2953-LB: Transdifferentiation of Delta to Beta Cells during Normal and Hyperglycemic Pregnancy

Introduction and Objective: Pancreatic β-cell number increases during pregnancy to compensate for insulin resistance. While this involves β-cell proliferation a transdifferentiation from other islet cell types, such as somatostatin (Sst)-secreting δ-cells, may also occur. It is unclear whether δ-cell mass (DCM) is also increased during pregnancy, the extent to which transdifferentiation contributes to increased β-cell mass (BCM), or how these change in a hyperglycemic pregnancy.Methods: We used a transgenic mouse model to trace δ-cell lineage fate using a yellow fluorescent protein (YFP) tag. Pancreata were collected from non-pregnant (NP) females and from pregnant mice between gestational days (GD) 9 and 18, and processed for immunofluorescence histochemistry to detect Ins, YFP, and Sst. Mice (6-8-weeks age) received either no injection, buffer, or streptozotocin (STZ) to induce β-cell loss. Two weeks post-injection, mice were mated and pancreas removed for histology.Results: BCM and DCM significantly increased by GD18 compared to NP (GD18, BCM 0.22±0.05 mg (Mean±sem), DCM 0.05±0.01 mg; NP, BCM 0.060±0.003, DCM 0.020±0.003). A 5-6-fold increase in both bi-hormonal (BH; Ins⁺ YFP⁺ Sst⁺) and transdifferentiated (TD; Ins+YFP+Sst-) cells was seen by GD18 in normal pregnancy, although TD cells were less abundant (GD18, BH 6.32±.0.76% vs. all Ins+, TD 2.17±0.24%; NP, BH 1.37±0.14%, TD 0.38 ±0.14%). STZ-treated mice had an initial 40% reduction in BCM and were glucose intolerant during pregnancy. The adaptive increase in BCM, but not DCM, was impaired in hyperglycemic pregnant mice, although the relative presence of BH and TD cells was increased, relative to buffer-treated controls.Conclusion: Both BCM and DCM increased during pregnancy and increased δ- to β-cell transdifferentiation occurred with a bihormonal intermediate phenotype. During hyperglycemic pregnancy the increase in BCM was impaired, although the relative contribution of TD to generate new β-cells was greater.

B. Thirunavukarasu: None.



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