Objective
In men, androgen deprivation contributes to the development of metabolic syndrome and type 2 diabetes (T2D). In women, androgen excess predisposes to insulin resistance and T2D. There is a ...bidirectional modulation of glucose homeostasis by androgens in males and females that is analyzed in this review.
Methods
We reviewed the literature in both rodents and humans on the role of androgens and the androgen receptor (AR) in the control of glucose and energy metabolism in health, obesity, and T2D.
Results
Sex‐specific activation of AR in the hypothalamus, skeletal muscle, liver, adipose tissue, and pancreatic islet β‐cells accounts for maintenance or disruption in energy metabolism and glucose homeostasis.
Conclusions
We argue that AR is a target to prevent androgen‐related metabolic disorders.
Abstract
The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome ...coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.
Coronavirus disease 2019 (COVID-19) is a novel threat that seems to result from the collusion between a new pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and an existing ...pandemic of metabolic disease driven by obesity. This Perspective explores the evolving epidemiological, clinical, biological, and molecular evidence to propose an unfolding paradigm in which old age, chronic metabolic disease (such as obesity, type 2 diabetes, and metabolic syndrome), and male biological sex produce a deadly symbiosis of dysregulated immunometabolism and chronic systemic inflammation that intensifies virally induced hyperinflammation associated with SARS-CoV-2 infection. It is intended to inspire new research directions and stimulate funding in this field.
Some aspects of glucose homeostasis are regulated differently in males and females. This review discusses the most fundamental gender differences in glucose homeostasis and diabetes. These include ...the prevalence of impaired fasting glucose and impaired glucose tolerance, the prevalence and incidence of type 2 and type 1 diabetes, and the sex-specific effects of testosterone and estrogen deficiency and excess. These gender-specific differences in glucose homeostasis represent a source of factors that should be studied to develop gender-based therapeutic avenues for diabetes.
•Following an oral glucose challenge, women have lower fasting plasma glucose and higher 2-hour plasma glucose than men.•Impaired fasting glucose is more prevalent in men while impaired glucose tolerance is more prevalent in women.•Type 1 diabetes is the only common autoimmune disease not characterized by female predominance and exhibits an increased male bias after puberty.•Estrogen deficiency and/or testosterone excess predisposes women to type 2 diabetes•Testosterone deficiency predisposes men to type 2 diabetes.
Estrogens play a fundamental role in the physiology of the reproductive, cardiovascular, skeletal, and central nervous systems. In this report, we review the literature in both rodents and humans on ...the role of estrogens and their receptors in the control of energy homeostasis and glucose metabolism in health and metabolic diseases. Estrogen actions in hypothalamic nuclei differentially control food intake, energy expenditure, and white adipose tissue distribution. Estrogen actions in skeletal muscle, liver, adipose tissue, and immune cells are involved in insulin sensitivity as well as prevention of lipid accumulation and inflammation. Estrogen actions in pancreatic islet β-cells also regulate insulin secretion, nutrient homeostasis, and survival. Estrogen deficiency promotes metabolic dysfunction predisposing to obesity, the metabolic syndrome, and type 2 diabetes. We also discuss the effect of selective estrogen receptor modulators on metabolic disorders.
The current novel coronavirus disease 2019 (COVID-19) pandemic is revealing profound differences between men and women in disease outcomes worldwide. In the United States, there has been inconsistent ...reporting and analyses of male-female differences in COVID-19 cases, hospitalizations, and deaths. We seek to raise awareness about the male-biased severe outcomes from COVID-19, highlighting the mechanistic differences including in the expression and activity of angiotensin-converting enzyme 2 (ACE2) as well as in antiviral immunity. We also highlight how sex differences in comorbidities, which can be associated with both age and race, impact male-biased outcomes from COVID-19.
Objective
Androgen excess in women is associated with visceral adiposity. However, little is known on the mechanism through which androgen promotes visceral fat accumulation.
Methods
To address this ...issue, female mice to chronic androgen excess using 5α‐dihydrotestosterone (DHT) and studied the regulation of energy homeostasis was exposed.
Results
DHT induced a leptin failure to decrease body weight associated with visceral adiposity but without alterations in leptin anorectic action. This paralleled leptin's failure to upregulate brown adipose tissue expression of uncoupling protein‐1, associated with decreased energy expenditure (EE). DHT decreased hypothalamic proopiomelanocortin (pomc) mRNA expression and increased POMC intensity in neuronal bodies of the arcuate nucleus while simultaneously decreasing the intensity of POMC projections to the dorsomedial hypothalamus (DMH). This was associated with a failure of the melanocortin 4 receptor agonist melanotan‐II to suppress body weight.
Conclusion
Taken together, these data indicate that androgen excess promotes visceral adiposity with reduced POMC neuronal innervation in the DMH, reduced EE but without hyperphagia.
There are fundamental aspects of the control of metabolic homeostasis that are regulated differently in males and females. This sex asymmetry represents an evolutionary paradigm for females to resist ...the loss of energy stores. This perspective discusses the most fundamental sex differences in metabolic homeostasis, diabetes, and obesity. Together, the role of genetic sex, the programming effect of testosterone in the prenatal period in males, and the activational role of sex hormones at puberty produce two different biological systems in males and females that need to be studied separately. These sex-specific differences in energy homeostasis and metabolic dysfunction represent an untested source of factors that can be harnessed to develop relevant sex-based therapeutic avenues for diabetes, metabolic syndrome, and obesity.
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