title: Therapeutic window of globular adiponectin against cerebral ischemia in diabetic mice: the role of dynamic alteration of adiponectin/adiponectin receptor expression.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.|Department of Anesthesiology, Shaanxi Provincial Hospital, Xi'an 710068, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Haixing
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Anesthesiology, School of Medicine, Stony Brook University, New York 11794-8480, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Shaanxi Provincial Hospital, Xi'an 710068, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Lize
authors.initials: L
authors.lastname: Xiong
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D053454:Caspase 12; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D054419:Receptors, Adiponectin; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C499919:Adipoq protein, mouse; C497250:Ddit3 protein, mouse; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse; C475419:adiponectin receptor 1, mouse; C486556:Ern2 protein, mouse; C506440:Casp12 protein, mouse