Abstract
Both Type 2 diabetes mellitus (T2DM) and estrogen deprivation have been shown to be associated with the development of cardiovascular disease and adverse cardiac remodeling. However, the role of estrogen deprivation on adverse cardiac remodeling in nonobese T2DM rats has not been clearly elucidated. We hypothesized that estrogen-deprivation aggravates adverse cardiac remodeling in Goto–Kakizaki (GK) rats. Wild-type (WT) and GK rats at the age of 9 months old were divided into two subgroups to have either a sham operation (WTS, GKS) or a bilateral ovariectomy (WTO, GKO) (n = 6/subgroup). Four months after the operation, the rats were killed, and the heart was excised rapidly. Metabolic parameters, cardiomyocytes hypertrophy, cardiac fibrosis, and biochemical parameters were determined. GK rats had hyperglycemia with hypoinsulinemia, and estrogen deprivation did not increase the severity of T2DM. Cardiac hypertrophy, cardiac oxidative stress, and phosphor-antinuclear factor κB were higher in WTO and GKS rats than WTS rats, and they markedly increased in GKO rats compared with GKS rats. Furthermore, cardiac fibrosis, transforming growth factor-β, Bax, phosphor-p38, and peroxisome proliferator- activated receptor γ coactivator-1α expression were increased in GKS and GKO rats compared with the lean rats. However, mitochondrial dynamics proteins including dynamin-related protein 1 and mitofusin-2 were not altered by T2DM and estrogen deprivation. Although estrogen deprivation did not aggravate T2DM in GK rats, it increased the severity of cardiac hypertrophy by provoking cardiac inflammation and oxidative stress in nonobese GK rats.
Highlights
Type 2 diabetes mellitus (T2DM) has been proposed as a global health problem [1]
In GK rats, both GK rats with sham operation (GKS) and GK ovariectomized rats (GKO) exhibited T2DM as indicated by increased plasma glucose and decreased plasma insulin compared with WTS rats (Table 1)
In OVX group, plasma cholesterol and low-density lipoprotein (LDL) levels were increased in both wild-type ovariectomized rats (WTO) and GKO rats, compared with their sham operation (Table 1)
Summary
Type 2 diabetes mellitus (T2DM) has been proposed as a global health problem [1]. In advanced state of uncontrolled T2DM patients, there is impaired pancreatic β-cell function, and diminished insulin sensitivity in the insulin responsive tissues including the heart [2], leading to hypoinsulinemia and hyperglycemia. Several experimental models have been use to replicate human T2DM such as db/db mice, Zucker diabetic rats, and Goto–Kakizaki (GK) rats. GK rats are genetically engineered nonobese rats with hyperglycemia and hypoinsulinemia, and have been used as a nonobese T2DM model [3]. Several pieces of evidence showed that GK rats have developed pathological conditions in the heart including cardiac dysfunction, hypertrophy, and fibrosis [4,5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
