Eur J Endocrinol
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DOI: 10.1530/eje.0.1330227
European Journal of Endocrinology, Vol 133, Issue 2, 227-234
Copyright © 1995 by European Society of Endocrinology
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Glucose induces calcium-dependent and calcium-independent insulin secretion from the pancreatic beta cell line MIN6

Nobuko Sakuma, San-e Ishikawa, Koji Okada, Jun-ichi Miyazaki and Toshikazu Saito

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 Ca2+-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 [Ca2+]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 [Ca2+]1 and insulin secretion disappeared. Also, L-leucine and L-arginine increased [Ca2+]1 and induced insulin secretion. Under Ca2+-free conditions, insulin release was still induced, without any change in [Ca2+]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 Ca2+. Cellular alkalinization occurred in response to all these stimulants, irrespective of the presence or absence of Ca2+. Forskolin, a diterpene activator of adenylate cyclase, produced insulin secretion independently of [Ca2+]1, which accompanied cellular alkalinization. Also, a high glucose level increased cellular cyclic AMP (cAMP) production in the presence and absence of Ca2+, and the effect was diminished by approximately 73% in Ca2+-free conditions. These results indicate that a high glucose level stimulates both Ca2+-dependent and -independent insulin secretion from pancreatic beta cells. We suggest that the cAMP production and the cellular alkalinization participate in the Ca2+-independent mechanism.

Nobuko Sakuma, Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji Minamikawachi-machi, Tochigi 329-04, Japan




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N. Itabashi, K. Okada, S. Muto, N. Fujita, T. Ohta, J.-i. Miyazaki, Y. Asano, and T. Saito
A Novel Enhancer of Insulinotrophic Action by High Glucose (JTT-608) Stimulates Insulin Secretion from Pancreatic beta -Cells via a New Cellular Mechanism
J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 953 - 960.
[Abstract] [Full Text]




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