Protective effects of desacyl ghrelin on diabetic cardiomyopathy.

Abstract

AIM:

Diabetic cardiomyopathy is a specific complication of type 2 diabetes mellitus, which causes progressive cardiac dysfunction. Desacyl ghrelin has been preliminarily demonstrated to have beneficial effects on cardiovascular system and glucose metabolism, which are both related to diabetic cardiomyopathy. The aim of this study was to investigate the protective effects of desacyl ghrelin on cardiac dysfunction, cardiac fibrosis, and cellular autophagy in a type 2 diabetic mouse model.

MATERIALS AND METHODS:

Fourteen- to eighteen-week-old db/db diabetic and db/+ non-diabetic mice were intraperitoneally treated with desacyl ghrelin at a dosage of 100 μg/kg for ten consecutive days. Ventricular fractional shortening was examined as an indicator of cardiac function by transthoracic echocardiography.

RESULTS:

The presence of diabetic cardiomyopathy was evident by the reduction in fractional shortening shown in our examined db/db mice. Intriguingly, this reduction in fractional shortening was not observed in the hearts of db/db mice treated with desacyl ghrelin. Cardiac fibrosis (indicated by excessive collagen deposition, decreased by Adiponectin and Mmp13 expression, and up-regulated by Mmp8 expression) and impairment of autophagic signalling (indicated by decreases in Foxo3 and LC3 II-to-LC3 I ratio) were shown in the hearts of diabetic mice. All these cellular and molecular alterations were alleviated by desacyl ghrelin treatment. The key cardiac pro-survival cellular signals including AMPK, Akt, ERK1/2, and GSK3α/β were impaired in the diabetic hearts, but the administration of desacyl ghrelin attenuated these signalling impairments.

CONCLUSIONS:

These results collectively demonstrate that desacyl ghrelin protects the heart against cardiac dysfunction in type 2 diabetic mice by inhibiting excessive collagen deposition and enhancing cardiac autophagic signalling via the pro-survival cellular AMPK/ERK1/2 signalling pathways.

• Authors: Xiao M Pei, Benjamin Y Yung, Shea P Yip, Lawrence W Chan, Cesar S Wong, Michael Ying, Parco M Siu
• Journal: Acta diabetologica (Acta Diabetol) Vol. 52 Issue 2 Pg. 293-306 (Apr 2015) ISSN: 1432-5233 [Electronic] Germany
• PMID: 25192951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Ghrelin
• ghrelin, des-n-octanoyl
• Matrix Metalloproteinase 8

Topics

• Adiponectin (genetics, metabolism)
• Animals
• Diabetes Mellitus, Type 2 (complications)
• Diabetic Cardiomyopathies (etiology, genetics, physiopathology, prevention & control)
• Disease Models, Animal
• Ghrelin (administration & dosage)
• Heart (physiopathology)
• Humans
• Male
• Matrix Metalloproteinase 8 (genetics, metabolism)
• Mice