Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro
<p>Pseudopregnancy promotes beta cell mass expansion in parous mice. (<b>A</b>) Representative pancreata stained with insulin (magenta) and DAPI (blue) from each treatment group, 5× tile images stitched using ImageJ. (<b>B</b>) Quantification of beta cell mass (insulin/DAPI ratio); <span class="html-italic">n</span> = 3–6, * <span class="html-italic">p</span> = 0.02 using Kruskal-Wallis non-parametric test.</p> "> Figure 2
<p>Pregnancy hormones induce beta cell proliferation but not hypertrophy in mice. (<b>A</b>) Immunohistochemical staining for the replication marker Ki67 (red) and insulin (green) at 20× magnification. (<b>B</b>) Statistical analysis of Ki67+ beta cells; <span class="html-italic">n</span> = 3–5, ** <span class="html-italic">p</span> = 0.01 using Kruskal–Wallis non-parametric test. (<b>C</b>) No change (ns) in beta cell area was found in any group; ANOVA <span class="html-italic">p</span> = 0.09, <span class="html-italic">n</span> = 3. (<b>D</b>) Islets stained with E-cadherin; white blocked cells represent beta cell area quantification method (see methods section).</p> "> Figure 3
<p>E + PL induce STAT5 signaling in the pseudopregnancy model. (<b>A</b>) Immunohistochemical staining for PRLR in nulliparous (top) and parous (bottom) mouse islets. (<b>B</b>) STAT5 expression in nulliparous (top) and parous (bottom) mouse islets. Open arrowheads show minimal accumulation, while white arrows show maximal accumulation.</p> "> Figure 4
<p>In-Vitro pseudopregnancy model promotes beta cell replication in human islets and INS1E cells. (<b>A</b>) Representative immunocytochemistry showing EdU incorporation (red) in beta cells (green) from the INS1E cell line (top row), and female human islets (bottom row) after treatment with E and PL. (<b>B</b>) Quantification of the proliferation of INS1E cells under the pseudopregnancy assay. INS1E control group and E + PL group (** <span class="html-italic">p</span> < 0.01) as well as between PL and E + PL (<span class="html-italic">p</span> < 0.05) showed significant differences, <span class="html-italic">n</span> = 3. (<b>C</b>) EdU incorporation in female human islets treated with E and PL were statistically different from untreated control cells (* <span class="html-italic">p</span> < 0.05 by ANOVA); <span class="html-italic">n</span> = 3.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Mice
2.2. In Vivo Pseudopregnancy Model: Pellet Implantation and PL Injections
2.3. Histology
2.4. Histology Quantification
2.5. Cell Culture
In Vitro Pseudopregnancy Proliferation Assay
2.6. Statistical Analysis
3. Results
3.1. Pseudopregnancy Promotes Beta Cell Proliferation in Multiparous Mice In-Vivo
3.2. Pseudopregnancy Induces Beta Cell Replication In Vitro
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Nulliparous | Parous |
---|---|
Nulliparous + Estrogen (D0-D11) | Parous + Estrogen (D0-D11) |
Nulliparous + Placental Lactogen (D7-D11) | Parous + Placental Lactogen (D7-D11) |
Nulliparous + Estrogen (D0-D11) + Placental lactogen (D-D11) | Parous + Estrogen (D0-D11) + Placental lactogen (D7-D11) |
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Millette, K.; Rodriguez, K.; Sheng, X.; Finley, S.D.; Georgia, S. Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro. Biomolecules 2022, 12, 215. https://doi.org/10.3390/biom12020215
Millette K, Rodriguez K, Sheng X, Finley SD, Georgia S. Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro. Biomolecules. 2022; 12(2):215. https://doi.org/10.3390/biom12020215
Chicago/Turabian StyleMillette, Katelyn, Keith Rodriguez, Xia Sheng, Stacey D. Finley, and Senta Georgia. 2022. "Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro" Biomolecules 12, no. 2: 215. https://doi.org/10.3390/biom12020215