Reviews in Endocrine & Metabolic Disorders最新文献

Obesity and type-2 diabetes mellitus (T2DM) are interrelated metabolic disorders primarily driven by overnutrition and physical inactivity, which oftentimes entails a transition from obesity to T2DM. Compromised musculoskeletal health consistently emerges as a common hallmark in the progression of these metabolic disorders. Skeletal muscle atrophy and dysfunction can further impair whole-body metabolism and reduce physical exercise capacity, thus instigating a vicious cycle that further deteriorates the underlying conditions. However, the myocellular repercussions of these metabolic disturbances remain to be completely clarified. Insulin signaling not only facilitates skeletal muscle glucose uptake but also plays a central role in skeletal muscle anabolism mainly due to suppression of catabolic pathways and facilitating an anabolic response to nutrient feeding. Chronic overnutrition may trigger different myocellular mechanisms proposed to contribute to insulin resistance and aggravate skeletal muscle atrophy and dysfunction. These mechanisms mainly include the inactivation of insulin signaling components through sustained activation of stress-related pathways, mitochondrial dysfunction, a shift to glycolytic skeletal muscle fibers, and hyperglycemia. In the present review, we aim to delve on these mechanisms, providing an overview of the myocellular processes involved in skeletal muscle atrophy and dysfunction under chronic overnutrition, and their contribution to the progression to T2DM.

Purpose: Hypoestrogenism is associated with loss of bone mass and strength. Melatonin has become a strategy due to its actions on bone tissue. This review summarizes the available data on the effects of chronic melatonin administration on bone tissue in animal models with hypoestrogenism.

Data sources: A systematic search of the PubMed, Web of Science, and Scopus, databases up to November 27, 2023, was conducted using specified key terms and Boolean operators (bone AND bones OR bone density OR bone diseases OR osteogenesis OR osteoporosis AND melatonin).

Study selection: only controlled studies in English and with rodents.

Study design: systematic review.

Data extraction: animals' characteristics (sex and hypoestrogenism confirmation), dose, route, and duration of administration of melatonin, and outcomes from the properties of bone.

Results: A total of 25 studies were identified after the screening process. In the hypoestrogenic state, melatonin administration improved bone mineral density, bone volume ratio, trabecular number in 19 studies, and maximal load/strength and stiffness test in 7. 4 studies reported improved matrix mineralization in bone marrow mesenchymal stem cells. Melatonin increased the expression of RUNX2 in 9 studies, OCN in 6, and OPG in 4, while decreasing RANKL in 3. In 4 studies the melatonin increased the serum osteocalcin levels.

Conclusion: Chronic administration of melatonin appears to improve the biophysical, biomechanical, molecular, and biochemical properties of bone tissue. These benefits promote an osteogenic effect, making melatonin an efficient strategy to preserve microarchitecture and tissue mass in a state of hypoestrogenism.

People with type 2 diabetes (T2D) have a 2-3-time higher risk of developing sarcopenia, a musculoskeletal disease marked by a progressive loss of skeletal muscle mass and strength, compared to people without T2D. This narrative review examines the effectiveness of lifestyle interventions in enhancing muscle mass and strength in people with T2D, emphasizing their growing importance with advancements in obesity treatments. PubMed and Google Scholar were utilized to identify the most relevant published studies based on the authors' knowledge. The maintenance of skeletal muscle strength and mass in people with T2D is becoming more prominent due to the advent of weight loss therapies such as low-energy diets, bariatric surgery and pharmacotherapies. Although the weight loss is to be commended, a large proportion (20-50%) of the weight loss comes from lean mass, indicative of a loss in muscle mass. There are currently no pharmacotherapies to increase, or mitigate the loss of, lean mass, with lifestyle strategies prominent in this arena. Resistance exercise is the most effective method to increase muscle mass and strength in people with T2D, but there is some evidence of an anabolic resistance. Aerobic exercise and increased dietary protein intake may result in small increases in muscle mass and strength, with no evidence of an anabolic resistance to these stimuli. Exercise and protein supplementation can increase, or aid in the retention of, muscle strength and mass in individuals with T2D, but further research is needed to explore their benefits in patients undergoing concomitant pharmaceutical and surgical treatments.

