The digitonin-permeabilized pancreatic islet model. Effect of <i>myo</i>-inositol 1,4,5-trisphosphate on Ca2+ mobilization

Wolf, Bryan A.; Comens, P G; Ackermann, Karen; Sherman, William R.; McDaniel, Michael L.

doi:10.1042/bj2270965

Cited by 64 publications

(36 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the mechanism of the defect is reduced expression of IP 3 receptors. It has long been known that activation of IP 3 receptors causes calcium release from intracellular stores in the pancreatic ␤ cell (26,27). Although IP 3 receptor-mediated calcium release is clearly involved in muscarinic potentiation of insulin secretion, the role of these receptors in glucose-induced secretion remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca ²⁺ signaling, and insulin secretion in the anx 7(+/−) knockout mouse

Srivastava

Atwater

Glasman

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

123

118

View full text Add to dashboard Cite

The mammalian anx7 gene codes for a Ca 2؉ -activated GTPase, which supports Ca 2؉ ͞GTP-dependent secretion events and Ca 2؉ channel activities in vitro and in vivo. To test whether anx7 might be involved in Ca 2؉ signaling in secreting pancreatic ␤ cells, we knocked out the anx7 gene in the mouse and tested the insulinsecretory properties of the ␤ cells. The nullizygous anx7 (؊͞؊) phenotype is lethal at embryonic day 10 because of cerebral hemorrhage. However, the heterozygous anx7 (؉͞؊) mouse, although expressing only low levels of ANX7 protein, is viable and fertile. The anx7 (؉͞؊) phenotype is associated with a substantial defect in insulin secretion, although the insulin content of the islets, is 8-to 10-fold higher in the mutants than in the normal littermate control. We infer from electrophysiological studies that both glucose-stimulated secretion and voltage-dependent Ca 2؉ channel functions are normal. However, electrooptical recordings indicate that the (؉͞؊) mutation has caused a change in the ability of inositol 1,4,5-trisphosphate (IP3)-generating agonists to release intracellular calcium. The principle molecular consequence of lower anx7 expression is a profound reduction in IP3 receptor expression and function in pancreatic islets. The profound increase in islets, ␤ cell number, and size may be a means of compensating for less efficient insulin secretion by individual defective pancreatic ␤ cells. This is a direct demonstration of a connection between glucoseactivated insulin secretion and Ca 2؉ signaling through IP3-sensitive Ca 2؉ stores.

show abstract

Section: Discussionmentioning

confidence: 99%

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca ²⁺ signaling, and insulin secretion in the anx 7(+/−) knockout mouse

Srivastava

Atwater

Glasman

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

123

118

View full text Add to dashboard Cite

show abstract

“…On the day of experiment, they were washed once with KRB without glucose and Ca 2ϩ and washed once with TES buffer (50 mM TES, 100 mM KCl, 2 mM MgCl 2 , 1 mM ATP, 0.1% BSA, 3 mM glucose, 1 mM EGTA, pH 7.40). Cells were incubated for 15 min with 0.5 ml of TES buffer containing digitonin as described previously (33,44). In another set of experiments, cells were washed once with KRB and once with KG buffer (140 mM potassium glutamate, 5 mM ATP, 5 mM NaCl, 7 mM MgSO 4 , 0.4 mM EGTA, 1% BSA, and 20 mM HEPES, pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

Synaptotagmin III/VII Isoforms Mediate Ca2+-induced Insulin Secretion in Pancreatic Islet β-Cells

