Serum from pregnant donors induces human beta cell proliferation

ABSTRACT

Pancreatic beta cells are among the slowest replicating cells in the human body and have not been observed to increase in number except during the fetal and neonatal period, in cases of obesity, during puberty, as well as during pregnancy. Pregnancy is associated with increased beta cell mass to meet heightened insulin demands. This phenomenon raises the intriguing possibility that factors present in the serum of pregnant individuals may stimulate beta cell proliferation and offer insights into expansion of the beta cell mass for treatment and prevention of diabetes. The primary objective of this study was to test the hypothesis that serum from pregnant donors contains bioactive factors capable of inducing human beta cell proliferation. An immortalized human beta cell line with protracted replication (EndoC-βH1) was cultured in media supplemented with serum from pregnant and non-pregnant female and male donors and assessed for differences in proliferation. This experiment was followed by assessment of proliferation of primary human beta cells. Sera from five out of six pregnant donors induced a significant increase in the proliferation rate of EndoC-βH1 cells. Pooled serum from the cohort of pregnant donors also increased the rate of proliferation in primary human beta cells. This study demonstrates that serum from pregnant donors stimulates human beta cell proliferation. These findings suggest the existence of pregnancy-associated factors that can offer novel avenues for beta cell regeneration and diabetes prevention strategies. Further research is warranted to elucidate the specific factors responsible for this effect.

GRAPHICAL ABSTRACT

KEYWORDS:

• Beta cell
• diabetes
• EdU
• EndoC-βH1, proliferation
• human
• insulin
• islet
• pregnancy
• primary
• serum

Acknowledgments

We thank the serum donors for agreeing to participate in the study. Thank you to Jacquelyn Walejko, Ph.D., Graduate Research Assistant, University of Florida, for assisting with serum donor information. Present affiliation: Domus Diagnostics, Inc., Durham, NC.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

K.S. and C.R. recruited patients, collected sera, and performed beta cell experiments. A.P. and M.B. performed experiments. D.H. and J.C. setup and cared for beta cell cultures. C.E.M., C.W., M.A., and R.E. provided critical equipment, reagents, expertise, and support. K.S., M.A., R.E. and E.P. conceived the study. K.S. and E.P. analyzed data and wrote the manuscript. All authors contributed to the discussion and reviewed/edited the manuscript. E.P. is the guarantor of this work and, hence, had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Data and resource availability

All data points generated or analyzed during this study are included in the published article (and its online supplementary files). Human serum donor information is listed in Table 1 and islet donor information is listed in Table 2. Further information on the primary human islets analyzed are available in the IIDP repository using the provided RRID numbers: https://iidp.coh.org/[RRID: SAMN13028024; SAMN32641505, SAMN38788294]. No other applicable resources were generated.

Ethical approvals

This protocol was approved by the Institutional Review Board (IRB) and the University of Florida (UF IRB20150007, IRB201902512). Primary human pancreatic islets from deceased nondiabetic donors were obtained from the Integrated Islet Distribution Program (IIDP) at City of Hope. Human pancreatic islets used were approved as non-human by the University of Florida IRB (IRB no. 201701113, 201702860).

Preprint

The submitted version of this manuscript has been posted on the BioRxiv preprint server under DOI 10.1101/2023.04.17.537214.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19382014.2024.2334044.

Additional information

Funding

Research reported in this publication was supported by NIH grant # R01DK132387, JDRF grant # 2-SRA-2023-1313-S-B, and the University of Florida Clinical and Translational Science Institute, which is supported in part by the NIH National Center for Advancing Translational Sciences under award number # UL1TR001427. Human pancreatic islets were provided by the NIDDK-funded Integrated Islet Distribution Program (IIDP) at City of Hope, NIH grant # 2UC4DK098085 and the JDRF-funded IIDP Islet Award Initiative. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.