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Sci Rep. 2015 Nov 27;5:17310. doi: 10.1038/srep17310.

Therapeutic window of globular adiponectin against cerebral ischemia in diabetic mice: the role of dynamic alteration of adiponectin/adiponectin receptor expression.

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Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Department of Anesthesiology, Shaanxi Provincial Hospital, Xi'an 710068, China.
Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Department of Anesthesiology, School of Medicine, Stony Brook University, New York 11794-8480, USA.


Recent studies have demonstrated that adiponectin (APN) attenuates cerebral ischemic/reperfusion via globular adiponectin (gAD). However, the therapeutic role of gAD in cerebral ischemic injury in type 1 diabetes mellitus (T1DM) remains unclear. Our results showed that gAD improved neurological scores and reduced the infarct volumes in the 8-week T1DM (T1DM-8W) mice, but not in the 2-week T1DM (T1DM-2W) mice. Moreover, the ischemic penumbra APN levels increased and peaked in T1DM-2W mice, and reduced to normal in T1DM-8W mice, while the APN receptor 1 (AdipoR1) expression change was the opposite. Administration of rosiglitazone in T1DM-2W mice up-regulated the expression of AdipoR1 and restored the neuroprotection of gAD, while intracerebroventricular injection of AdipoR1 small interfering RNA (siRNA) in T1DM-8W mice reversed it. Furthermore, the expression of p-PERK, p-IRE1 and GRP78 were increased whereas the expressions of CHOP and cleaved caspase-12 as well as the number of apoptotic neurons were decreased after gAD treatment in T1DM-8W mice. These beneficial effects of gAD were reversed by pretreatment with AdipoR1 siRNA. These results demonstrated a dynamic dysfunction of APN/AdipoR1 accompanying T1DM progression. Interventions bolstering AdipoR1 expression during early stages and gAD supplementation during advanced stages may potentially reduce the cerebral ischemic injury in diabetic patients.

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