Join us at the Keystone Symposia on Islet Biology and Diabetes: Beta Cell Compensation, Failure and Recovery, March 2026, in Breckenridge, with field leaders!

Neither country has been able to stop continuous spread of the highly contagious virus within the past year.

Mitochondrial dysfunction and declining energy production are hallmarks of aging, yet we lack a comprehensive systems-level view of ATP synthase (Comp…

Nature Reviews Endocrinology, Published online: 22 October 2025; doi:10.1038/s41574-025-01201-0Fusion with blood vessel organoids supports pancreatic islet function

Some doctoral programmes are admitting no students at all amid uncertainty about federal science funding.

Mitophagy is a crucial quality control process that preserves metabolic efficiency by selectively targeting damaged mitochondria for removal. Given the high metabolic demand of pancreatic β cells’ insulin secretion, disruption of mitophagy contributes to the mitochondrial dysfunction and β cell failure that are a common feature of both type 1 and type 2 diabetes (T1D and T2D). We review the impact of mitophagy on β cell responses to (patho)physiologic stressors that underlie the development of T1D and T2D. We examine how β cells engage mitophagy in the adaptive response to metabolic, inflammatory, and oxidative damage. We also dissect the importance of ubiquitin- and receptor-mediated mitophagy, methodological advances to quantify mitophagy in β cells, and ongoing efforts to pharmacologically target mitophagy to preserve β cell health and improve glycemic control.

Charcot-Marie-Tooth disease type 2A (CMT2A) is the most common axonal CMT and is associated with an early onset and severe motor-dominant phenotype. CMT2A is mainly caused by dominant mutations in the...

TRAF6 bridges innate immune signaling to mitophagy to promote glucose control during metabolic stress.

Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as...

TRAF6 bridges innate immune signaling to mitophagy to promote glucose control during metabolic stress.

Aims/hypothesis Pancreatic ductal adenocarcinoma-related diabetes mellitus (PDAC-DM) is a paraneoplastic syndrome with a poorly understood pathophysiology. PDAC-DM is often clinically confused with type 2 diabetes, resulting in delayed cancer detection and poorly individualised hyperglycaemia treatment. We investigated whether these forms of diabetes can be distinguished at the metabolic level. Methods Adults with either cancer treatment-naive PDAC-DM (n=28) or type 2 diabetes (n=97), and with diabetes onset within 3 years, underwent mixed-meal tolerance tests to investigate glucose metabolism. Outcomes included insulin sensitivity (Matsuda index), insulin secretion (insulinogenic index), beta cell function (oral disposition index), insulin clearance, and postprandial glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) responses. Results Compared with type 2 diabetes, individuals with PDAC-DM showed ~2.5-fold greater insulin sensitivity, ~81% lower insulin secretion and ~40% lower beta cell function. Insulin clearance was higher in the PDAC-DM group than the type 2 diabetes group, with and without adjustment for insulin sensitivity. Glucagon and GLP-1 levels increased after a meal in both groups, but levels were higher in the PDAC-DM group. GIP levels were similar between groups. The metabolic differences between groups persisted after adjustment for age, sex and BMI. Conclusions/interpretation PDAC-DM and type 2 diabetes are metabolically distinct, with different defects responsible for hyperglycaemia. PDAC-DM is characterised predominantly by insulin deficiency and displays higher insulin sensitivity than type 2 diabetes. There are also differences in alpha cell regulation and insulin clearance compared with type 2 diabetes. These findings identify biological characteristics that may have implications for individualised treatment of PDAC-DM and guide diagnostic biomarker discovery for early PDAC diagnosis. Graphical Abstract

α cells can generate and secrete both glucagon and GLP-1 with distinct processing enzymes to control metabolism.