I study physiology of hormone secretion by pancreatic islets of Langerhans. My work takes advantage of techniques for real-time monitoring of metabolism or signalling within the islet cells, such as imaging by various modes of fluorescence microscopy and patch-clamp electrophysiology. To account for the heterogeneity of the cells within the islet and the heterogeneity of the islets themselves, high content routines have been implemented into the real-time imaging technology. Enhancement of energy metabolism of pancreatic β-cell by extracellular stimulus (glucose) is a key prerequisite to insulin secretion and at the same time a major source of conundrums in the diabetes research.
In the distant past I studied the interaction of β-cell metabolic signalling with the KATP channel, a key step that leads to plasma membrane depolarisation. The logical progression for this work were studies on the regulation of β-cell metabolism by the events downstream of the plasma membrane depolarisation, such as Ca2+ influx. My current research aims to explore how glucose regulates the metabolism over longer periods of time - hours, days; and identify the factors affecting the onset or offset of the metabolic activation. To resolve this problem, I image the islet cell metabolism (ATP, mitochondrial membrane potential, NADH) alone or in parallel with imaging of hormone secretion. Another key topic of my interest is the cross-talk between different cell types within pancreatic islet, which is mostly implemented by the soluble peptides (hormones) they secrete. The peptides then induce changes in intracellular molecules such as cAMP and DAG, thereby influencing the secretory abilities of the target cells. I perform real-time imaging of islet populations to resolve the mechanisms of the cross talk as well as how these mechanisms are affected by chronic metabolic factors.
Imaging Calcium Dynamics in Subpopulations of Mouse Pancreatic Islet Cells.
Hamilton A. et al, (2019), J Vis Exp
Monitoring real-time hormone release kinetics via high-content 3-D imaging of compensatory endocytosis.
Tarasov AI. et al, (2018), Lab Chip, 18, 2838 - 2848
Adrenaline Stimulates Glucagon Secretion by Tpc2-Dependent Ca2+ Mobilization From Acidic Stores in Pancreatic α-Cells.
Hamilton A. et al, (2018), Diabetes, 67, 1128 - 1139