Patients suffered from insulinoma have clinical feature of hypoglycemia.Insulinoma secrets insulin without control.What's the possible mechanism?
I have published a paper on this topic: "The main product of specialized tissues regulates cell life and may cause neoplastic transformation." by Morpurgo G. Med. Hypothesis 2010 May 74 (5) 847. In this paper you may find all the bibliography on this topic. Best regards, Giorgio Morpurgo
Guo,
Normal beta cells contain glucose transporter 2 (Glut-2) and Glucokinase (GK). Both of these proteins have high Km (in the range of 13 - 15mM). Insulinomas tend to have Glut-1 and hexokinase, both are low Km versions. Transport of glucose into normal beta cells followed by its phosphorylation to Glucose-6-phosphate (the first step in glucose metabolism) is therefore dependent on the concentration of glucose in physiological range, whereas in the case of Glut-1 and hexokinase in tumor cells, even at the fasting glucose levels (3.5-5.5mM), the activity of these proteins is at their maximum level. Glucose metabolism, ultimately generates signals that are used by the cell to secrete insulin. This is why the insulinoma cells are always pumping out insulin at their maximum or near maximum levels even at 2 or 3mM glucose, which results in hypoglycemia.
Insulioma tumor cells are refractory to the negative feedback machinery regardless of the decreased level of blood glucose. Insulinoma is clinically characterized by the autonomous secretion of pro-peptide of insulin including C peptide.
thank you very much for your reply. Nexe step I will test the expression of Glucokinase and hexokinase.
Your answer supports my idea that the main product of a cell (in this case insulin)determines all aspects of the cell life. The low Km of the insulinoma variants are the cause of the continuous production of insulin and of the tumoral transformation of the cell.You can find more details in the publication:The main product of specialized tissues regulates cell life and may cause neoplastic transformation in Medical Hypothesis
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