Oestrogen may protect diabetes patients from cardiomyopathy, according to research published in Circulation: Heart Failure. The study showed that severe insulin resistance in the heart causes cardiomyopathy and death in male mice, but also showed that oestrogen protected female mice.
“Cardiovascular disease is the major cause of morbidity and mortality for diabetic patients,” explained Shaodong Guo, PhD, primary investigator for the study at Texas A&M.
“Previous studies have shown that while there’s a lower instance of both cardiovascular disease and Type 2 diabetes in premenopausal women than in their age-matched male counterparts, these incidences rise sharply after female menopause,” Prof Guo said.
This indicates that the ovaries and ovarian hormones, such as oestrogen, may protect from Type 2 diabetes and cardiovascular diseases, he said.
The study investigated the role of ovaries and oestrogen in cardiac function and energy metabolism with mice who had the the cardiac insulin receptor substrate, IRS, modified or suppressed to mimic cardiac insulin resistance.
“Our previous studies reported that impaired cardiac insulin signalling with loss of insulin receptor substrate IRS1 and IRS2 genes leads to death of male mice,” he said. “In this study, we wanted to know how the removal of the ovaries might affect cardiomyopathy in female mice and also what other impacts the loss of insulin receptors might have on energy metabolism and mitochondrial function.”
Insulin resistance and signaling
About 90–95% of patients with Type 2 diabetes suffer from insulin resistance, a risk factor for heart failure. In healthy tissue, insulin binds to insulin receptors, activating a network of intracellular signalling pathways. Disruptions in these signalling pathways have been linked to mitochondrial dysfunction, cardiomyopathy, and impaired glucose and fatty acid metabolism, among other health issues.
In this study, mice lacking IRS developed dilated cardiomyopathy, and analysis showed lowered activity of genes important for mitochondrial function and energy metabolism.
“Type 2 diabetes patients and insulin-resistant patients exhibit mitochondrial dysfunction,” Prof Guo explained.
The study fills in some blanks in understanding the role of insulin and estrogen signaling in mitochondrial function.
Study findings
Guo said there were four important findings from the study:
- All female mice that lacked insulin receptor substrates survived for more than a year.
- Female mice without insulin receptor substrates were less likely to experience severe cardiac dysfunction and death if they had ovaries. If the mice also lacked ovaries but received oestrogen, it prolonged their lifespans. Doses of oestrogen also protected IRS-altered male mice from heart dysfunction.
Guo said oestrogen also prevents cardiomyopathy induced by loss of cardiac insulin receptor substrates.
“And removal of the ovaries leads to the death of female cardiac IRS1 and IRS2 double genes knockout mice if there is no reintroduction of oestrogen,” he said.
Loss of IRS1 and IRS2 genes in heart tissue disrupts cardiac energy metabolism, gene activity involved in mitochondrial function, and whole-body energy metabolism. However, oestrogen partially reverses these effects.
Oestrogen is important for healthy cellular signalling pathways and promotes mitochondrial function.
Prof Guo said the study shows that oestrogen enhances cardiac function, promotes energy metabolism, prevents cardiomyopathy and prolongs survival in both male and ovariectomy female mice lacking the insulin receptor substrates.
“This study provides evidence for the gender difference for the incidence of cardiovascular disease and implies that oestrogen replacement therapy is feasible for the treatment of diabetic cardiomyopathy through enhancement of mitochondrial function and energy metabolism,” he said. “It also reveals some of the signalling pathways that may be potential therapeutic targets for the prevention or treatment of cardiovascular diseases in patients with Type 2 diabetes.”
Guo also noted that diet could also play a role with oestrogens in foods.
“The study implies that food-derived oestrogens or phytoestrogens may play similar roles to oestrogen, as observed in mice,” he said. “This may help us reshape our knowledge of nutrient and food sciences related to plant hormones that can modulate chronic metabolic diseases such as Type 2 diabetes and associated cardiovascular complications.”
Source: Texas A&M University
