Ph.D Thesis

Ph.D StudentHaim-Langford Daphne
SubjectModulation of the Electric Activity of Islets of
Langerhans by Anesthetic Agents
DepartmentDepartment of Biotechnology
Supervisor PROFESSOR EMERITUS Yoram Palti


Background: Most anesthetics were found to alter glucose metabolism. However, their mode of interfering with glucose metabolism is only partially understood. The objective of this study was to test the assumption that surgical hyperglycemia results from a direct effect of anesthetics on the electric activity of islet of Langerhans. Methods: 1.The effect of a variety of anesthetic agents on the electric signals generated by intact isolated gerbil islets of Langerhans were measured by an electrophysiological system named Electro-islet-gram (EIG). 2. The effect of thiobarbiturates on the electric signals of a b-cell monolayer and on their synchronization were studied by means of multi-electrode array (MEA) 3. The effect of thiopental on gap-junction permeability was examined by microinjection experiments. Results: The major findings of the EIG experiments are the inhibitive effect of thiopental and ketamine, on the amplitude of the EIG, and the inhibitive effect of pentobarbital and isoflurane on the frequency of the EIG. The MEA’s experiments demonstrated that thiopental reduces the amplitude of b-cell monolayer and interferes with the synchronization between adjacent cells. Finally, we found that thiopental reduces the permeability of b-cell gap-junctions. Conclusions: The present work suggests that one of the mechanisms by means of which general anesthetics contribute to hyperglycemia of surgery is by interfering in the biophysical properties of the islets of Langerhans. Thiopental in particular causes a reduction of b-cell monolayer signal amplitude, synchronization between the activity of the cells within the islet as well as coupling between them. The latter finding can explain the inhibitory effect of thiopental on glucose clearance during surgery.