Involvement of annexin-I in glucose-induced insulin secretion in rat pancreatic islets.
Annexin-I was demonstrated to specifically present in islets and not in exocrine tissues of the rat pancreas and to have a diffuse and homogeneous distribution in all islet cells in our previous study. In the present report, to clarify the functions of annexin-I in rat pancreatic islets, especially in beta-cells, we investigated the role of annexin-I in insulin secretion. Immunoelectron microscopic analysis of pancreatic beta-cells demonstrated that immunogold particles reactive to annexin-I were almost exclusively observed on most of the insulin-containing granules (approximately 90%) and less frequently located in cytosol and other organelles, such as the endoplasmic reticulum and mitochondria. The number of annexin-I gold particles located on insulin granules after oral glucose administration was significantly increased compared with that observed in fasted rats. Moreover, when the isolated islets were stimulated by a high concentration of glucose (20 mM), the phosphorylation of annexin-I was markedly enhanced, and it was synchronized to insulin secretion. This phosphorylation mainly occurred on serine residues. H-7 (100 microM), a potent inhibitor of protein kinase-C, inhibited the phosphorylation to about 90%. These findings suggest that annexin-I might be involved in the regulatory mechanism of glucose-induced insulin secretion in rat pancreatic islets via phosphorylation-dephosphorylation processes.
Ohnishi
M
M
Department of Internal Medicine, Kagawa Medical School, Japan.
Tokuda
M
M
Masaki
T
T
Fujimura
T
T
Tai
Y
Y
Itano
T
T
Matsui
H
H
Ishida
T
T
Konishi
R
R
Takahara
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D007546:Isoquinolines / Q000494:pharmacology; D016253:Microscopy, Immunoelectron; D015388:Organelles / Q000378:metabolism; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D017305:Annexin A1; D007328:Insulin; D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D005947:Glucose