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There is growing evidence that fat accumulation in the pancreas can have consequences for metabolic health. This Review discusses the methods for detecting pancreatic fat and the potential causes and pathogenic consequences of pancreatic fat accumulation.
Within the pancreatic islets of Langerhans, endocrine cells are heterogeneous in terms of transcriptional profile, protein expression and the regulation of hormone release. This Review describes how endocrine cell heterogeneity, particularly of β-cells, affects the regulation of hormone secretion within pancreatic islets.
This Review highlights the ontogeny of thermogenic adipocytes, regulation of the adipose tissue microenvironment and inter-organ communication between adipose and other tissues. In addition, activation of thermogenic adipose tissue in humans and animal models is discussed, as well as the therapeutic potential of thermogenic adipose tissue.
Melanin-concentrating hormone (MCH) integrates physiological functions and mood states associated with energy and glucose homeostasis. In this Review, Al-Massadi et al. describe how MCH regulates the hedonic component of food intake and discuss its potential as a therapeutic target.
This Review outlines the pathogenesis of skeletal fragility in patients with type 2 diabetes mellitus, and discusses potential therapeutic approaches to the management of increased fracture risk in these patients. The evidence that skeletal fragility should now be included in the list of well-recognized diabetic complications is also summarized.
The cellular consequences of dysfunctional autophagy contribute to numerous diseases. In this Review, Kitada and Koya consider the relationship between impaired autophagy and age-related metabolic derangements, including insulin resistance, type 2 diabetes mellitus and sarcopenic obesity, and discuss candidate autophagy-based therapies.
Anterior pituitary tumours (APTs) are usually benign but sometimes exhibit aggressive behaviour. In very rare cases, they metastasize and are termed pituitary carcinomas. Here, the authors provide an overview of APTs and pituitary carcinomas, including their epidemiology, diagnosis, predictive markers, and current and emerging therapeutic approaches.
In children, growth hormone deficiency (GHD) results in growth failure and has multiple different causes. This Review discusses the diagnosis of GHD in children and highlights advances in management, including transitional care.
Although sexual dimorphism of the liver is well known, its contribution to non-alcoholic fatty liver disease (NAFLD) is often overlooked. Here, Lefebvre and Staels discuss liver sexual dimorphism in the context of increasingly accurate studies of cellular modifications in NAFLD.
It is 100 years since the famous experiments that identified insulin and showed that this protein could be used to treat people with type 1 diabetes mellitus. This Review charts the developments in insulin research over the past century and highlights future directions for this field.
The expression of growth differentiation factor 15 (GDF15) is increased under conditions of cellular stress as well as by metformin and exercise. This Review highlights mechanisms of GDF15 production and secretion, GDF15 signalling, and the relevance of GDF15 in obesity and metabolic diseases.
Transgender and gender-diverse (TGD) youth are increasingly seeking medical services to bring their physical sex characteristics into alignment with their gender identity. This Review highlights advances in our understanding of TGD youth, the challenges of providing gender-affirming care and research priorities.
Sex differences can have important implications in research and medical care. This Review will outline our understanding on sex differences, and will offer strategies that, if implemented, will provide information with which to personalize and improve health care for all people.
Bariatric surgery is linked with adverse effects on mental health in some patients. This Review summarizes how gut physiology changes after surgery and considers how alterations in gut-derived hormones, microbiota and bile acids can affect gut–brain signalling, with potential consequences for mood and behaviour.
Polycystic ovary syndrome (PCOS) is a common disorder of unclear aetiology. Although genetic factors contribute to PCOS, they only partially account for its heritability. Here, Stener-Victorin and Deng discuss the evidence that altered epigenetic and developmental programming influence the pathogenesis and familial transmission of PCOS.
Pituitary tumours are treated with stable analogues of somatostatin and dopamine, which respectively bind to somatostatin receptor types 2 and 5 (SST2 and SST5) and dopamine receptor type 2 (DRD2). This Review discusses SST and DRD2 signalling and its clinical importance in treatment resistance.
The management of type 2 diabetes mellitus (T2DM) in older adults (aged ≥65 years) presents specific challenges. This Review summarizes the key age-related mechanisms contributing to T2DM and evaluates new evidence relating to frailty and sarcopenia, hypoglycaemia, comorbidities, and the implications for existing guidelines and therapeutic options.
This Review summarizes the mechanisms by which endoplasmic reticulum (ER) stress contributes to β-cell dysfunction and cell death in monogenic diabetes and type 2 diabetes mellitus (T2DM). In addition, the potential therapeutic strategies for T2DM and metabolic syndrome that target ER stress in β-cells are discussed.
Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are closely linked; effective therapeutics are lacking for both conditions, particularly NAFLD. This Review will discuss therapeutic options for NAFLD, focusing on targeting intermediary metabolism, insulin resistance and T2DM.
This Review critically evaluates the studies that support and refute the role of brain insulin in systemic nutrient partitioning. The authors discuss the role of brain insulin in metabolic control and the contribution of brain insulin resistance to metabolic disease and assess the therapeutic potential of enhancing or restoring brain insulin signalling in metabolic disease.
