Achieving Productive Beta-cell Proliferation

• Applicant: Professor Nikolay Ninov, Ph.D.
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421532820

• Final Report Year: 2024

Final Report Abstract

The collaboration has led to the identification a conserved process of aberrant survival of beta-cells during proliferation. This process is of important clinical relevance since it implies that triggering beta-cell proliferation can lead to failed regeneration. Here, we have been able to peer into the molecular mechanisms that lead to the cell death and we have already uncovered pathways that can be manipulated in the clinic to facilitate the regeneration of beta-cells as a future therapy.

Publications

• Leader β-cells coordinate Ca2+ dynamics across pancreatic islets in vivo. Nature Metabolism, 1(6), 615-629.
  Salem, Victoria; Silva, Luis Delgadillo; Suba, Kinga; Georgiadou, Eleni; Neda, Mousavy Gharavy S.; Akhtar, Nadeem; Martin-Alonso, Aldara; Gaboriau, David C. A.; Rothery, Stephen M.; Stylianides, Theodoros; Carrat, Gaelle; Pullen, Timothy J.; Singh, Sumeet Pal; Hodson, David J.; Leclerc, Isabelle; Shapiro, A. M. James; Marchetti, Piero; Briant, Linford J. B.; Distaso, Walter ... & Rutter, Guy A.
  
• A single-cell atlas of de novo β-cell regeneration reveals the contribution of hybrid β/δ-cells to diabetes recovery in zebrafish.
  Singh, Sumeet Pal; Chawla, Prateek; Hnatiuk, Alisa; Kamel, Margrit; Silva, Luis Delgadillo; Spanjard, Bastiaan; Eski, Sema Elif; Janjuha, Sharan; Olivares, Pedro; Kayisoglu, Oezge; Rost, Fabian; Bläsche, Juliane; Kränkel, Annekathrin; Petzold, Andreas; Kurth, Thomas; Reinhardt, Susanne; Junker, Jan Philipp & Ninov, Nikolay
  
• Biphasic dynamics of beta cell mass in a mouse model of congenital hyperinsulinism: implications for type 2 diabetes. Diabetologia, 64(5), 1133-1143.
  Tornovsky-Babeay, Sharona; Weinberg-Corem, Noa; Ben-Haroush, Schyr Rachel; Avrahami, Dana; Lavi, Judith; Feleke, Eseye; Kaestner, Klaus H.; Dor, Yuval & Glaser, Benjamin
  
• Glycemic control releases regenerative potential of pancreatic beta cells blocked by severe hyperglycemia. Cell Reports, 41(9), 111719.
  Furth-Lavi, Judith; Hija, Ayat; Tornovsky-Babeay, Sharona; Mazouz, Adi; Dahan, Tehila; Stolovich-Rain, Miri; Klochendler, Agnes; Dor, Yuval; Avrahami, Dana & Glaser, Benjamin
  
• Wnt4 is heterogeneously activated in maturing β-cells to control calcium signaling, metabolism and function. Nature Communications, 13(1).
  Katsumoto, Keiichi; Yennek, Siham; Chen, Chunguang; Silva, Luis Fernando Delgadillo; Traikov, Sofia; Sever, Dror; Azad, Ajuna; Shan, Jingdong; Vainio, Seppo; Ninov, Nikolay; Speier, Stephan & Grapin-Botton, Anne
  
• Extensive elimination of acinar cells during normal postnatal pancreas growth. Cell Reports, 42(12), 113457.
  Stolovich-Rain, Miri; Fridlich, Ori; Azulai, Shira; Klochendler, Agnes; Anzi, Shira; Magenheim, Judith; Stein, Ilan; Mushasha, Fatima; Glaser, Benjamin; Pikarsky, Eli; Ben-Zvi, Danny & Dor, Yuval