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Published: 2019-08-16 10:58 | Updated: 2019-08-16 11:54

Novel findings explain indirect regulation of glucose homeostasis

Per-Olof Berggren, PhD, Professor, Department of Molecular Medicine and Surgery, Karolinska Institutet.

The hormone secreting part of the pancreas, the islets of Langerhans, has a unique cyto-architecture that allows functional interrelationships between the different cell types. Somatostatin is secreted by the delta cell and is an effective inhibitor of the insulin secreting beta cell and the glucagon secreting alpha cell. According to a novel study from Karolinska Instiutet, published in the journal Nature Communications, the delta cell can thereby indirectly affect glucose homeostasis

“Our results provide important insight into the activity of the delta cell in health and pre-diabetes and a possible mechanism for how somatostatin so effectively can exert its potent suppressive effects within the islet of Langerhans”, comments senior study-author Professor Per-Olof Berggren of the Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet in Sweden, who is also a visiting professor at Lee Kong Chian School of Medicine, Singapore. 

Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, Per-Olof Berggren and his colleagues show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach large numbers of beta cells within the islet. 

Efficient regulation

This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. 

 “It has since long been a mystery how delta cells so effectively can regulate the function of alpha- and beta cells only constituting a minority among the hormone secreting cells”, says Per-Olof Berggren. “These are fundamental data explaining an important structure/function relationship between delta cells and other hormone secreting cells and provides the basis for how delta cells, despite being in minority, can act as efficient modulators of glucose homeostasis.”

This work was supported by, amongst others, the Lee Kong Chian School of Medicine NTU in Singapore, the Lee Foundation, the Swedish Research Council, the Family Erling-Persson Foundation, the Novo Nordisk Foundation, the Stichting af Jochnick Foundation, the Swedish Diabetes Association, the Skandia Insurance Company Ltd., Diabetes Research and Wellness Foundation, Berth von Kantzow’s Foundation, the Strategic Research Program in Diabetes at Karolinska Institutet, the European Research Council, and the Knut and Alice Wallenberg Foundation. Professor Berggren is the founder and CEO of Biocrine, a biotech company focusing on the development of new diabetes drugs. 

Publication

“Structural basis for delta cell paracrine regulation in pancreatic islets”
Rafael Arrojo e Drigo, Stefan Jacob, Concha F. García-Prieto, Xiaofeng Zheng, Masahiro Fukuda, Hoa Tran Thi Nhu, Olga Stelmashenko, Flavia Letícia Martins Peçanha,Rayner Rodriguez-Diaz, Eric Bushong, Thomas Deerinck, Sebastien Phan, Yusuf Ali, Ingo Leibiger, Minni Chua, Thomas Boudier, Sang-Ho Song, Martin Graf, George J. Augustine, Mark H. Ellisman, Per-Olof Berggren.
Nature Communications, online 16 August 2019.