The insulin-producing cell's stress hormone receptor helps prevent high blood sugar when hormone rhythms are disturbed in mice

Glucocorticoid rhythm flattening in mice produced sustained hyperinsulinaemia with maintained euglycaemia.

• Flattened glucocorticoid rhythms resulted in increased insulin secretion from beta cells at lower glucose levels.
• Beta cell-specific deletion of the glucocorticoid receptor significantly reduced the hyperinsulinaemic response, highlighting its role in insulin regulation.
• Despite elevated insulin levels, the mice did not experience hypoglycaemia, suggesting concurrent insulin resistance.
• Reduced insulin clearance, indicated by a lower plasma C-peptide:insulin ratio and decreased hepatic insulin-degrading enzyme abundance, contributed to elevated circulating insulin.
• These findings suggest that glucocorticoid receptor signalling in beta cells is crucial for glucose homeostasis when glucocorticoid rhythmicity is disrupted.

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