Background/Aim: Hepatitis C virus infection is a known risk factor of impaired glucose metabolism and diabetes mellitus. Whether hepatitis B virus (HBV) infection is also associated with impaired glucose tolerance remains uncertain. The aim of the study was to conduct a systematic review on the association between HBV infection and impaired glucose metabolism Methods: Studies reporting the association between HBV infection and markers of impaired glucose metabolism were identified through keyword search in PubMed and Google Scholar. 10 studies (out of 320) were included in this systematic review. Results were included. Majority (n=7) of the included studies were conducted among the Asian populations. Of the 10 included studies, eight studies reported a significant association between HBV infection and impaired glucose metabolism, proxied by impaired glucose tolerance, impaired fasting glucose, diabetes mellitus, insulin resistance, and metabolic syndromes. The remaining two studies using diabetes mellitus and insulin resistance as outcome measures did not find a positive association with HBV infection. Conclusions: The association between HBV and impaired glucose metabolism is suggestive from the evidence compiled from included articles. However, whether the development of glucose intolerance or diabetes mellitus is linked to an infectious cause of HBV is still inconclusive. Further studies that could improve on the current understanding of the associations between HBV infection and impaired glucose metabolism are necessary. / published_or_final_version / Public Health / Master / Master of Public Health

Mammals have to adapt quickly to the changes of nutrition availability. The liver is the central organ that coordinates the responses to food deprivation upon fasting and nutrient overload during feeding. In liver, hormonal and nutrient pathways converge into the regulation of transcriptional programs that are involved in maintaining energy homeostasis. When these fine-tuned regulations in liver are altered due to constant surplus of nutrients or insufficient hormonal actions, multiple metabolic diseases including type II diabetes can occur, followed by severe complications. As a part of those regulatory programs, PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha) links hormonal signaling to the expression of glucose and lipid metabolic genes. Its transcriptional co-activator activity is tightly controlled via post-translational modification; GCN5 (histone acetyltransferase KAT2A) acetylates PGC-1alpha and suppresses its transcriptional activity, whereas Sirt1 deacetylates and activates PGC-1alpha. Herein, cyclin D1-CDK4 (cyclin-dependent kinase 4) kinase is identified as a new regulator of glucose metabolism in liver that modulates PGC-1alpha's transcriptional activity. Through a cell-based high throughput chemical screen, a CDK4 inhibitor was discovered to potently decrease PGC-1alpha acetylation. Cyclin D1-CDK4 kinase phosphorylates and activates GCN5, which then acetylates and inhibits PGC-1alpha activity on hepatic gluconeogenic genes. Feeding activates cyclin D1-CDK4 kinase in liver, which, in turn, suppresses glucose production independently of cell cycle progression. As part of the feeding response, insulin/GSK3beta (glycogen synthase kinase 3beta) signaling stabilizes cyclin D1 protein via sequestering cyclin D1 in the nucleus. In parallel, dietary amino acids increase hepatic cyclin D1 mRNA transcripts. Loss of hepatic cyclin D1 in mice leads to mild diabetic phenotypes. In diabetic models, cyclin D1-CDK4 is chronically elevated and refractory to fasting/feeding transitions; nevertheless further activation of this kinase normalizes glycemia. Thus, these findings show that hormonal and nutrient pathways utilize components of the cell cycle machinery in post-mitotic cells to control glucose homeostasis independently of cell cycle progression. / Chemistry and Chemical Biology

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published_or_final_version / abstract / toc / Chemistry / Master / Master of Philosophy

published_or_final_version / Chemistry / Master / Master of Philosophy

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

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Diabetes Mellitus is a common chronic disease that is an ever-increasing public health issue. Continuous glucose monitoring has been shown to help diabetes mellitus patients stabilize their glucose levels, leading to improved patient health. Hence, a glucose sensor, capable of continuous real-time monitoring, has been a topic of research for three decades. Current methods of glucose monitoring, however, require taking blood samples several times a day, hence patient compliance is an issue. Optical methods are one of the painless and promising methods that can be used for blood glucose predictions. However, having accuracies lower than what is acceptable clinically has been a major concern. To improve on the accuracy of the predictions, the signal-to-noise ratio in the spectrum can be increased, for which the use of thermally tunable vertical cavity surface emitting lasers (VCSELs) as the light source to obtain blood absorption spectra, along with a multivariate technique (Partial Least Square (PLS) techniques) for analysis, is proposed. VCSELs are semiconductor lasers with small dimensions and low power consumption, which makes them suitable for implants. VCSELs provide higher signal-to-noise ratio as they have high power spectral density and operate within a small spectrum. In the current research, experiments were run for the preliminary investigations to demonstrate the feasibility of the proposed technique for glucose monitoring. This research involves preliminary investigations for developing a novel optical system for accurate measurement of glucose concentration. Experiments in aqueous glucose solutions were designed to demonstrate the feasibility of the proposed technique for glucose monitoring. In addition, multivariate techniques, such as PLS, were customized for various specific purposes of this project and its preliminary investigation. This research will lead to the development of a small, low power, implantable optical sensor for diabetes patients, which will be a major breakthrough in the area of treating diabetes patients, upon successful completion of this research and development of the device.