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Signaling Pathway Mediates Steroid-Induced Diabetes

Blocking pathway can restore pancreatic β-cell function, study finds

THURSDAY, May 28 (HealthDay News) -- Steroid-induced pancreatic β-cell dysfunction and diabetes mellitus are mediated through a cellular signaling pathway that, when blocked, can restore β-cell function, according to a study published online May 14 in Endocrinology.

Building on evidence from previous studies, Xiongfei Zhang and colleagues from Nanjing Medical University in China examined the role of Forkhead Box O1 (FoxO1), a transcription factor that regulates insulin and insulin-like growth factor-1 signaling pathways, in dexamethasone-induced pancreatic β-cell dysfunction.

The researchers found that dexamethasone increased the level of active FoxO1 in both pancreatic β-cells and in isolated rat islets. The activated protein inhibited the expression of the pancreatic duodenal homeobox-1 (Pdx-1) gene, a key regulator of β-cell development, differentiation, and function. Blocking FoxO1 expression restored Pdx-1 expression and blocked dexamethasone-induced dysfunction of glucose-stimulated insulin secretion from rat islets.

"Together, the results of the present study demonstrate that FoxO1 is integrally involved in dexamethasone-induced inhibition of Pdx-1 and glucose-stimulated insulin secretion dysfunction in pancreatic islet β-cells," Zhang and colleagues conclude. "Inhibition of FoxO1 can effectively protect β-cells against dexamethasone-induced dysfunction."

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