Related Experiment Video
Updated: Mar 21, 2026
Osmotic Minipump Implantation for Increasing Glucose Concentration in Mouse Cerebrospinal Fluid
Published on: April 7, 2023
Elevated Expression of Carboxy-Terminal Modulator Protein (CTMP) Aggravates Brain Ischemic Injury in Diabetic db/db
Yu Chen1,2, Min Cai1,2, Jiao Deng1,2
1Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Abstract:
Deregulation of Akt signaling is important in the brain injuries caused by cerebral ischemia in diabetic animals, and the underlying mechanism is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following focal cerebral ischemia in type 2 diabetic db/db mice and their control littermates non-diabetic db/+ mice. db/db mice showed a significant elevation in the expression of CTMP compared to db/+ mice under normal physiological conditions. After ischemia, db/db mice exhibit higher levels of CTMP expression, decreased Akt kinase activity, adverse neurological deficits and cerebral infarction than db/+ mice. To further certain the effectiveness of Akt signaling to the final outcome of cerebral ischemia, the animals were treated with LY294002, an inhibitor of the Akt pathway, which aggravated the ischemic injury in db/+ mice but not in db/db mice. RNA interference-mediated depletion of CTMP were finally applied in db/db mice, which restored Akt activity, improved neurological scores and reduced infarct volume. These results suggest that elevation of CTMP in diabetic mice suppresses Akt activity and ultimately negatively affects the outcome of ischemia. Inhibitors specifically targeting CTMP may be beneficial in the treatment of cerebral ischemia in patients with diabetes.
Insights
Diabetic mice show elevated CTMP, inhibiting Akt signaling and worsening brain injury after stroke. Reducing CTMP improved outcomes, suggesting CTMP inhibitors could treat diabetic stroke patients.
Area of Science:
- Neuroscience
- Endocrinology
- Pathophysiology
Background:
- Akt signaling pathway dysregulation is implicated in diabetic brain injuries from cerebral ischemia.
- The precise mechanisms, particularly the role of endogenous Akt inhibitors, remain unclear.
Purpose of the Study:
- To investigate the role of carboxy-terminal modulator protein (CTMP) in cerebral ischemia-induced brain injury in type 2 diabetic mice.
- To elucidate the impact of CTMP on Akt signaling and neurological deficits in diabetic conditions.
Main Methods:
- Comparison of CTMP expression and Akt activity between diabetic (db/db) and non-diabetic (db/+) mice following focal cerebral ischemia.
- Pharmacological inhibition of the Akt pathway using LY294002.
- RNA interference-mediated depletion of CTMP in db/db mice.
Main Results:
- Diabetic db/db mice exhibited significantly higher CTMP expression and lower Akt activity compared to controls.
- Ischemia led to exacerbated neurological deficits and larger infarct volumes in db/db mice.
- CTMP depletion in db/db mice restored Akt activity, improved neurological scores, and reduced infarct size.
Conclusions:
- Elevated CTMP in diabetic mice suppresses Akt activity, worsening cerebral ischemia outcomes.
- Targeting CTMP with specific inhibitors may offer a therapeutic strategy for cerebral ischemia in diabetic patients.
