Ph.D Thesis | |
Ph.D Student | Steinberg-Shapira Shirley |
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Subject | Deciphering of the Origin and Spread of the Activity that Leads to Insulin Secretion in Islet of Langerhans |
Department | Department of Biomedical Engineering | Supervisor | PROFESSOR EMERITUS Yoram Palti |
Islets of Langerhans are groups of cells that secrete insulin, a hormone essential for glucose metabolism. The secretion rate is determined by the cells’ electrical activity.
We developed a method, which enabled us to construct maps of the islet’s activity including the distribution of its amplitude, frequencies, as well as pathways of signal propagation. We identified a well defined pacemaker, at various locations in each islet. The pacemaker’s location within the islet was found to change under two sets of conditions: A. Unfavorable conditions for the islet activity, for example low [glucose]. B. In the presence of pharmacological agents.
Activity frequencies were found to be 0.3Hz-1.5Hz, depending on glucose concentration. Evidence was found that indicated that the pacing mechanism involves opening and closure of ion channels. Moreover, experiments with Verapamil suggested that T-type voltage dependent calcium channels may be associated with the pacemaker function.
Propagation velocities were approximately 1mm/ms. They were a direct function of temperature having a Q10 of 1.4, indicating mechanism, involving mostly physical processes. This is compatible with a propagation mechanism depending on electric currents flowing from cell to cell. The amplitude maps together with the influence of physiological ([glucose]) and pharmacological (TBA, Glyboride) agents support a propagation mechanism based on action potentials “jumping” from cell to cell through gap junctions.