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What is A 30 year old male presents with recurrent attacks of sweating and dizziness. Fuher workup reveals low blood glucose levels with inappropriatlely elevated insulin and C-peptide levels. Imaging shows a lesion in the pancreas. He is diagnosed with insulinoma and given diazoxide. Which of the following is the mechanism of action of this drug? and explain in detail?
Diazoxide acts by opening ATP sensitive K+ channels and causing a decrease in insulin secretion. Glucose enters beta cells of the pancreas GLUT-2 receptors. Once inside, it is phosphorylated by glucokinase (rate-limiting step) to glucose-6-phosphate which is oxidized to form adenosine triphosphate(ATP). This leads to opening volatge-gated calcium channels and Ca+2 influx. This stimulates fusion of the insulin-containing vesicles with the cell membrane and secretion of insulin into the extracellular fluid by exocytosis. Diazoxide keeps the ATP sensitive K+ channels open, and prevents depolarisation and subsequent insulin release. Sulfonylureas cause closure of the ATP sensitive K+ channels, leading to an insulin secretion. REF: Guyton and Hall 13th edition PGno: 989