Reviews & Analysis

Cancer cells consume and utilize glucose at a higher rate than normal cells. However, some microenvironments limit the availability of nutrients and glucose. In 2018, researchers found that tumours depend on a variety of different nutrient sources, both locally and systemically, to overcome metabolic limitations and promote tumour progression and metastasis.

Insulin resistance is a main determinant in the development of type 2 diabetes mellitus. Here, the authors review the physiological links between circadian clocks and insulin sensitivity and present current evidence for a relationship between circadian disruption and insulin resistance.

Type 2 diabetes mellitus and obesity are major public health challenges; emerging evidence suggests that melatonin is involved in the development of these disorders, opening new avenues for research. This Review discusses the effect of melatonin and its receptors on glucose homeostasis, obesity and type 2 diabetes mellitus.

Loss or dysfunction of β-cells is a characteristic of insulin-dependent diabetes mellitus. Regeneration of β-cells might stop or reverse the progression of the disease. This Review discusses the different modelling systems and technologies currently used to study β-cell biology in health and disease.

Cachexia is a multi-organ syndrome associated with cancer. In this Review, Josep M. Argilés and colleagues discuss the role of different tissues and organs in cancer cachexia and examine studies that investigate the development of novel therapeutics for the condition.

The association between obesity and increased risk of developing cancer is partly driven by disruption of metabolism and inflammation in the adipose tissue. This Review discusses changes in the adipose tissue microenvironment during body-weight gain and how these changes affect tumour initiation and growth.

In a longitudinal study that tracked BMI from early life, most children with obesity at age 3 years had overweight or obesity by adolescence. Of adolescents with obesity, ~50% were affected by overweight or obesity from age 5 years onwards, and the most rapid increase in BMI had occurred between 2 and 6 years of age.

Therapeutic treatments that target multiple signalling pathways in obesity and type 2 diabetes mellitus (T2DM) could be more effective at reversing the progression of these diseases than current therapies. In this Review, the authors discuss advances in combination pharmacotherapies that target multiple pathways for the treatment of obesity and T2DM.

This Review focuses on the evolutionary origins, structure and signalling pathways of the Ca²⁺-sensing receptor (CaSR), as well as the roles of the CaSR in calcitropic and noncalcitropic diseases.

Evidence for the predictive value of IADPSG/WHO2013 diagnostic gestational diabetes mellitus criteria for long-term maternal and offspring outcomes is missing. Recently, William L Lowe Jr and colleagues report a high risk of maternal glycaemic disorders and childhood adiposity 10 to 14 years after untreated gestational diabetes mellitus in the HAPO Follow-up Study.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors prevent cardiovascular events by lowering levels of LDL cholesterol derived from the liver. However, PCSK9 is expressed in many other tissues, including the pancreas and central nervous system. This Review explores the functions of PCSK9 beyond the control of cholesterol levels.

Pituitary gigantism is a rare growth disorder caused by excessive release of growth hormone and insulin-like growth factor 1. This Review discusses the diagnosis, genetic causes and clinical management of pituitary gigantism.

The signalling events leading to insulin release from β-cells are tightly controlled and new techniques are needed to understand the complicated interactions. This Review discusses new optical tools available to further our understanding of β-cell function and insulin release.

Replacements for the chemical bisphenol A (BPA) have become commonplace in plastics labelled BPA free. However, many of these chemicals have similar structures and properties to BPA. A new study reports that replacement bisphenols, which were discovered as laboratory contaminants, are reproductive toxicants and that their effects might persist for multiple generations.

Over the past 10 years, evidence has accumulated to suggest that α-cells are involved in the development of diabetes mellitus. This Review outlines our current understanding of α-cells and discusses how they could be targeted in the treatment of diabetes mellitus.

This Review discusses the role of the Chinese Famine in the current epidemic of type 2 diabetes mellitus in China and highlights lessons to be learned.

Pharmacotherapy for obesity, as an adjunct to targeted behavioural modifications, can facilitate weight loss. Previous serotonergic candidates have been withdrawn owing to undesirable cardiovascular effects. A new study in a large sample of high-risk patients shows lorcaserin treatment leads to no greater increase in cardiovascular problems than placebo — what does this result mean for personalized pharmacotherapy for obesity?

Transplanting pancreatic islets in immune-isolating capsules might cure type 1 diabetes mellitus while avoiding the immunosuppression that is normally needed to protect transplanted islets from rejection. A recent study demonstrates that allogeneic islets can survive in capsules with improved biocompatibility without immunosuppression in non-human primates, bringing us one step closer to applying this therapy in humans.

This Review focuses on the function of hypoxia-inducible factors (HIFs) in controlling metabolism and their influence in metabolic diseases (including obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease). The therapeutic potential of targeting HIFs for the treatment of metabolic diseases will also be discussed.

Intravenous steroid therapy in thyroid eye disease has limitations and is potentially harmful at high doses. A steroid-sparing approach is a reasonable option, but combination therapy must be tested in randomized clinical trials designed to establish the efficacy and the potentially increased risk of adverse effects of combined immunosuppressive treatment.