Postnatal Exocrine Pancreas Growth by Cellular Hypertrophy Correlates with a Shorter Lifespan in Mammals

Shira Anzi, Miri Stolovich-Rain, Agnes Klochendler, Ori Fridlich, Aharon Helman, Avital Paz-Sonnenfeld, Nili Avni-Magen, Elizabeth Kaufman, Miriam B. Ginzberg, Daniel Snider, Saikat Ray, Michael Brecht, Melissa M. Holmes, Karen Meir, Aaron Avivi, Imad Shams, Asaf Berkowitz, A. M.James Shapiro, Benjamin Glaser, Shmuel Ben-SassonRan Kafri, Yuval Dor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Developmental processes in different mammals are thought to share fundamental cellular mechanisms. We report a dramatic increase in cell size during postnatal pancreas development in rodents, accounting for much of the increase in organ size after birth. Hypertrophy of pancreatic acinar cells involves both higher ploidy and increased biosynthesis per genome copy; is maximal adjacent to islets, suggesting endocrine to exocrine communication; and is partly driven by weaning-related processes. In contrast to the situation in rodents, pancreas cell size in humans remains stable postnatally, indicating organ growth by pure hyperplasia. Pancreatic acinar cell volume varies 9-fold among 24 mammalian species analyzed, and shows a striking inverse correlation with organismal lifespan. We hypothesize that cellular hypertrophy is a strategy for rapid postnatal tissue growth, entailing life-long detrimental effects. Anzi et al. show that postnatal pancreas growth in mice relies to a large extent on cell growth, while human pancreas growth involves only increased cell numbers. Comparative analysis of 24 mammalian species revealed a striking negative correlation between pancreatic acinar cell size and organismal lifespan.

Original languageAmerican English
Pages (from-to)726-737.e3
JournalDevelopmental Cell
Volume45
Issue number6
DOIs
StatePublished - 18 Jun 2018

Bibliographical note

Funding Information:
Funded by grants from the Israeli Science Foundation (627/14), The Juvenile Diabetes Research Foundation (JDRF), The Helmsley Charitable Trust , the DON Foundation , and the I-CORE Program of The Israel Science Foundation (ISF) #41.11. This research was performed using grants from the NIDDK-supported Human Islet Research Network (RRID: SCR_014393 ; https://hirnetwork.org ; UC4 DK104216-01 to Y.D.), and with the support of the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project sponsored by JDRF. Organ procurement organizations partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/for-partners/npod-partners/ . Supported by grants from USAID's American Schools and Hospitals Abroad Program for the upgrading of the Hebrew University Medical School flow cytometry laboratory, sequencing core, and confocal imaging unit. We thank Chamutal Gur for help with salivary gland harvest. We are grateful to Ms. Norma Kiddes-Basir for excellent histology services. We thank Markus Grompe and Craig Dorrell for the gift of acinar cell surface antibodies, and Eli Pikarsky, Manami Hara, David Harlan, David Blodget, Patrik Rorsman, and Maureen Gannon for discussions and sharing unpublished information.

Funding Information:
Funded by grants from the Israeli Science Foundation (627/14), The Juvenile Diabetes Research Foundation (JDRF), The Helmsley Charitable Trust, the DON Foundation, and the I-CORE Program of The Israel Science Foundation (ISF) #41.11. This research was performed using grants from the NIDDK-supported Human Islet Research Network (RRID:SCR_014393; https://hirnetwork.org; UC4 DK104216-01 to Y.D.), and with the support of the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project sponsored by JDRF. Organ procurement organizations partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/for-partners/npod-partners/. Supported by grants from USAID's American Schools and Hospitals Abroad Program for the upgrading of the Hebrew University Medical School flow cytometry laboratory, sequencing core, and confocal imaging unit. We thank Chamutal Gur for help with salivary gland harvest. We are grateful to Ms. Norma Kiddes-Basir for excellent histology services. We thank Markus Grompe and Craig Dorrell for the gift of acinar cell surface antibodies, and Eli Pikarsky, Manami Hara, David Harlan, David Blodget, Patrik Rorsman, and Maureen Gannon for discussions and sharing unpublished information.

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • cell size
  • exocrine pancreas
  • hyperplasia
  • hypertrophy
  • islets
  • lifespan
  • nucleolus
  • postnatal development
  • salivary glands
  • weaning

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