Islet biology

This Review highlights mechanisms of glucagon secretion from pancreatic α-cells, including paracrine actions in islets and α-cell–β-cell crosstalk. Dysregulated glucagon secretion in metabolic diseases is also considered and the clinical potential of targeting glucagon is discussed.

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 examines the evidence that β-cells are active participants in the dialogue with the immune system during the development of type 1 diabetes mellitus. The authors suggest that therapies targeting β-cell health, vitality and function might prove essential, in combination with immunotherapy, to change the course of events leading to β-cell destruction.

This Review highlights the research advances, advantages and challenges in several different strategies for generating functional β-cells for therapeutic use in diabetes mellitus. In addition, scalable bioengineering processes are also discussed for the realization of the therapeutic potential of derived β-cells.

Understanding the mechanisms behind β-cell failure in diabetes mellitus is critical to prevent or revert disease. This Review highlights new findings from studies performed on human β-cells or on samples obtained from patients with type 1 or type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) has genetic and environmental risk factors that result in impaired glucose homeostasis. This Review discusses efforts to identify molecular mechanisms associated with T2DM susceptibility loci and highlights the current human models that are used to study β-cell development and function.

The dominant immune cell type causing pancreatic islet inflammation in individuals with obesity and/or type 2 diabetes mellitus is the macrophage. In this Review, we focus on the characteristics of inflammation in obese or type 2 diabetes mellitus islets and the consequences of this with respect to β-cell function.

In 2021, several discoveries shed light on the pathomechanisms of β-cell failure during the initiation and progression of diabetes mellitus, and validated novel molecular targets for intervention. Moreover, the field of stem-cell-derived replacements for β-cells is rapidly advancing. These advances bring us closer to therapies to protect and/or regenerate β-cell mass.

The development and application of effective immunotherapies for type 1 diabetes mellitus has lagged behind our ability to identify and stage individuals in pre-clinical stages of disease. This Year in Review addresses advances in immunotherapy aimed towards prevention and our readiness to roll out screening in the broader population.

A large fraction of patients with diabetes mellitus require insulin treatment to control glucose metabolism; however, this treatment brings risks of hypoglycaemia and provides suboptimal metabolic control. Transplantation of stem cell-derived pancreatic islet cells could be an ideal solution, which is approaching clinical translation.

Pancreatic islets, which are critical for glucose homeostasis, are endocrine microorgans embedded in the exocrine pancreas; their location has often limited studying their function. In 2019, advances in islet biology were achieved with new technologies extending findings from several decades ago and with conceptual advances built on findings from other fields.