Pancreatic islets were isolated from a healthy, non-diabetic donor to perform an experiment to look at insulin secretion inhibition. Compounds would be added to separate wells containing the islets bathed in a high glucose solution for one hour. After one hour, the supernatant would be collected, and the insulin content would be measured with an enzyme-linked immunosorbent assay (ELISA). Which of the following compounds would result in the least insulin secretion when added to the islets?
1.Dobutamine
2.Isoproterenol
3.Tolbutamide
4.Cloidine
5.Glyburide
Explanation
Alpha agonists decrease insulin secretion. Therefore, when clonidine, an alpha-2 agonist, is added to the solution, it would decrease the amount of insulin secretion when stimulated with glucose.
Insulin is a 51 amino acid di-peptide (A and B chain) linked by disulfide bonds. It is synthesized in the beta cells of the pancreas as proinsulin (insulin + C-peptide) and is cleaved in the secretory vesicle. When insulin is released, both the c-peptide and insulin are released. Endogenous insulin should contain both insulin and C-peptide; if hyperinsulinemia occurs and similar concentrations of C-peptide are not found, then the insulin is of exogenous origin. Hyperglycemia, growth hormone, cortisol, and beta agonists increase insulin release while hypoglycemia, somatostatin, and alpha agonists decrease insulin release. As in the question, clonidine is an alpha-2 agonist that decreases central adrenergic outflow and is primarily used to treat hypertension but does not decrease blood flow to the kidney.
Illustration A demonstrates the synthesis of insulin from pre-proinsulin in the ER to proinsulin in the Golgi apparatus to insulin in the secretory vesicle. Illustration B depicts the pathway for insulin release.