A recent observation from experimental, clinical and genetic evidence suggests endoplasmic reticulum was responsible for molecular mechanism of gluco-lipotoxicity which may contribute to ß - cell dysfunction in type II diabetes [8, 9]. In this review, we discussed about the involvement of ER in gluco-lipotoxicity induced ß- cell dysfunction along with the brief involvement of mitochondria. ER stress response Adaptation to metabolic changes requires the high regulation and co-ordination of many homeostatic systems, since the quality and quantity of available nutrients does not temporally match their needs. Pancreatic ß - cells displaying remarkable response to nutrients by the balance between the anabolic hormone insulin and the catabolic hormone glucagon in order to maintain fuel homeostasis. For an appropriate response, the cells require the development of suitable sensors and signaling molecules, which integrates all these signals into an appropriate insulin secretory rate in order to maintain homeostasis.
Unveiling the genetic and biochemical connection has helped patients and common people to realize that obesity is a serious condition comparable to coronary risk, stroke and cancer. (Farooqi & O’... ... middle of paper ... ...roguel, 2009). Conclusion Obesity is more complex than it was thought to be. It is heterogeneous in terms of genotype and phenotype. That is, obese individuals differ greatly in their fat deposition patterns, genes that cause them and associated factors.
Glycation is a natural chemical reaction in the body that involves combining sugar molecules to protein molecules without the help of enzymes. In contrast to similar a chemical reaction that involves enzyme-directed processes called glycosylation, glycation disrupts normal metabolic pathways. This results in the production of advanced glycation end products (AGEs), which are assocated with oxidative damage that leads to pathological changes in various organ systems. AGEs and Chronic Disease The 'normal' American diet usually contains a lot of high-sugar, high-fat foods that have been associated with the development of chronic diseases such as diabetes and heart disease. Just how these processes come about can be explained in the molecular and cellular level by the formation of AGEs.
Some studies have supported the hypothesis that insulin resistance develops from metabolic inflexibility due to decreased fat oxidation and accumulation of cytosolic lipid molecules (Koves et al., 2008). However, increasing amounts of recent studies have presented observations that point to excessive, not diminished, incomplete beta-oxidation is the true cause of obesity-related insulin resistance in skeletal muscle (Koves et al., 2008). In addition, Koves et al. (2008) also revealed that insulin resistance is related to metabolic inflexibility during the fasted-to-fed transition as well as the depletion of organic acid intermediates from the citric acid cycle (Koves et al., 2008). Despite disagreeing on the precise cause of insulin resistance, all of the published research agrees on one central theme: it is imperative to remain metabolically flexible in order to avoid the numerous, and potentially disastrous, consequences associated with metabolic inflexibility.
MicroRNA and Liver One of the major organs that plays an important role in maintaining the glucose balance is the liver. Down regulation of microRNAs in the liver results in impairment of hepatic homeostasis which results in diabetes. Sekine et al. showed that liver cell specific Dicer1 knockout mice displayed impaired blood glucose control and hepatic steatosis (44). The expression of microRNA-122, microRNA-148a, microRNA-192, and microRNA-194 was down-regulated in liver cells of Dicer1 knockout mice (45, 46).
Metabolic syndrome is described to be a cluster of metabolic risk factors that combines together to create a single individual health issue. The individual factors that combined to create this issue are insulin resistance, hypertension which is a form of high blood pressure, cholesterol abnormalities, impaired glucose tolerance, the tendency to develop fat around the abdomen and an increased risk for clotting. The metabolic disorders and cardiovascular disease are very close related. This syndrome is considered to be a risk factor for several cardiovascular diseases and type 2 diabetes that arises due to insulin resistance and an abnormal function and pattern of body fat. Insulin resistance refers to the diminished ability of cells to respond to the action of insulin in promoting the transport of the sugar glucose, from blood into muscles and other tissues.
Furthermore, gut microbiota have implications on host physiology, particularly adiposity. A paper by Le Chatelier et al. (2013) showed that microbiota composition varied between lean and obese individuals. In a study on mice by Turnbaugh et al. (2006), the microbiome of obese mice exhibited an increased capacity for energy harvest and transfer of the microbiota to non-obese mice increased their mean fat body weight, suggesting that a change in gut microbiota can induce obesity.
The human pancreas has two main functions: to produce pancreatic endorphin hormones, which help regulate many aspects of our metabolism and to produce pancreatic digestive enzymes. Pancreatic production of insulin, somatostatin, gastrin, and glucagon plays an important role in maintaining sugar and salt balance in our bodies and therefore any problem in the production or regulation of these hormones will manifest itself with problems with blood sugar and fluid / salt imbalances. Type 1 and Type 2 diabetes are two diseases that can be compared and contrasted according to their causes. Type 1 diabetes is similar to type 2 diabetes in that they are genetic diseases. Recently, researchers have been attempting to locate the genes for diabetes.
Storlien, L.H., James, D. E., Burleigh, K. M., Chisholm, D. J., & Kraegen, E. W., (1986) Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats. American Journal of Physiology, 251, E576-E583. Tsutsui,H.,Kinugawa,S., Matsushima S., & Yokota T., (2011) Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus. Journal of Clinical Biochemistry and Nutrition, 48(1), 68-71. Zhang, X., Wang, C., Song, G., Gan, K., Kong, D., Nie, Q., & Ren, L., (2013) Mitofusin-2- mediated alleviation of insulin resistance in rats through reduction in lipid intermediate accumulation in skeletal muscle.
Introduction Fatty acid synthesis plays a vital role in homeostasis within the human body. The process of fatty acid synthesis regulates energy metabolism and provides fuel in times of starvation1. This process also synthesizes biomolecules that are important to life during embryonic development and lactation in mammary glands2. An overproduction of synthesized fatty acids is implicated in disease states such as obesity, liver disease, and cancer3. The fatty acid synthase (FAS) complex performs a vital role in fatty acid synthesis.