Mechanistic role of citrus flavonoids and their glycoconjugates in the management of Type 2 diabetes

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Mechanistic role of citrus flavonoids and their glycoconjugates in the management of Type 2 diabetes

Show simple item record Dhanya., R Dr. P. Jayamurthy 2017-07-05T05:43:53Z 2017-07-05T05:43:53Z 2016-02-22
dc.description.abstract The incidence of diabetes is rapidly increasing and by 2030 an expected 592 million individuals are projected to be affected (WHO report). Hyperglycaemic condition is recognized as the causal link between diabetes and its complications. The chronic hyperglycemia resulting from diabetes brings about a rise in oxidative stress due to overproduction of reactive oxygen species (ROS) as a result of glucose auto oxidation and protein glycosylation. Generation of ROS leads to oxidative damage of the structural components (such as lipids, DNA and proteins) of cells and potentiate diabetes related complications. Oxidative insult in cells is also created by the impairment in functioning of endogenous antioxidant enzymes because of their non enzymatic glycosylation and oxidation. The prolonged exposure of oxidative stress may cause insulin resistance by triggering an alteration in cellular redox balance. Several lines of evidence suggest that oxidative stress occurs in diabetes and could have a role in the development of insulin resistance. The cause and cellular mechanism responsible for this abnormality is not fully understand despite of intense investigative efforts. However it is unknown whether it is the cause or consequence of diabetes. Despite strong experimental evidence indicating that oxidative stress may determine the onset and progression of late-diabetic complications, controversy exists between the cause and associative relationship between oxidative stress and diabetes mellitus. Disruption of glucose homeostasis is a characteristic feature of Non-insulin dependent diabetes mellitus (NIDDM) and is associated with some complications including cardiovascular disease and renal failure. Glucose transport, the rate limiting step in glucose metabolism, can be activated in peripheral tissues by two distinct pathways. One stimulated by insulin through IRS-1/PI3K, Preface Page 2 the other by muscle contraction/exercise through the activation of AMPK. Both pathways also increase the phosphorylation and activity of MAPK family components of which p38 MAPK participates in the full activation of GLUT4.Insulin exerts its biological effect upon binding with the insulin receptor (IR) thereby activating the downstream signaling that lead to enhanced glucose uptake. In skeletal muscle, it potentiates glucose transport through PI3K mediated or non-PI3K mediated pathways. Alterations or defects in its signal transduction pathway was found in diabetic patients associated with decreased levels of IRb, IRS-1, and PI3K. In the insulin signaling, PI3K is a key molecule and inhibition of PI3K completely abolish insulin stimulated uptake. Akt or Pkb is an important downstream target of insulin stimulated glucose transport and metabolism.Impairment in fuel metabolism occurs in obesity, and this impairment is a leading pathogenic factor in type 2 diabetes. The insulin resistance associated with type 2 diabetes is most profound at the level of skeletal muscle as this is the primary site of glucose and fatty acid utilization. Therefore, an understanding of how to activate AMPK in skeletal muscle would offer significant pharmacologic benefits in the treatment of type 2 diabetes. Metformin and the thiazolidinedione drugs exert the effects via activation of AMPK. Activation of AMPK occurs in response to exercise, an activity known to have significant benefit for type 2 diabetics. AMPK serves as sensor of energy status whose activity is triggered in response to changes in nutritional status in order to modulate tissue-specific metabolic pathways en_US
dc.language.iso en en_US
dc.publisher Cochin University of Science and Technology en_US
dc.subject Hypoglycemic en_US
dc.subject Nucleotide sequences en_US
dc.subject Diabetes en_US
dc.subject Type I diabetes mellitus en_US
dc.subject Pathways involved in glucose transport en_US
dc.title Mechanistic role of citrus flavonoids and their glycoconjugates in the management of Type 2 diabetes en_US
dc.type Thesis en_US

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