Insulin secretion is mediated by pancreatic β-cells that are able to sense glucose levels in the blood. This involves glucose-induced activation of glycolysis, which in turn stimulates mitochondrial ATP synthesis, leading to a Ca2+ influx into the cell that then triggers insulin exocytosis. However, the exact role of Ca2+ in the process has been debated. On page 1929, Umberto De Marchi and co-workers therefore set out to clarify whether Ca2+ signalling and mitochondrial activation are a prerequisite for insulin secretion. To that end, they compare the effects of glucose and the mitochondrial substrate methylsuccinate to investigate the coupling between metabolism and secretion in insulinoma β-cells (INS-1E), which secrete insulin. Although both substrates induced insulin secretion, the underlying mechanisms are distinct, in that methylsuccinate failed to induce a significant rise in intracellular Ca2+ and insulin exocytosis proceeded independently of mitochondrial ATP synthesis. However, in the case of both substrates, Ca2+ was nevertheless required for exocytosis, as the addition of diazoxide, which prevents Ca2+ influx, inhibited secretion. Taken together, this work presents evidence for a new pathway downstream of mitochondrial activation that only requires a small increase in intracellular Ca2+ to mediate insulin secretion; this might also be important in pathological contexts such as type 2 diabetes.
A new mechanism coupling mitochondria activation to insulin secretion Free
A new mechanism coupling mitochondria activation to insulin secretion. J Cell Sci 1 June 2017; 130 (11): e1103. doi:
Download citation file:
Advertisement
Cited by
JCS fast-track option

Have a paper that has been reviewed elsewhere? JCS is pleased to consider such manuscripts for fast-tracked decision making. Send us your manuscript together with the full set of reviews and decision letters, and we will make an initial decision within one week.
Special Issue – Cell Biology of Mitochondria

Our special issue on ‘Cell Biology of Mitochondria’ is now complete. Explore this issue and read the Editorial from our Guest Editors Ana J. García-Sáez and Heidi McBride.
Save the date – Imaging Cell Dynamics

We are delighted to announce that we will be hosting a 2026 Imaging Cell Dynamics meeting. This meeting will provide a unique opportunity to bring together experts working at the interface between cell biology and imaging. Save the date for 11-14 May 2026 and register for more information.
Origin and evolution of mitochondrial inner membrane composition

In this Review, Kailash Venkatraman and colleagues provide an examination of the morphological similarities between prokaryotic intracytoplasmic membranes and mitochondrial inner membranes, and whether cristae evolution has driven specialisation of the mitochondrial lipidome.
Resolution in super-resolution microscopy
Super-resolution microscopy (SRM) has emerged as a powerful tool for biological discovery. In this Perspective, Kirti Prakash and colleagues compile expert opinions on crucial, yet often overlooked, aspects of SRM that are essential for maximising its benefits and advancing the field.