No description available.

No description available.

Background: Type 2 diabetes mellitus is a metabolic disorder characterized by the rise of fasting plasma glucose from its normal range (≥125mg/dl). It is marked by insufficient production of insulin from pancreatic β-cells as a result of failed compensation due to insulin resistance. Several treatments are available for the disorder, which mainly focus on improving the sensitivity of insulin in different body tissues. Recently, probiotics were suggested as candidate treatments for type 2 diabetes and for extending lifespan as well. This experiment aims to investigate such claims using Drosophila melanogaster as a disease model.   Results: Other than the observed low average weights in treated larva samples, probiotics did not show any other significant results in affecting the length, glucose, glycogen, and trehalose levels (One-Way ANOVA and Kruskal-Wallis, p>0.05). Real-time PCR was only carried out once. Thus, no statistical tests were reliable enough to analyse the data obtained. The longevity study, on the other hand, did show significance (Log-rank (Mantel-Cox) test and Gehan-Breslow-Wilcoxon test, p<0.0001), as the probiotic Bifidobacterium lactis extended the lifespan of adult flies feeding on a high sugar diet significantly when compared to the control ones feeding on only high sugar diet without probiotics.   Conclusion: Except for weight measurements, none of the other results was reliable enough to make a concrete conclusion on whether the treatments indeed worked in reversing type 2 diabetes symptoms or not. Real-time PCR results did show some effects of some of the treatments at different developmental stages. However, unless Real-time PCR is repeated at least once using the same protocol, no deduction can be made. Additionally, the data obtained hint that the dosage used (0.025 g) was too high for larvae and adult flies and might have caused malnutrition by blocking their midgut and decreasing food absorption. Hence, false significant or non-significant results were acquired instead.   Further studies are required using a much lower probiotic dosage if Drosophila is used as a disease model. Although, other models such as mice or rats are recommended in this case, in order to reach a solid conclusion about the effectiveness of probiotics in treating type 2 diabetes mellitus. Baring these thoughts in mind and based on the results of this experiment, the null hypothesis indicating that there is no significant relationship between the use of probiotics and reversing type 2 diabetes mellitus symptoms is therefore accepted.

No description available.

Aging is the major risk factor for chronic age-related diseases characterized by loss of homeostasis, organ dysfunction, and inflammation. Calorie restriction (CR) has been shown to slow aging and delay the onset of chronic age-related diseases. Even though CR has many positive health effects, the degree and duration of the restriction needed would reduce the intervention's usefulness and make it challenging to start and maintain in humans. The difficulties brought on by CR have led to the development of CR mimetics that can mimic the effects of CR without reducing food intake (in an ad libitum state). We hypothesize that in PEPCK bovine Growth Hormone (bGH) overexpressing transgenic mice with accelerated metabolic and cognitive aging, the health span and phenotypes of aging can be improved by adding CR mimetics, a combination of lipoic acid, nicotinamide, thiamine, pyridoxine, and piperine to the diet. From 10 to 40 weeks of age, bGH-tg mice and their normal (N) littermates were fed CRM diet ad libitum. Normal littermates and bGH-tg mice fed a standard chow diet served as controls. Evaluation of the effects of CRM included insulin and glucose tolerance tests (ITT and GTT), indirect calorimetry as well as rotarod, working memory, grip strength testing. Body weight and percent fat mass were significantly lower, but percent lean mass was significantly higher in mice on a CRM diet at 40 weeks. At 19 weeks, insulin sensitivity was improved considerably in treated N and bGH-tg males. At 20 weeks of age, all mice on a CRM diet had significantly improved glucose tolerance and lower fasting glucose. At week 32, treated N female mice had significantly higher energy expenditure during the day and night per gram of body weight. In treated N males, this was true only during the day. Male bGH-tg mice on CRM diet had decreased energy expenditure during the night. Insulin sensitivity was significantly improved in treated male N and bGH-tg mice at week 37. Week 38 GTT showed enhanced glucose tolerance and lower fasting glucose in all mice on a CRM diet except Tg females. Week 39-40 Y-maze, rotarod and grip strength testing showed improved motor coordination and grip strength in all mice on CRM diet with no difference in working memory. Also, there was a significant improvement in metabolic and aging phenotype with lowered pro-inflammatory cytokines at the gene and protein levels in various tissues. Our study indicates the employed CRM produce the beneficial health effects in short-lived, insulin resistant bGH Tg mice but the effects are time-, sex-, genotype-, and diet-dependent. Most of the effects of this intervention resemble the effects of CR suggesting that employed compounds may act via similar mechanisms. This work was funded by the SIU-SOM Geriatrics Research Initiative (AB), NIA R01AG068288, and the Hillblom Foundation (PK).

