Abstract:
Metabolic disease is a global concern, and the rate of its escalation is petrifying. Although
multiple pathophysiologies are regarded under the heading of metabolic diseases, Type 2
Diabetes Mellitus (T2DM) ranks to be one of the most threatening. Pouya Saeedi et al.
(2019) accounts prevalence of T2DM to rise from 520million cases (in 2030) to 630million
cases by 2045. Although the onset and progression of T2DM show a multi-faceted regulation, the conventional causative factors fail to account for this mounting threat. Thus, it stands imperative to look for newer unexplored, unconventional causative factors that could directly or indirectly influence the onset and progression of T2DM.
Human activities-induced release of xenobiotics across the environment intimates heavy
metal contamination as the upcoming threat over the orthodox causes. Reports highlight
Lead (Pb2+) as the looming endocrine & metabolic disruptor but does not provide any
additional comprehensions about its mode of action. At this juncture, this thesis
investigates and presents mechanistic understandings of Pb2+ induced metabolic
abnormalities. This study presents a comprehensive idea regarding Pb2+ induced pancreatic
β-cell dysfunction and T2DM occurrence in vivo. This study also explains Pb2+ induced
hepato-toxicity and fatty liver pathologies. Motivated with the non-nutrient (Pb2+) induced
pathophysiology of Non-Alcoholic Fatty Liver Disease (NAFLD), this study unveils a
definite mechanism of conventional high carbohydrate diet-induced NAFLD via ChREBP.
Taken together, this thesis dually targets T2DM by presenting a new credible “nonnutrient”
culprit and by discovering a novel mechanistic insight of hepatic dyslipidemia, which if targeted can indirectly encourage a reduction in hepatic pathologies linked to
T2DM aggravation.
