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University of Oxford researchers have uncovered surprising new insights into how the pancreas adapts during pregnancy to meet the body’s increased demand for insulin. Their findings, published in Nature Communications, challenge long-standing assumptions based on animal studies and highlight key differences between human and mouse biology.

Pancreas cells. Islets of Langerhans  (small clusters of insulin-producing β cells and glucagon-producing α cells

Pregnancy requires the maternal body to undergo complex changes in order to support the growing fetus. One of the most critical adjustments takes place in the pancreas, where the islets of Langerhans  (small clusters of insulin-producing β cells and glucagon-producing α cells) adapt to maintain glucose balance. Failure of this system underpins gestational diabetes mellitus (GDM), the most common pregnancy-related metabolic disorder.

Key discoveries

Using rare, high-quality pancreatic tissue from pregnant organ donors, Oxford scientists applied advanced proteomic profiling and immunohistochemistry to study how human islets remodel during pregnancy.

  • Islet size expands: The area occupied by islets increased nearly two-fold, with α cells growing by over four-fold and β cells by almost two-fold. This expansion was driven by an increase in cell number, not cell size.

  • Distinct from mouse models: Unlike in mice, human β cells showed no evidence of proliferation during pregnancy. Instead, the increase appears linked to altered intra-islet signalling.

  • Receptor shifts: Prolactin receptors (PRLR) and serotonin 2B receptors (5-HT2B) were more abundant in α cells, not β cells – a striking contrast with mouse findings.

  • GLP-1 boost: Levels of the hormone glucagon-like peptide-1 (GLP-1) rose nearly three-fold in α cells. GLP-1 is known to enhance insulin release from β cells, suggesting that α cells may play an unexpectedly central role in supporting insulin output during pregnancy.

Read the full story on the Nuffield Dept.of Women's & Reproductive Health website.