Nature Reviews Endocrinology

Imaging is an essential tool in research, diagnostics and the management of endocrine disorders. Ultrasonography, nuclear medicine techniques, MRI, CT and optical methods are already used for applications in endocrinology. Optoacoustic imaging, also termed photoacoustic imaging, is emerging as a method for visualizing endocrine physiology and disease at different scales of detail: microscopic, mesoscopic and macroscopic. Optoacoustic contrast arises from endogenous light absorbers, such as oxygenated and deoxygenated haemoglobin, lipids and water, or exogenous contrast agents, and reveals tissue vasculature, perfusion, oxygenation, metabolic activity and inflammation. The development of high-performance optoacoustic scanners for use in humans has given rise to a variety of clinical investigations, which complement the use of the technology in preclinical research. Here, we review key progress with optoacoustic imaging technology as it relates to applications in endocrinology; for example, to visualize thyroid morphology and function, and the microvasculature in diabetes mellitus or adipose tissue metabolism, with particular focus on multispectral optoacoustic tomography and raster-scan optoacoustic mesoscopy. We explain the merits of optoacoustic microscopy and focus on mid-infrared optoacoustic microscopy, which enables label-free imaging of metabolites in cells and tissues. We showcase current optoacoustic applications within endocrinology and discuss the potential of these technologies to advance research and clinical practice.

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The role of biomineralization in disorders of skeletal development and tooth formation

Christopher S. Kovacs, Catherine Chaussain, Philip Osdoby, Maria Luisa Brandi, Bart Clarke & Rajesh V. Thakker

doi : 10.1038/s41574-021-00488-z

Nature Reviews Endocrinology volume 17, pages336–349 (2021)

The major mineralized tissues are bone and teeth, which share several mechanisms governing their development and mineralization. This crossover includes the hormones that regulate circulating calcium and phosphate concentrations, and the genes that regulate the differentiation and transdifferentiation of cells. In developing endochondral bone and in developing teeth, parathyroid hormone-related protein (PTHrP) acts in chondrocytes to delay terminal differentiation, thereby increasing the pool of precursor cells. Chondrocytes and (in specific circumstances) pre-odontoblasts can also transdifferentiate into osteoblasts. Moreover, bone and teeth share outcomes when affected by systemic disorders of mineral homeostasis or of the extracellular matrix, and by adverse effects of treatments such as bisphosphonates and fluoride. Unlike bone, teeth have more permanent effects from systemic disorders because they are not remodelled after they are formed. This Review discusses the normal processes of bone and tooth development, followed by disorders that have effects on both bone and teeth, versus disorders that have effects in one without affecting the other. The takeaway message is that bone specialists should know when to screen for dental disorders, just as dental specialists should recognize when a tooth disorder should raise suspicions about a possible underlying bone disorder.

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Metabolic pathways in obesity-related breast cancer

Kristy A. Brown

doi : 10.1038/s41574-021-00487-0

Nature Reviews Endocrinology volume 17, pages350–363 (2021)

This Review focuses on the mechanistic evidence for a link between obesity, dysregulated cellular metabolism and breast cancer. Strong evidence now links obesity with the development of 13 different types of cancer, including oestrogen receptor-positive breast cancer in postmenopausal women. A number of local and systemic changes are hypothesized to support this relationship, including increased circulating levels of insulin and glucose as well as adipose tissue-derived oestrogens, adipokines and inflammatory mediators. Metabolic pathways of energy production and utilization are dysregulated in tumour cells and this dysregulation is a newly accepted hallmark of cancer. Dysregulated metabolism is also hypothesized to be a feature of non-neoplastic cells in the tumour microenvironment. Obesity-associated factors regulate metabolic pathways in both breast cancer cells and cells in the breast microenvironment, which provides a molecular link between obesity and breast cancer. Consequently, interventions that target these pathways might provide a benefit in postmenopausal women and individuals with obesity, a population at high risk of breast cancer.

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Novel therapies with precision mechanisms for type 2 diabetes mellitus

Leigh Perreault, Jay S. Skyler & Julio Rosenstock

doi : 10.1038/s41574-021-00489-y

Nature Reviews Endocrinology volume 17, pages364–377 (2021)

Type 2 diabetes mellitus (T2DM) is one of the greatest health crises of our time and its prevalence is projected to increase by >50% globally by 2045. Currently, 10 classes of drugs are approved by the US Food and Drug Administration for the treatment of T2DM. Drugs in development for T2DM must show meaningful reductions in glycaemic parameters as well as cardiovascular safety. Results from an increasing number of cardiovascular outcome trials using modern T2DM therapeutics have shown a reduced risk of atherosclerotic cardiovascular disease, congestive heart failure and chronic kidney disease. Hence, guidelines have become increasingly evidence based and more patient centred, focusing on reaching individualized glycaemic goals while optimizing safety, non-glycaemic benefits and the prevention of complications. The bar has been raised for novel therapies under development for T2DM as they are now expected to achieve these aims and possibly even treat concurrent comorbidities. Indeed, the pharmaceutical pipeline for T2DM is fertile. Drugs that augment insulin sensitivity, stimulate insulin secretion or the incretin axis, or suppress hepatic glucose production are active in more than 7,000 global trials using new mechanisms of action. Our collective goal of being able to truly personalize medicine for T2DM has never been closer at hand.

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