Question

provide some details regarding one aspect of how altering AMP kinase activity provides a link between hyperglycemia and diabetic nephropathy. One healthy paragraph with

details should be sufficient.

Answer 1

In type 2 diabetes , there is down regulation of amp dependent protein kinase ,, thus high fatty acid may cause accumulation of DAG( diacyglycerol) and PKC activation which impairs insulin signalling by phosphorylating insulin receptor substrate in skeletal muscle , adipocytes , and liver . This free fatty acid also produces inflammation.  

PHYSIOLOGICAL ROLE OF AMP DEPENDENT PROTEIN KINASE :

• It inhibits lipid and cholesterol synthesis
• It stimulates glucose uptake by fusion of glut4 receptors with plama membrane
• Ampk increases m-rna expression of glut4 and hexokinase and increases glucose uptake
• It also increases Expression of glut 1
• It stimulates glycolysis
• At high level it causes glycogen sunthesis

Role of ampk in diabetic nephropathy :

• due to decreased ampk activity,, hyperglycemia results.
• Which induces renal damage directly
• Increased activation of protein kinase c and diacylglycerol which causes abnormal stimulation of renal cells which secrete TGF 1 beta , which in turn causes deposition of extracellular matrix and thickening of glomerular basement membrane . Thus indicating diabetic nephropathy .

ROLE OF METFORMIN IN ENHANCING AMPK ACTIVITY:

• Metformin enchances ampk activity by increasing glycolysis and peripheral glucose uptake and inhibiting gluconeogenesis in liver .
• It is the 1st choice of drug in type 2 diabetes
• It donot produce hypoglycemia as side effects becoz it donot stimulate insulin secretion
• It has a neutral effect in weight
• Only side effects produced are lactic acidosis , vitamin b12 deficiency and bloating which should be considered.