Insulin secretion from beta cells in intact mouse islets is targeted towards the vasculature

• Published in: Diabetologia Vol. 57; no. 8; pp. 1655 - 1663
• Main Authors: Low, Jiun T., Zavortink, Michael, Mitchell, Justin M., Gan, Wan J., Do, Oanh Hoang, Schwiening, Christof J., Gaisano, Herbert Y., Thorn, Peter
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2014; Springer; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exocytosis - drug effects; Exocytosis - physiology; Glucose; Glucose - pharmacology; Human Physiology; Hypotheses; Insulin; Insulin - metabolism; Insulin Secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Proteins; Synapses - drug effects; Synapses - metabolism; Synaptosomal-Associated Protein 25 - metabolism; Australia; United States > US; Synapse; Secretion; Beta cell; Islets; Exocytosis; Insulin; Vasculature; Endocrinopathy; Pancreatic hormone; Diabetes mellitus; Langerhans islet; Rodentia; Betacell; Vertebrata; Mammalia; Mouse; Animal; β Cell; Endocrine pancreas
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-014-3252-6

Aims/hypothesis
We set out to test the hypothesis that insulin secretion from beta cells is targeted towards the vasculature.
Methods
The spatial location of granule fusion was identified by live-cell two-photon imaging of mouse pancreatic beta cells within intact islets, using sulforhodamine B labelling. Three-dimensional (3D) immunofluorescence of pancreatic slices was used to identify the location of proteins associated with neuronal synapses.
Results
We demonstrated an asymmetric, non-random, distribution of sites of insulin granule fusion in response to glucose and focal targeting of insulin granule secretion to the beta cell membrane facing the vasculature. 3D immunofluorescence of islets showed that structural proteins, such as liprin, piccolo and Rab2-interacting molecule, normally associated with neuronal presynaptic targeting, were present in beta cells and enriched at the vascular face. In contrast, we found that syntaxin 1A and synaptosomal-associated protein 25 kDa (SNAP25) were relatively evenly distributed across the beta cells.
Conclusions/interpretation
Our results show that beta cells in situ, within intact islets, are polarised and target insulin secretion. This evidence for an ‘endocrine synapse’ has wide implications for our understanding of stimulus–secretion coupling in healthy islets and in disease.