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Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms.
Cardiovasc Diabetol. 2012 Oct 15; 11:129.CD

Abstract

BACKGROUND

The aim of this study was to investigate whether obestatin (OB), a peptide mediator encoded by the ghrelin gene exerting a protective effect in ischemic reperfused heart, is able to reduce cardiac dysfunctions in adult diabetic rats.

METHODS

Diabetes was induced by STZ injection (50 mg/kg) in Wistar rats (DM). OB was administered (25 μg/kg) twice a day for 6 weeks. Non-diabetic (ND) rats and DM rats were distributed into four groups: untreated ND, OB-treated ND, untreated DM, OB-treated DM. Cardiac contractility and β-adrenergic response were studied on isolated papillary muscles. Phosphorylation of AMPK, Akt, ERK1/2 and GSK3β as well β-1 adrenoreceptors levels were detected by western blot, while α-MHC was measured by RT-PCR.

RESULTS

OB preserved papillary muscle contractility (85 vs 27% of ND), β-adrenergic response (103 vs 65% of ND), as well β1-adrenoreceptors and α-MHC levels in diabetic myocardial tissue. Moreover, OB up-regulated the survival kinases Akt and ERK1/2, and enhanced AMPK and GSK3β phosphorylation. OB corrected oxidative unbalance, reduced pro-inflammatory cytokine TNF-α plasma levels, NFkB translocation and pro-fibrogenic factors expression in diabetic myocardium.

CONCLUSIONS

OB displays a significant beneficial effect against the alterations of contractility and β-adrenergic response in the heart of STZ-treated diabetic rats, which was mainly associated with the ability of OB to up-regulate the transcription of β1-adrenergic receptors and α-MHC; this protective effect was accompanied by the ability to restore oxidative balance and to promote phosphorylation/modulation of AMPK and pro-survival kinases such as Akt, ERK1/2 and GSK3β.

Authors+Show Affiliations

Department of Experimental Medicine and Oncology, University of Turin, Corso Raffaello 30, Turin, 10125, Italy. manuela.aragno@unito.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23066908

Citation

Aragno, Manuela, et al. "Obestatin Induced Recovery of Myocardial Dysfunction in Type 1 Diabetic Rats: Underlying Mechanisms." Cardiovascular Diabetology, vol. 11, 2012, p. 129.
Aragno M, Mastrocola R, Ghé C, et al. Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms. Cardiovasc Diabetol. 2012;11:129.
Aragno, M., Mastrocola, R., Ghé, C., Arnoletti, E., Bassino, E., Alloatti, G., & Muccioli, G. (2012). Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms. Cardiovascular Diabetology, 11, 129. https://doi.org/10.1186/1475-2840-11-129
Aragno M, et al. Obestatin Induced Recovery of Myocardial Dysfunction in Type 1 Diabetic Rats: Underlying Mechanisms. Cardiovasc Diabetol. 2012 Oct 15;11:129. PubMed PMID: 23066908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Obestatin induced recovery of myocardial dysfunction in type 1 diabetic rats: underlying mechanisms. AU - Aragno,Manuela, AU - Mastrocola,Raffaella, AU - Ghé,Corrado, AU - Arnoletti,Elisa, AU - Bassino,Eleonora, AU - Alloatti,Giuseppe, AU - Muccioli,Giampiero, Y1 - 2012/10/15/ PY - 2012/07/06/received PY - 2012/09/21/accepted PY - 2012/10/17/entrez PY - 2012/10/17/pubmed PY - 2013/3/21/medline SP - 129 EP - 129 JF - Cardiovascular diabetology JO - Cardiovasc Diabetol VL - 11 N2 - BACKGROUND: The aim of this study was to investigate whether obestatin (OB), a peptide mediator encoded by the ghrelin gene exerting a protective effect in ischemic reperfused heart, is able to reduce cardiac dysfunctions in adult diabetic rats. METHODS: Diabetes was induced by STZ injection (50 mg/kg) in Wistar rats (DM). OB was administered (25 μg/kg) twice a day for 6 weeks. Non-diabetic (ND) rats and DM rats were distributed into four groups: untreated ND, OB-treated ND, untreated DM, OB-treated DM. Cardiac contractility and β-adrenergic response were studied on isolated papillary muscles. Phosphorylation of AMPK, Akt, ERK1/2 and GSK3β as well β-1 adrenoreceptors levels were detected by western blot, while α-MHC was measured by RT-PCR. RESULTS: OB preserved papillary muscle contractility (85 vs 27% of ND), β-adrenergic response (103 vs 65% of ND), as well β1-adrenoreceptors and α-MHC levels in diabetic myocardial tissue. Moreover, OB up-regulated the survival kinases Akt and ERK1/2, and enhanced AMPK and GSK3β phosphorylation. OB corrected oxidative unbalance, reduced pro-inflammatory cytokine TNF-α plasma levels, NFkB translocation and pro-fibrogenic factors expression in diabetic myocardium. CONCLUSIONS: OB displays a significant beneficial effect against the alterations of contractility and β-adrenergic response in the heart of STZ-treated diabetic rats, which was mainly associated with the ability of OB to up-regulate the transcription of β1-adrenergic receptors and α-MHC; this protective effect was accompanied by the ability to restore oxidative balance and to promote phosphorylation/modulation of AMPK and pro-survival kinases such as Akt, ERK1/2 and GSK3β. SN - 1475-2840 UR - https://www.unboundmedicine.com/medline/citation/23066908/Obestatin_induced_recovery_of_myocardial_dysfunction_in_type_1_diabetic_rats:_underlying_mechanisms_ L2 - https://cardiab.biomedcentral.com/articles/10.1186/1475-2840-11-129 DB - PRIME DP - Unbound Medicine ER -