A Rathke's cleft cyst (RCC) is a remnant of the embryologic Rathke's pouch and a common pituitary lesion. A true RCC is lined with ciliated cuboidal or columnar epithelia with occasional goblet cells and squamous metaplasia. A RCC is frequently diagnosed incidentally through magnetic resonance imaging and computed tomography of the brain or pituitary gland. Presentation can range from an asymptomatic clinical picture to a rapidly progressive disease. RCC are located most often in the sellar and suprasellar regions and a careful differential diagnosis is crucial, especially to exclude craniophryngioma. Recent studies illuminate novel molecular mechanisms and markers for understanding the pathogenesis of RCC. PROP-1, a paired-like homeodomain transcription factor, controls pituitary ontogeny and its high expression induces RCCs. Both transgenic mouse models and immunohistochemical analysis of human RCCs indicate that the leukemia inhibitory factor is involved in pathogenesis. The expression of cytokeratins 8 and 2 in RCCs, but not in craniopharyngiomas, and the presence of beta-catenin mutations in many craniopharyngiomas, but not in RCCs, help with the differential diagnosis. For asymptomatic and small RCCs, observation is appropriate, with serial magnetic resonance imaging and hormonal investigation depending on the patient's clinical status. Surgical resection may be required for symptomatic RCC and recurrence rates are generally low. For patients with a recurrence, stereotactic radiosurgery is an effective approach with low risk.

The hypothalamic polypeptide growth hormone-releasing hormone (GHRH) stimulates the secretion of growth hormone (GH) from the pituitary through binding and activation of the pituitary type of GHRH receptor (GHRH-R), which belongs to the family of G protein-coupled receptors with seven potential membrane-spanning domains. Various splice variants of GHRH-R (SV) in human neoplasms and other extrapituitary tissues were demonstrated and their cDNA was sequenced. Among the SVs, splice variant 1 (SV1) possesses the greatest similarity to the full-length GHRH-R and remains functional by eliciting cAMP signaling and mitogenic activity upon stimulation by GHRH. In this review, we briefly discuss the activation, regulation, molecular mechanisms and signaling pathways of GHRH-Rs and their SVs in various tissues and also summarize the expression, biological activities and potential function of GHRH, its analogs and their receptors. A large body of work have extensively studied and evaluated potential clinical applications of agonists and antagonists of GHRH in diverse fields, including oncology, endocrinology, obesity, diabetes, other metabolic dysfunctions, cardiology, immune functions, mood disorders, Alzheimer's and lung disease, ophthalmology, inflammation, wound healing and other applications. These results strongly support the potential therapeutic use of GHRH analogs in human medicine in the near future.

The global prevalence of obesity among elderly patients continues to rise. Despite the availability of new antiobesity medications, bariatric surgery remains an effective treatment option for carefully selected candidates. However, it is not risk-free, especially in a vulnerable population, predisposing to falls, fractures and sarcopenia. Following bariatric surgery, there is rapid loss of muscle mass, particularly within the first 3 months. Muscle quality, on the other hand, characterized by functionality and indirectly assessed through strength tests, appears to be preserved. This is attributed to reductions in ectopic intramuscular fat deposits. Strategies to mitigate muscle loss and functional impairment include combined exercises (resistive and aerobic training), adequate protein and vitamin D intake, beta-hydroxy-beta-methylbutyrate (HMB) supplementation, and testosterone replacement therapy for men with confirmed hypogonadism. It is important to emphasize that, to date, no specific trial has evaluated the current sarcopenia criteria in elderly patients undergoing bariatric surgery. Therefore, future studies are needed to assess this particularly vulnerable population, not only to monitor changes in muscular health, but also to develop strategies for preventing therapeutic inertia.

