also shown that daily supplementation or acute ingestion of amino acids may prevent muscle damage that occurs as a result of a prolonged, intense endurance exercise or strength training and therefore improves force production and exercise performance. However, the effects of the addition of an amino acid mixture to carbohydrate supplement on muscle damage after a prolonged endurance exercise, as well as on the subsequent anaerobic exercise performance, have not been characterized. Therefore, in this series of two studies, the effects of an amino acid mixture, composed of isoleucine, leucine, cyctine, methionine, and valine, on glucose tolerance, muscle glycogen resynthesis, muscle damage, and anaerobic exercise performance were investigated. Study 1 demonstrated that our amino acid mixture lowered the glucose response to an OGTT in healthy overweight/obese subjects in an insulin-independent manner. Study 2 demonstrated that both high and low dosages of amino acid mixture were effective in lowering blood glucose response to a carbohydrate bolus in athletes postexercise. High dosage of amino acid mixture was more potent in glucose regulation by providing a higher insulin response and amino acid effect. However, our amino acid mixture had no effects on post exercise muscle glycogen synthesis, exercise-induced muscle damage or subsequent anaerobic performance. Taken together, the results of this research series suggest that an amino acid mixture, composed of isoleucine and 4 additional amino acids, attenuates the glucose response to a glucose bolus in an insulin-independent manner, but does not enhance muscle glycogen restoration following exercise or prevent exercise-induced muscle damage. / text

Fibroblast Growth Factor (FGF) 21 is a liver-derived endocrine factor with multiple metabolic effects on glucose and lipid homeostasis in animals. The adipose tissue has been proposed as a major target of FGF21, where it enhances glucose uptake and modulates lipolysis as well as thermogenesis. However, the molecular mechanisms underlying the pleiotropic effects of FGF21 in adipocytes and the physiological roles of FGF21 in regulating energy homeostasis remain poorly characterized. Therefore, the present study aimed to investigate: 1) the signal transduction pathway whereby FGF21 enhances glucose uptake in white adipocytes; 2) the role of FGF21 in lipolysis in both mouse and human white adipose tissues (WAT) and its underlying mechanisms involved; 3) the phenotypes of FGF21 knockout (KO) mice with respect to energy expenditure and adiposity under both standard chow and high fat diet. Key findings: 1. In vitro studies demonstrated that extracellular signal-regulated kinases (ERK1/2) play an obligatory role in mediating FGF21-induced upregulation of glucose transporter-1 (GLUT1) expression and hence elevation of glucose uptake in 3T3-L1 adipocytes. 2. Chromatin immunoprecipitation assay revealed that Serum Response Factor (SRF) and ETS-like protein-1 (Elk-1), the two transcription factors which are known as the downstream targets of ERK1/2, were recruited to the endogenous GLUT1 promoter in adipocytes. A conserved binding motif for these two transcription factors was also identified in the GLUT1 promoter responsive to FGF21 stimulation in 3T3-L1 adipocytes by site-directed mutagenesis and luciferase assay. 3. In WAT of diet-induced obese mice, FGF21-evoked downstream signaling events, including the phosphorylation of ERK1/2 and SRF/Elk-1, the upregulation of GLUT1, and the increased glucose uptake, were markedly blunted compared to lean controls, suggesting the existence of “FGF21 resistance” in obesity. 4. In vivo and ex vivo studies on fasted wild type and FGF21 KO mice demonstrated that FGF21 acutely suppressed basal and forskolin-stimulated lipolysis in WAT. 5. FGF21-inhibited lipolysis was mediated by Akt-dependent reduction of cyclic adenosine monophosphate (cAMP) levels in both mouse and human WAT. 6. FGF21 KO mice were resistant to diet- and aging-induced obesity, which was attributed to decreased fat mass. The increased lipolysis and fatty acid oxidation in FGF21 KO mice may explain in part the lean phenotype of FGF21 KO mice. Conclusions: These results collectively suggest FGF21 as a key modulator of glucose and lipid metabolism in WAT, by activation of ERK1/2 kinase and Akt respectively. FGF21 and its signaling components may represent potential targets for the future development of new strategies for treating obesity and its medical complications. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Biochemistry / Master / Master of Philosophy

published_or_final_version / Biochemistry / Master / Master of Philosophy

No description available.

A derivatization method is applied to chemically modify the glucose molecules. Then the derivatized C1 and C2 labeled glucose can be differentiated by tandem mass spectrometry. A multiple reaction monitoring method is developed to quantify the C1- and C2-13C labeled glucose, with deuterated glucose as the internal standard.Based on the fragmentation of cross-linked amino acids (pyridinoline (PYD) and deoxypyridinoline (DPD)), a precursor ion scan method is developed to detect DPD and PYD from a complex matrix. DPD is detected in a hydrolyzed mouse ventricle collagen sample by this method.A series of peptides and proteins are successfully ionized by a home made DESI source. The investigation of the sample surface effect shows that self assembled monolayer surfaces produce better signal than bare gold surfaces, implying that this is due to the lower electron transfer on SAM film which allows more ions to survive.

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.