Oren-gedoku-to suppresses hypothalamic adenosine 5′-monophosphate-activated protein kinase activity and olanzapine-induced hyperglycemia

Kusakabe, Yuna; Ishiwata, Yasuyoshi; Nagata, Masashi

doi:10.22038/ajp.2025.26628

Oren-gedoku-to suppresses hypothalamic adenosine 5′-monophosphate-activated protein kinase activity and olanzapine-induced hyperglycemia

Articles in Press

Document Type : Short communication

Authors

¹ Department of Pharmacokinetics and Pharmacodynamics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU)

² bDepartment of Pharmacy, Tokyo Medical and Dental University Hospital, Tokyo Medical and Dental University (TMDU)

10.22038/ajp.2025.26628

Abstract

Objective: Atypical antipsychotics such as olanzapine (OLZ) are associated with elevated blood glucose levels. Owing to serious cases of diabetic ketoacidosis and diabetic coma in Japan, OLZ is contraindicated in patients with diabetes, and blood glucose monitoring is advised even in non-diabetic cases. However, the precise mechanism of antipsychotic-induced hyperglycemia remains unclear; therefore, we investigated the role of hypothalamic adenosine 5′-monophosphate-activated protein kinase (AMPK) activity and adrenaline secretion in hyperglycemia induced by long-term OLZ administration. Additionally, we examined the potential effects of Oren-gedoku-to (OGT), a traditional Chinese medicine that suppresses hypothalamic AMPK activation, on hyperglycemia induced by chronic OLZ administration.
Materials and Methods: Female Wistar rats were divided into three treatment groups: saline (control), OLZ (20 mg/kg/d), and OLZ (20 mg/kg/d)/OGT (500 mg/kg/d). Each treatment was orally administered twice daily for 2 weeks. Blood glucose and adrenaline concentrations, as well as hypothalamic AMPK alpha and phosphorylated AMPK alpha activities, were measured and compared using the Tukey–Kramer multiple comparison test.
Results: Serum glucose and adrenaline levels were elevated in the OLZ group but not in the OLZ/OGT group. Furthermore, an increase in hypothalamic AMPK activity was observed in OLZ rats but not in OLZ/OGT rats.
Conclusion: Our results suggest that OGT administration inhibits hyperglycemia induced by chronic OLZ administration by suppressing increased AMPK activity and adrenaline secretion.

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