Thursday, November 15, 2012

LIPOTOXICITY AND GLUCOTOXICITY


LIPOTOXICITY

The main function of adipose tissue is to store energy in the form of TAG in postprandial state and release them as glycerol and FFA in fasting or starved state. Accumulation of lipids and their harmful effect is called lipotoxicity which can cause hepatic steatosis, lipid induced cardiomyopathy, insulin resistance and type 2 diabetes mellitus. Increase in NEFA cause underutilization of glucose and insulin resistance by 3 mechanisms.

(1) Via randle cycle glucose cannot enter glycolytic pathway due to accumulation of citrate that inhibit PFK.

(2) DAG which is formed during fatty acid metabolism activates PKC which phosphorylates insulin receptor and insulin receptor substrate (IRS)-1 inactivating them

(3) it also activates NFkB which damages vessels. In liver NEFA inhibit the suppression of glycogenolysis by insulin. Many patients with obesity and increased plasma NEFA do not develop diabetes because NEFAs are potent stimulators of insulin secretion in normal individuals an effect that might mitigate the tendency for NEFAs to induce insulin resistance.

GLUCOTOXICITY:

Highly elevated glucose can induce insulin resistance characterized by impaired insulin secretion in response to glucose. 
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