Calmodulin and pancreatic B-cell function

Valverde, Isabel; Malaisse, Willy

doi:10.1007/bf01971452

Cited by 20 publications

(8 citation statements)

References 41 publications

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“…Taken together, these findings demonstrate that the usual complement of ion channels are present in the CaM beta cell and are functional. While there is some evidence that CaM-regulated pathways may modulate ion channels in beta cells (24,25), the 5-fold overexpression of CaM in these beta cells (1) appears to have no direct effects on the ion channels.…”

Section: Discussionmentioning

confidence: 99%

Defective Glycolysis and Calcium Signaling Underlie Impaired Insulin Secretion in a Transgenic Mouse

Ribar

Jan

Augustine

et al. 1995

Journal of Biological Chemistry

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] i transients to near normal levels. Electrophysiological analysis of the beta cell ion channels revealed that Ca 2؉ currents, delayed rectifier K ؉ currents, and K ؉ ATP channel currents were similar in transgenic and nontransgenic cells, suggesting that these ion channels were able to function normally. However, whereas K ؉ ATP channel currents in control cells were reduced by 50% by the presence of high glucose, those in transgenic cells were unaltered. Addition of tolbutamide inhibited this channel and enhanced the secretion of insulin in response to glucose for both control and transgenic cells. As these observations implicated a metabolic defect, glucose utilization, which is an indicator of glucose metabolism and ATP production in beta cells, was measured and found to be reduced by 40% in the transgenic cells. These data support the contention that excessive levels of calmodulin may compromise the ability of the beta cell to metabolize glucose and to modulate the state of the K ؉ ATP channel, resulting in an inadequate control of the membrane potential, which collectively impair [Ca 2؉ ] i and thus insulin secretion in response to glucose.

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Section: Discussionmentioning

confidence: 99%

Defective Glycolysis and Calcium Signaling Underlie Impaired Insulin Secretion in a Transgenic Mouse

Ribar

Jan

Augustine

et al. 1995

Journal of Biological Chemistry

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“…If this were true for the voltage-dependent Ca 2ϩ channels of beta-cells, then CaM-8 may interfere with the binding of Ca 2ϩ /CaM to these channels. However, currently there is no evidence that either CaM-8 or CaM participate in modulating this channel through a direct binding mechanism (10,40).…”

Section: Discussionmentioning

confidence: 99%

“…One of the original aims in developing mouse lines which overexpress CaM and CaM-8 was to explore the role of CaM in cell growth and differentiated cellular function (10,44,45) in the pancreatic beta-cell. Initial analysis of these transgenic mice suggested that CaM might be part of the glucose-regulated signaling pathway that triggers the exocytotic secretion of insulin (11,12,15).…”

Section: Discussionmentioning

confidence: 99%

Alterations in Calcium Channel Currents Underlie Defective Insulin Secretion in a Transgenic Mouse

Jan

Ribar

Means

et al. 1996

Journal of Biological Chemistry

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“…These effects of calcium are probably mediated by calcium-binding proteins, some of which may also serve as calcium buffers. Thus, islets of Langerhans contain calcium-binding proteins, such as calmodulin, as well as calcium-dependent protein kinases, such as calcium/calmodulin-dependent protein kinase or protein kinase-C (Sugden et al 1979;Gagliardino et al 1980;Tanigawa et al 1982;Valverde and Malaisse 1984;Easom et al 1990;Watkins 1991). Protein phosphorylation is thought to be essential for full activation of the secretory machinery in insulinproducing B-cells (Ämmälä et al 1994;Ribar et al 1995).…”

Section: Introductionmentioning

confidence: 96%

Rodent pancreatic islet cells contain the calcium-binding proteins calcineurin and calretinin

Redecker

Cetin

1997

Histochemistry and Cell Biology

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Calcium is known to be of critical importance for hormone secretion in the insulin-producing B-cells of the endocrine, pancreas. Calcium-mediated intracellular signal transduction and the regulation of the concentration of free calcium in B-cells probably involve calcium-binding proteins. In the present study, we have investigated the expression of the calcium/calmodulin-dependent phosphatase, calcineurin, and the EF-hand calcium-binding protein, calretinin, in pancreata of hamsters, gerbils, and rats by immunocytochemistry. Immunocytochemical investigations of serial semithin sections of plastic-embedded pancreata revealed that calcineurin and calretinin were constantly present in islet cells of all three species. In addition to B-cells, these proteins could also be detected in glucagon (A-), somatostatin (D-), and pancreatic polypeptide (PP-) cells. Non-B-cells, especially glucagon-producing A-cells, often exhibited a significantly higher degree of immunoreactivity for both calcium-binding proteins than B-cells. Thus, calcineurin and calretinin may play distinct roles in the regulation of calcium-dependent secretory activities of the different pancreatic endocrine cell types.

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Calmodulin and pancreatic B-cell function

Cited by 20 publications

References 41 publications

Defective Glycolysis and Calcium Signaling Underlie Impaired Insulin Secretion in a Transgenic Mouse

Defective Glycolysis and Calcium Signaling Underlie Impaired Insulin Secretion in a Transgenic Mouse

Alterations in Calcium Channel Currents Underlie Defective Insulin Secretion in a Transgenic Mouse

Rodent pancreatic islet cells contain the calcium-binding proteins calcineurin and calretinin

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