Gao¹,

Reavey‐Cantwell²,

Young

et al. 2000

Journal of Biological Chemistry

104

124

View full text Add to dashboard Cite

Synaptotagmins (Syt) play important roles in Ca2؉ -induced neuroexocytosis. Insulin secretion of the pancreatic ␤-cell is dependent on an increase in intracellular Ca 2؉ ; however, Syt involvement in insulin exocytosis is poorly understood. Reverse transcriptase-polymerase chain reaction studies showed the presence of Syt isoforms III, IV, V, and VII in rat pancreatic islets, whereas Syt isoforms I, II, III, IV, V, VII, and VIII were present in insulin-secreting ␤TC3 cell. Syt III and VII proteins were identified in rat islets and ␤TC3 and RINm5F ␤-cells by immunoblotting. Confocal microscopy showed that Syt III and VII co-localized with insulin-containing secretory granules. Two-fold overexpression of Syt III in RINm5F ␤-cell (Syt III cell) was achieved by stable transfection, which conferred greater Ca 2؉ sensitivity for exocytosis, and resulted in increased insulin secretion. Glyceraldehyde ؉ carbachol-induced insulin secretion in Syt III cells was 2.5-fold higher than control empty vector cells, whereas potassium-induced secretion was 6-fold higher. In permeabilized Syt III cells, Ca 2؉ -induced and mastoparan-induced insulin secretion was also increased. In Syt VII-overexpressing RINm5F ␤-cells, there was amplification of carbachol-induced insulin secretion in intact cells and of Ca 2؉ -induced and mastoparan-induced insulin secretion in permeabilized cells. In conclusion, Syt III/VII are located in insulincontaining secretory granules, and we suggest that Syt III/VII may be the Ca 2؉ sensor or one of the Ca 2؉ sensors for insulin exocytosis of the ␤-cell.Insulin exocytosis from the ␤-cell of the islets of Langerhans is stimulated by various physiological secretagogues that include glucose, amino acids, and receptor-mediated agonists such as acetylcholine, cholecystokinin, and glucagon like-peptide 1 (1-7). A common mechanism of action for these secretagogues is to cause an increase in cytosolic Ca 2ϩ . Elevation of intracellular Ca 2ϩ is due to an influx of extracellular Ca 2ϩ through voltage-dependent L-type Ca 2ϩ channel and/or mobilization of intracellular Ca 2ϩ from the endoplasmic reticulum (8 -17). However, the mechanisms by which Ca 2ϩ induces insulin granule fusion with the plasma membrane of ␤-cell remain unclear (1,16,18,20,21).1 is a family of membrane proteins initially found to be expressed in brain. At the present, 11 members of Syt have been identified (22,23). The Syt molecule has a single transmembrane domain and two Ca 2ϩ regulatory C 2 domains. The C 2 domains mediate Ca 2ϩ -dependent and Ca 2ϩ -independent interactions with target molecules that may regulate membrane fusion and membrane budding reactions (24,25). Literature concerning the expression and functions of Syt in pancreatic ␤-cell is very limited and contradictory. In an earlier study (26), Syt was found in the non-␤-cell of the islet mantle, but not in the ␤-cell, using a non-isoform-specific antibody, and the mRNAs of Syt A and B were absent in mouse pancreatic ␤-cell and RINm5F cells as demonstrated by in situ hybridization...

show abstract

“…Western Blot Analysis of Cytosolic Cytochrome c-To avoid mitochondrial contamination, extraction of cytosol was accomplished by permeabilization of the islet plasma membrane (30,31). Islets were incubated in 24-well plates (500/well) containing 500 l of Krebs-Ringer bicarbonate under various conditions.…”

Section: Imaging and Quantification Of Cytosolic Ca 2ϩmentioning

confidence: 99%

Control of Insulin Secretion by Cytochrome c and Calcium Signaling in Islets with Impaired Metabolism

Rountree

Neal

Lisowski

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Intracellular calcium and metabolic signals mediate glucose-induced insulin secretion. Results: In metabolically compromised islets, calcium signaling was robust, whereas reduction and translocation of cytochrome c were diminished. Conclusion: Data are consistent with a rate-determining role at the level of cytochrome c for insulin secretion. Significance: Impairment of metabolic control preferentially affects cytochrome c versus calcium signaling.

show abstract

The digitonin-permeabilized pancreatic islet model. Effect of myo-inositol 1,4,5-trisphosphate on Ca2+ mobilization

Cited by 64 publications

References 31 publications

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca ²⁺ signaling, and insulin secretion in the anx 7(+/−) knockout mouse

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca ²⁺ signaling, and insulin secretion in the anx 7(+/−) knockout mouse

Synaptotagmin III/VII Isoforms Mediate Ca2+-induced Insulin Secretion in Pancreatic Islet β-Cells

Control of Insulin Secretion by Cytochrome c and Calcium Signaling in Islets with Impaired Metabolism

Contact Info

Product

Resources

About

The digitonin-permeabilized pancreatic islet model. Effect of myo-inositol 1,4,5-trisphosphate on Ca2+ mobilization

Cited by 64 publications

References 31 publications

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca 2+ signaling, and insulin secretion in the anx 7(+/−) knockout mouse

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca 2+ signaling, and insulin secretion in the anx 7(+/−) knockout mouse

Synaptotagmin III/VII Isoforms Mediate Ca2+-induced Insulin Secretion in Pancreatic Islet β-Cells

Control of Insulin Secretion by Cytochrome c and Calcium Signaling in Islets with Impaired Metabolism

Contact Info

Product

Resources

About

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca ²⁺ signaling, and insulin secretion in the anx 7(+/−) knockout mouse

Defects in inositol 1,4,5-trisphosphate receptor expression, Ca ²⁺ signaling, and insulin secretion in the anx 7(+/−) knockout mouse