The insulin secretory granule as a signaling hub.
The insulin granule was previously thought of as merely a container, but accumulating evidence suggests that it also acts as a signaling node. Regulatory pathways intersect at but also originate from the insulin granule membrane. Examples include the small G-proteins Rab3a and Rab27a, which influence granule movement, and the transmembrane proteins (tyrosine phosphatase receptors type N) PTPRN and PTPRN2, which upregulate β-cell transcription and proliferation. In addition, many cosecreted compounds possess regulatory functions, often related to energy metabolism. For instance, ATP and γ-amino butyric acid (GABA) modulate insulin and glucagon secretion, respectively; C-peptide protects β-cells and kidney cells; and amylin reduces gastric emptying and food intake via the brain. In this paper, we review the current knowledge of the insulin granule proteome and discuss its regulatory functions.
Suckale
Jakob
J
Molecular Diabetology, Paul Langerhans Institute Dresden, School of Medicine and University Clinic Carl Gustav Carus, Dresden University of Technology, Dresden 01307, Germany.
Solimena
Michele
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002864:Chromogranins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D002864:Chromogranins; D007328:Insulin; D000255:Adenosine Triphosphate; D020559:Monomeric GTP-Binding Proteins