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Temperature‐Sensitive Random Insulin Granule Diffusion is a Prerequisite for Recruiting Granules for Release
Author(s) -
Ivarsson Rosita,
Obermüller Stefanie,
Rutter Guy A.,
Galvanovskis Juris,
Renström Erik
Publication year - 2004
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2004.00216.x
Subject(s) - granule (geology) , exocytosis , insulin , biology , biophysics , microbiology and biotechnology , medicine , secretion , endocrinology , paleontology
Glucose‐evoked insulin secretion exhibits a biphasic time course and is associated with accelerated intracellular granule movement. We combined live confocal imaging of EGFP‐labelled insulin granules with capacitance measurements of exocytosis in clonal INS‐1 cells to explore the relation between distinct random and directed modes of insulin granule movement, as well as exocytotic capacity. Reducing the temperature from 34 °C to 24 °C caused a dramatic 81% drop in the frequency of directed events, but reduced directed velocities by a mere 25%. The much stronger temperature sensitivity of the frequency of directed events (estimated energy of activation ∼ 135 kJ/mol) than that of the granule velocities (∼ 22 kJ/mol) suggests that cooling‐induced suppression of insulin granule movement is attributable to factors other than reduced motor protein adenosine 5′‐triphosphatase activity. Indeed, cooling suppresses random granule diffusion by ∼ 50%. In the single cell, the number of directed events depends on the extent of granule diffusion. Finally, single‐cell exocytosis exhibits a biphasic pattern corresponding to that observed in vivo , and only the component reflecting 2nd phase insulin secretion is affected by cooling. We conclude that random diffusive movement is a prerequisite for directed insulin granule transport and for the recruitment of insulin granules released during 2nd phase insulin secretion.