Work

Mitochondrial movement in pancreatic alpha cells requires Miro2 and is regulated by glucose

Year: 2025

Type: article

Abstract: Under normal physiological conditions, glucagon is released from pancreatic alpha cells to elevate circulating glucose levels in response to hypoglycemia. In patients with type 2 diabetes, glucagon secretion is dysregulated, but the underlying mechanisms remain unclear. Several hypotheses have been suggested to explain the coupling of blood glucose sensing to electrical activity and glucagon secretion from alpha cells. Here, we show that glucose rapidly regulates mitochondrial motility and localization in alpha cells. Under conditions of low glucose, mitochondria are arrested in positions further from the nucleus, correlating with increased ATP/ADP in the sub-plasma membrane space. We also find that knockdown (KD) of Mitochondrial Rho GTPase 2 (Miro2), but not Miro1, reduces mitochondrial motility in alpha cells and impairs glucose-induced inhibition of glucagon secretion without effects on insulin secretion or mitochondrial motility in non-alpha islet cells. These findings highlight the significance of mitochondrial motility for alpha cell function and reveal fundamental differences between alpha and beta cells.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.110984

Authors: Maia H. Ekstrand, Sameena Nawaz, Anne Clark, Benoit Hastoy, Jakob G. Knudsen

Institutions: University of Copenhagen, Churchill Hospital, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism

Language: English

Topic: Pancreatic function and diabetes

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,430