A better understanding of the islets of Langerhans could lead to a new area of treating diabetes, according to Barak Blum, PhD, Assistant Professor of Cell and Regenerative Biology at the University of Wisconsin-Madison.

Dr. Blum will discuss his lab’s ongoing research into islet architecture during the afternoon symposium Orchestrating the Islet—Structural and Functional Interactions, which will begin at 4:00 p.m. CT Saturday, June 13.

The two-hour session will also feature a presentation on the delta cell and mechanisms underlying somatostatin release by Quan Zhang, PhD, Diabetes UK RD Lawrence Research Lecturer and University Research Fellow, Oxford University, as well as a look at pericytes and the microvasculature in islet function by Joana Almaca, PhD, from the University of Miami.

In his UW-Madison lab, Dr. Blum and his research team are working on answering three key questions:

• How does islet architecture form during development?
• How is islet architecture maintained in homeostasis and regeneration?
• How does islet architecture affect islet function?

The answers could someday lead to new treatments since the loss of islet organization and its specific cell-type ratios plays a key role in diabetes development.

“We may be able to inform synthesized islets to have the right architecture or manipulate islet tissue dynamics in ways that will help islets expand and keep the architecture in type 2 diabetes, for example, where islets need to expand and scale,” Dr. Blum said.

Researchers in Dr. Blum’s lab are looking into the question of islet development, focusing on Roundabout (Robo) receptors, axon-guidance proteins that control endocrine cell-type sorting in the islets of Langerhans without affecting beta-cell maturation or identity. Almost all other models of disrupted islet architecture also have defects in beta-cell maturation or identity, or pathologies related to beta-cell damage in diabetes. This leads Dr. Blum and his research team to hypothesize that the Robo βKO mouse model, where Robo1 and Robo2 genes are deleted, may be a good model to study how islet architecture affects islet function, as islet function in vivo appears to affect synchronized insulin secretion.

“The next step, and we will show some very preliminary data at the session, is that we think we’ve found some clues as to how the Roundabout receptors and their ligand, Slit, guide islet development,” Dr. Blum said. “We’ve also begun looking at the role of Robo and Slit in islet regeneration and maintenance in adults, which we think is important because the islets need to expand and shrink to accommodate life events, and Robo receptors are probably involved in that.”

Dr. Zhang will discuss the work his group has done on the molecular and cellular regulation of delta-cell somatostatin secretion. Somatostatin secretion involves a calcium (Ca²⁺)-induced Ca²⁺ release (CICR) pathway, which is regulated by glucose via modulating delta-cell intracellular cAMP. Dr. Zhang will also discuss ‘intercellular’ regulation of the delta cells: a tight coupling between single beta and delta cells that was observed by combining electrophysiology and high-speed Ca²⁺ imaging.

“Delta cells, despite their low numbers in the islets, have strong impacts on systemic blood glucose,” Dr. Zhang said, “Although its role as a potent intra-islet paracrine regulator has long been recognized, the mechanisms underlying the delta-cell somatostatin regulation remain elusive. Better understanding of the delta cells will provide avenues for developing novel pharmacological interventions for optimized glycemic control.”