Chapter 46: Insulin Function
A 19-year-old man is brought to the emergency room unconscious and unresponsive. There are no visible signs of trauma or head injury. The attending physician orders blood work and administration of an IV bolus of glucose. The patient regains consciousness but remains unclear of how or why he passed out. History indicates the patient is not diabetic and does not take insulin shots. However, the physician suspects the patient passed out due to insulin-induced hypoglycemia. Analysis of the patient's blood for which of the following would best confirm the physician's suspicions?
Answer A: Insulin is synthesized as a preprohormone. Its signal peptide is removed in the cisternae of the endoplasmic reticulum and it is packaged into secretory vesicles in the Golgi, folded to its native structure, and locked in this conformation by the formation of 2 disulfide bonds. Specific protease activity cleaves the center third of the molecule, which dissociates as C peptide, leaving the amino terminal B peptide disulfide bonded to the carboxy terminal A peptide. The C peptide is released along with functional insulin. In a patient in an insulin-induced coma due to injected synthetic insulin there would not be any C peptide in their blood. The presence of elevated levels of plasma C peptide in an unconscious patient could indicate an insulinoma resulting in inappropriate release of insulin leading to unexpected hypoglycemia.
You are testing the effects, on insulin function, to the addition of an unknown substance to adipocytes in culture. In the presence or absence of the compound you find that insulin binds to the adipocytes with equal affinity. Insulin alone results in a 5-fold increase in the rate of glucose uptake, above the basal rate. However, following addition of your test compound the rate of glucose uptake in response to insulin is only 0.5-fold above the basal rate. Your compound is actively taken up by the adipocytes and thus is likely exerting its effects intracellularly. Which of the following substances is your test compound most likely mimicking in this cell culture system?
Answer A: The ability of ceramides to interfere with insulin receptor signaling is the result of blocking the receptors' ability to activate the downstream effector kinase, PKB/Akt. Experiments in cell culture, involving both adipocytes and skeletal muscle cells, have ...