ABSTRACT
Diabetes mellitus type 2 (T2D) is one of the metabolic disorders suffered by a global human being. Certain factors, such as lifestyle and heredity, can increase a person's tendency for T2D. Various genes and proteins play a role in the development of insulin resistance and ultimately diabetes in which one central protein that is discussed in this review is FoxO1. In this review, we regard FoxO1 activation as detrimental, promote high plasma glucose level, and induce insulin resistance. Indeed, many contrasting studies arise since FoxO1 is an important protein to alleviate oxidative stress and promote cell survival, for example, also by preventing hyperglycemic-induced cell death. Inter-relation to PPARG, another important protein in metabolism, is also discussed. Ultimately, we discussed contrasting approaches of targeting FoxO1 to combat diabetes mellitus by small molecules.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Forkhead Box Protein O1/physiology , Small Molecule Libraries/pharmacology , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/metabolism , Forkhead Box Protein O1/drug effects , Humans , Insulin Resistance , Oxidative Stress , PPAR gamma/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal TransductionABSTRACT
Diabetes is one of the most common metabolic diseases. Aside from the genetic factor, previous studies stated that other factors such as environment, lifestyle, and paternal-maternal condition play critical roles in diabetes through DNA methylation in specific areas of the genome. One of diabetic cases is caused by insulin resistance and changing the homeostasis of blood glucose control so glucose concentration stood beyond normal rate (hyperglycemia). High fat diet has been frequently studied and linked to triggering diabetes. However, most Asians consume rice (or food with high carbohydrate) and food with monosodium glutamate (MSG). This habit could lead to pathophysiology of type 2 diabetes mellitus (T2D). Previous studies showed that high-carbohydrate or high-MSG diet could change gene expression or modify protein activity in body metabolism. This imbalanced metabolism can lead to pleiotropic effects of diabetes mellitus. In this study, the authors have attempted to relate various changes in genes expression or protein activity to the high-carbohydrate and high-MSG-induced diabetes. The authors have also tried to relate several genes that contribute to pathophysiology of T2D and proposed several ideas of genes as markers and target for curing people with T2D. These are done by investigating altered activities of various genes that cause or are caused by diabetes. These genes are selected based on their roles in pathophysiology of T2D.