The prostate gland is an endocrine-sensitive organ responding to multiple stimuli. Its development and function are regulated by multiple hormones (i.e. steroids such as androgens, estrogens and glucocorticoids) but also by other key hormonal systems such as those comprised by insulin-like growth factor 1 and insulin, which are sourced by different tissues [e.g. testicles/adrenal-gland/adipose-tissue/liver/pancreas, etc.). Particularly important for the endocrine control of prostatic pathophysiology and anatomy are hormones produced and/or secreted by different cell types of the pituitary gland [growth-hormone, luteinizing-hormone, follicle-stimulating hormone, and prolactin, oxytocin, arginine-vasopressin and melanocyte-stimulating hormone], which affect prostate gland function either directly or indirectly under physiological and pathophysiological conditions [e.g. metabolic dysregulation (e.g. obesity), and prostate transformations (e.g. prostate cancer)]. This review summarizes the impact of all pituitary hormone types on prostate gland under these diverse conditions including in vivo and in vitro studies.

Despite initial discovery in pancreatic tumors, GHRH is a 44-amino acid peptide primarily expressed in the hypothalamus. Recent RNA sequencing clarifies GHRH expression: predominantly hypothalamic in humans, with some basal ganglia presence, while extending to additional central nervous system (CNS) regions in other species. GHRH binds to its G-protein coupled receptor (GHRHR) in the arcuate (ARC), ventromedial (VMH), and periventricular (PeN) nuclei of the hypothalamus to exert its effects. Notably, the highest non-brain expression is found in somatotroph cells of the pituitary, directly targeting growth hormone (GH) production. GHRH is the primary regulator of pulsatile GH secretion, counteracted by somatostatin. While early models proposed alternating GHRH/somatostatin bursts, others implicate somatostatin as the primary regulator of GH pulse timing. These models fail to fully explain species and gender differences, particularly regarding nutritional status. The discovery of ghrelin, acting via GHS-R1a on GHRH neurons, significantly advanced understanding of GH regulation. Ghrelin interacts intricately with GHRH, modulating its expression and neuronal activity. Ghrelin also exerts GHRH-independent GH stimulation and synergizes with GHRH. The crucial role of GHRH in GH regulation is demonstrated by its key involvement in the action of other GH regulators, such as leptin, neuropeptide Y (NPY), and orexins. However, these interactions have also revealed that the physiological effects of GHRH extend far beyond its canonical role as a GH secretagogue. In this context, GHRH is thought to be a key regulator of the sleep-wake cycle and may be involved in whole-body energy homeostasis. The objective of this review is to summarize the current knowledge on GHRH and to discuss the potential pleiotropic effect of this hypothalamic neuropeptide, far beyond its classical action as regulator of the somatotroph axis.

Multiple guidelines for thyroid nodule management have been developed by endocrinologists, often in collaboration with surgeons and radiologists. While there is now a lot of scientific information available to meet the needs of healthcare providers, there is not always uniformity and standardization among recommendations. Consequently, the interpretation and application of guidelines in clinical practice remain somewhat limited. In this context, the management of "small" thyroid nodule warrants full discussion. Looking at treatment guidelines, surgery is the first-line option and the risk of cancer relapse can be assessed only after at least thyroidectomy; in addition, according to guidelines of minimally invasive treatment, thermal ablation may be considered for patients with small classical papillary carcinoma. However, the Thyroid Imaging Reporting And Data Systems do not recommend biopsy in nodules less than 1 cm; and performing biopsy may yield a result that is suspicious or consistent with malignancy without specifying the cancer subtype. With these premises, facing cases of "small" nodule less than 1 cm is challenging. Even if the recommendations of guidelines sound singularly appropriate, they may seem conflicting. Coordinated guidelines are needed.

The prevalence of type-2 diabetes mellitus (T2DM) has increased over 10-fold in the past 40 years in China, which now has the largest T2DM population in the world. Insulin resistance and β-cell dysfunction are the typical features of T2DM. Although both factors play a role, decreased β-cell function and β-cell mass are the predominant factors for progression to T2DM. Considering the differences between Chinese T2DM patients and those of other ethnicities, it is important to characterize β-cell dysfunction in Chinese patients during T2DM progression. Herein, we reviewed the studies on the relationships between β-cell function and T2DM progression in the Chinese population and discussed the differences among individuals of varying ethnicities. Meanwhile, we summarized the risk factors and current treatments of T2DM in Chinese individuals and discussed their impacts on β-cell function with the hope of identifying a better T2DM therapy.