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?
Correct Answer: Opening of the sensitive K+ channels
Description: 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
Category:
Physiology
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