Lors d'un exercice physique prolongé, les muscles produisent et libèrent de l'interleukine-6 (IL-6). Cette production est corrélée à l'intensité de l'exercice et à la baisse des réserves musculaires en glycogène. L'IL-6 agirait par voie endocrine en favorisant la production endogène de glucose par le foie.<br />Notre premier objectif était d'étudier le contrôle de l'expression du gène IL-6 dans le muscle squelettique à l'exercice chez le rat et plus particulièrement l'importance de la voie de signalisation de la calcineurine, activée par la contraction musculaire. Nous avons d'abord montré que la transcription du gène IL-6 avait lieu dans les fibres musculaires oxydatives (I et IIa) et était associée à une activité importante de la voie de la calcineurine. Nous avons ensuite montré que l'administration d'inhibiteurs pharmacologiques de la calcineurine (ciclosporine A ou FK506) diminuait significativement la transcription du gène IL-6 dans les muscles lents/oxydatifs, prévenant ainsi l'apparition de la protéine dans le plasma. Nous avons ainsi démontré l'implication de la voie de la calcineurine dans le contrôle du gène codant IL-6 dans le muscle en réponse à un exercice unique. <br />Notre deuxième objectif était d'étudier l'action d'IL-6 sur le foie à l'exercice, plus particulièrement sur le contrôle du gène codant une enzyme clé de la néoglucogenèse, la phosphoenolpyruvate carboxykinase (PEPCK). Nous apportons des arguments expérimentaux en faveur d'un effet direct d'IL-6 sur le tissu hépatique et d'un contrôle possible de la transcription du gène codant PEPCK par l'IL-6 circulante. D'autre part nous suggérons l'implication d'acteurs moléculaires nouveaux, Peroxisome proliferator-activated receptor γ coactivator alpha (PGC-1α) et Farnesoid X receptor (FXR), dans le contrôle de la néoglucogenèse à l'exercice.

Overexpression of Phosphoenolpyruvate carboxykinase - cytosolic (PEPCK, encoded by Pck-1 gene) has been found to be associated with the prevalence of hyperglycemia in Type 2 Diabetes Mellitus (T2DM) patients. The Pck-1 enzyme catalyzes the rate limiting step in endogenous glucose production. The aims of this study are to develop a Pck-1:eGFP reporter zebrafish and validate it as a potential tool for the screening of novel anti-diabetic compounds. 3.6 kb zebrafish Pck-1 promoter fragment was cloned and a Pck-1:eGFP expression vector was constructed. After DNA microinjection, we generated Pck-1:eGFP reporter zebrafish with strong eGFP expression in developing liver. Validation studies confirmed that Pck-1:eGFP zebrafish embryos responded to treatment of glucose, cAMP and dexamethasone, metformin and rosiglitazone similarly to that of humans. This novel Pck-1:eGFP reporter fish line can serve as a tool for the screening and development of novel anti-diabetic drugs that may have potential in the treatment of T2DM.

Overexpression of Phosphoenolpyruvate carboxykinase - cytosolic (PEPCK, encoded by Pck-1 gene) has been found to be associated with the prevalence of hyperglycemia in Type 2 Diabetes Mellitus (T2DM) patients. The Pck-1 enzyme catalyzes the rate limiting step in endogenous glucose production. The aims of this study are to develop a Pck-1:eGFP reporter zebrafish and validate it as a potential tool for the screening of novel anti-diabetic compounds. 3.6 kb zebrafish Pck-1 promoter fragment was cloned and a Pck-1:eGFP expression vector was constructed. After DNA microinjection, we generated Pck-1:eGFP reporter zebrafish with strong eGFP expression in developing liver. Validation studies confirmed that Pck-1:eGFP zebrafish embryos responded to treatment of glucose, cAMP and dexamethasone, metformin and rosiglitazone similarly to that of humans. This novel Pck-1:eGFP reporter fish line can serve as a tool for the screening and development of novel anti-diabetic drugs that may have potential in the treatment of T2DM.