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Glucose induces calcium-dependent and calcium-independent insulin secretion from the pancreatic beta cell line MIN6

1995; Oxford University Press; Volume: 133; Issue: 2 Linguagem: Inglês

10.1530/eje.0.1330227

1479-683X

Nobuko Sakuma, San‐e Ishikawa, Koji Okada, Jun‐ichi Miyazaki, T. Saito,

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Sakuma N, Ishikawa S, Okada K, Miyazaki J, Saito T, Glucose induces calcium-dependent and calcium-independent insulin secretion from the pancreatic beta cell line MIN6. Eur J Endocrinol 1995;133:227–34. ISSN 0804–4643 The present study was undertaken to determine whether there are Ca 2+ -dependent and -independent pathways of glucose-induced insulin secretion from the pancreatic beta cell line MIN6. Glucose at a concentration of 16.7 mmol/l caused marked increases in cellular free calcium [Ca 2+ ] 1 ) and insulin secretion, which depended on glucose metabolism. When cells were pretreated with 20 mmol/l mannoheptulose, an inhibitor of glucokinase, the 16.7 mmol/l glucose induced a rise in [Ca 2+ ] 1 and insulin secretion disappeared. Also, l -leucine and l -arginine increased [Ca 2+ ] 1 and induced insulin secretion. Under Ca 2+ -free conditions, insulin release was still induced, without any change in [Ca 2+ ] 1 , by these three different stimulants. The cumulative values of insulin secretion were 13.7–29.3% of the control, which were significantly less than that in the presence of Ca 2+ . Cellular alkalinization occurred in response to all these stimulants, irrespective of the presence or absence of Ca 2+ . Forskolin, a diterpene activator of adenylate cyclase, produced insulin secretion independently of [Ca 2+ ] 1 , which accompanied cellular alkalinization. Also, a high glucose level increased cellular cyclic AMP (cAMP) production in the presence and absence of Ca 2+ , and the effect was diminished by approximately 73% in Ca 2+ -free conditions. These results indicate that a high glucose level stimulates both Ca 2+ -dependent and -independent insulin secretion from pancreatic beta cells. We suggest that the cAMP production and the cellular alkalinization participate in the Ca 2+ -independent mechanism. Nobuko Sakuma, Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji Minamikawachi-machi, Tochigi 329-04, Japan