טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentSteinberg-Shapira Shirley
SubjectDeciphering of the Origin and Spread of the Activity that
Leads to Insulin Secretion in Islet of Langerhans
DepartmentDepartment of Biomedical Engineering
Supervisor Professor Emeritus Yoram Palti


Abstract

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.