The incidence of type 2 diabetes is considered an epidemic in Western countries, and its prevalence is more common in the Hispanic population than in non-Hispanic whites. Postprandial hyperglycemia has been associated with oxidative stress (OS), thus; reducing postprandial glycemia and/or OS through dietary consumption of resistant starch (RS) may be one approach to help modulate glucose and insulin responses. The purpose of this study was twofold: 1) to evaluate the physicochemical and sensory properties of cereal food products supplemented with RS. 2) to compare the effects of a single ingestion of granola bars with high (~18 grams of RS) and low (~0 grams of RS) RS compositions on the postprandial glucose and insulin responses (n=14) and oxidative stress parameters (cellular glutathione peroxidase, F2- isoprostanes, and oxygen radical absorbance capacity) in Hispanic women (n=9). Granola bars and cereals were developed to provide 2 levels (10% and 15%) of RS; isocaloric (0% RS) control samples were prepared with readily digestible (high amylopectin) starch. Samples were stored for up to 4 weeks at 20 °C. Mean composition of the high RS granola bars was 6% protein, 15% moisture, and 18% lipid. RS levels slightly increased from 14 to 16 g/serving after 4 weeks of storage, supporting published research that RS increases with storage due to retrogradation and crystallization of amylose chains. Color became lighter as the level of RS increased (p<0.001). Granola bars containing RS were less brittle (p=0.0043) than control granola bars. Sensory results indicated granola bars/cereals were acceptable. RS-supplemented granola bars were then used for the evaluation of RS ingestion in humans. There was no difference in postprandial glucose and insulin responses after a single ingestion of a RS-supplemented (18 g) granola bar. No differences were found in the oxidative stress parameters measured. In a subgroup of subjects (n=9), a lower glucose response 30 minutes after RS consumption was found (p=0.0496). Thus, RS consumption may lower fluctuations in blood glucose, which may help manage glucose levels in individuals at risk of type 2 diabetes. Further studies of short term RS consumption are warranted to elucidate its benefits in glucose management. / Ph. D.

Résumé : Chez toutes les cellules, une modulation précise de l’expression des gènes est essentielle afin de réguler adéquatement leur métabolisme et de s’adapter aux changements environnementaux. En effet, c’est l’expression des gènes, plutôt que la séquence d’ADN, qui détermine en grande partie la diversité et la complexité des organismes. Celle-ci dépend principalement des changements dans les niveaux d’ARNs cellulaires résultant de la modification de l’équilibre entre leurs taux relatifs de synthèse et de dégradation. Alors que la régulation transcriptionnelle a été largement étudiée par le passé, des études récentes révèlent que la stabilité de l’ARN joue aussi un rôle important dans le modelage du transcriptome. Toutefois, les mécanismes qui assurent la dégradation précise et sélective des ARNs sont globalement mal compris. Au cours de cette thèse, j’ai utilisé la ribonucléase III de levure Saccharomyces cerevisiae (Rnt1p) comme modèle pour étudier comment des transcrits spécifiques sont ciblés pour la dégradation et évaluer sa contribution à la régulation de l’expression génique. Les résultats indiquent que Rnt1p régule l’expression des gènes en utilisant une spécificité élargie pour des structures tige-boucles d’ARN. En effet, un nouveau motif structurel de Rnt1p permet la discrimination des tige-boucles ayant une séquence spécifique tout en bloquant la liaison à des hélices génériques d’ARN double-brin. D’un autre côté, l’identification des signaux de dégradation de Rnt1p à l’échelle du transcriptome a permis de révéler plus de 384 transcrits clivés par Rnt1p, dont la majorité sont des ARN messagers. En outre, l’impact de la délétion de RNT1 sur l’expression de ces gènes est influencé par les conditions de culture des cellules, ce qui suggère que Rnt1p est un important régulateur conditionnel de l’expression génique. Somme toute, les résultats présentés dans cette thèse démontrent comment des ARNs sont spécifiquement choisis pour la dégradation et soulignent l’importance de la dégradation nucléaire dans la régulation de l’expression génique en réponse à des changements environnementaux. // Abstract : Precise modulation of gene expression is essential for any cell in order to regulate its metabolism and adapt to environmental changes. In fact, it is gene expression, rather than DNA sequence alone, which mostly explains the functional diversity and complexity between the different cell types. As such, gene expression mainly results from changes in the levels of cellular RNAs which are, in turn, dependent on the equilibrium between their relative rates of synthesis and degradation. While transcriptional control has been largely studied in the past, recent publications reveal that changes in RNA stability also play an important role in shaping the transcriptome. Unfortunately though, the mechanisms ensuring precise and selective RNA degradation remains poorly understood. In this thesis, I have used the yeast Saccharomyces cerevisiae ribonuclease III (Rnt1p) as a model to study how specific transcripts are targeted for degradation and evaluate its contribution to the regulation of gene expression. The results indicate that Rnt1p regulates gene expression using a broad specificity for structured RNA stem loops. Indeed, a new structural motif of Rnt1p permits discrimination of hairpins with specific sequence while blocking the binding of the generic RNA duplexes recognized by other members of the RNase III family. This highly specific mode of substrate recognition was found to be easily modulated by a flexible network of protein RNA interactions. On the other hand, transcriptome-wide identification of Rnt1p degradation signals uncovered more than 384 transcripts, including 291 mRNAs. Interestingly, the impact of RNT1 deletion on mRNA expression is modulated by changes in the growth conditions of the cell, indicating that Rnt1p is an important regulator of conditional gene expression. Overall, the results presented in this thesis demonstrate how specific RNAs are selected for degradation and highlight the importance of nuclear RNA decay for fine tuning gene expression in response to changes in growth conditions.