Glucose Acutely Decreases pH of Secretory Granules in Mouse Pancreatic Islets

Stiernet, Patrick; Guiot, Yves; Gilon, Patrick; Henquin, Jean‐Claude

doi:10.1074/jbc.m513224200

Cited by 49 publications

(33 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results in no way indicate that adenine nucleotides are exclusive signals from high-glucose metabolism that govern second-phase insulin secretion (28). In the case of adenine nucleotides, we speculate their binding to granule K ATP channels might regulate priming of the granules to a calciumreleasable state by an ionic mechanism (5,45), stimulate trafficking to release sites, or enhance interactions there with exocytic and endocytic proteins (11,17,29,35). Further investigation of these regulatory pathways will be important to more fully understand the role of K ATP channels in the treatment of diabetic subjects (8,22,39,49).…”

Section: Discussionmentioning

confidence: 85%

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane K_ATPchannels

Geng¹,

Li²,

Bottino³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Drain P. Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane KATP channels. Am J Physiol Endocrinol Metab 293: E293-E301, 2007. First published April 3, 2007; doi:10.1152/ajpendo.00016.2007.-Understanding mechanisms by which glibenclamide stimulates insulin release is important, particularly given recent promising treatment by glibenclamide of permanent neonatal diabetic subjects. Antidiabetic sulfonylureas are thought to stimulate insulin secretion solely by inhibiting their high-affinity ATP-sensitive potassium (KATP) channel receptors at the plasma membrane of ␤-cells. This normally occurs during glucose stimulation, where ATP inhibition of plasmalemmal KATP channels leads to voltage activation of L-type calcium channels for rapidly switching on and off calcium influx, governing the duration of insulin secretion. However, growing evidence indicates that sulfonylureas, including glibenclamide, have additional KATP channel receptors within ␤-cells at insulin granules. We tested nonpermeabilized ␤-cells in mouse islets for glibenclamide-stimulated insulin secretion mediated by granule-localized KATP channels by using conditions that bypass glibenclamide action on plasmalemmal KATP channels. High-potassium stimulation evoked a sustained rise in ␤-cell calcium level but a transient rise in insulin secretion. With continued high-potassium depolarization, addition of glibenclamide dramatically enhanced insulin secretion without affecting calcium. These findings support the hypothesis that glibenclamide, or an increased ATP/ADP ratio, stimulates insulin secretion in part by binding at granule-localized KATP channels that functionally contribute to sustained second-phase insulin secretion.␤-cells; glibenclamide; permanent neonatal diabetes; exocytosis; endocytosis; adenosine 5Ј-triphosphate-sensitive potassium channels TO UNDERSTAND THE MECHANISMS underlying insulin secretion by glibenclamide, its functional sites of action in the ␤-cell of the endocrine pancreas must be identified. The plasmalemmal ATP-sensitive potassium (K ATP ) channel site for glibenclamide-stimulated insulin release is well studied (3). In glucose-stimulated insulin secretion (GSIS), the plasmalemmal K ATP channel transduces the signal of elevated glucose metabolism into calcium influx across the plasmalemma. The calcium then completes the final exocytic step by fusing previously primed insulin granules to the plasmalemma, experimentally observed as a transient first-phase insulin release (36).Generally, K ATP channels couple glucose metabolism and membrane electrical signaling (1, 2, 10, 16, 27). K ATP channels are ideal receptors for ligands signaling changes in glucose metabolism, because they are designed as sensors of adenine nucleotide levels. ATP binding to the K ir 6.2 subunit of the K ATP channel inhibits the potassium efflux that otherwise maintains the electrically negative resting state of the cell. ADP binding to the sulfonylurea receptor 1 (SUR1) subunit of the K ATP channel can antagonize the in...

show abstract

Section: Discussionmentioning

confidence: 85%

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane K_ATPchannels

Geng¹,

Li²,

Bottino³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…We evaluated the effects of acidic organelles disturbing agents on the insulin secretion induced by 12 mmol/l glucose or GLP-1 signaling molecules. Bafilomycin A1 and concanamycin A, inhibitors of vacuolar H ϩ -ATPase, have been reported to inhibit glucose-induced insulin secretion by mouse islets (35). The glucose-induced insulin secretions were not affected by GPN or bafilomycin A1 (Fig.…”

Section: Preparation Of Islets Pancreatic Islets Were Isolated From mentioning

confidence: 85%

Generation of Nicotinic Acid Adenine Dinucleotide Phosphate and Cyclic ADP-Ribose by Glucagon-Like Peptide-1 Evokes Ca2+ Signal That Is Essential for Insulin Secretion in Mouse Pancreatic Islets

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Glucagon-like peptide-1 (GLP-1) increases intracellular Ca 2ϩ concentrations ([Ca 2ϩ ] i ), resulting in insulin secretion from pancreatic ␤-cells. The molecular mechanism(s) of the GLP-1-mediated regulation of [Ca 2ϩ ] i was investigated. 2ϩ ] i were measured in ␤-cells isolated from Cd38 ϩ/ϩ and Cd38 Ϫ/Ϫ mice. Calcium-mobilizing second messengers were identified by measuring levels of nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic ADP-ribose (ADPR), using a cyclic enzymatic assay. To locate NAADP-and cyclic ADPRproducing enzyme(s), cellular organelles were separated using the sucrose gradient method. [Ca 2ϩ ] i increase showed a cooperative Ca 2ϩ signal, i.e., an initial [Ca 2ϩ ] i rise mediated by the action of NAADP that was produced in acidic organelles and a subsequent long-lasting increase of [Ca 2ϩ ] i by the action of cyclic ADPR that was produced in plasma membranes and secretory granules. GLP-1 sequentially stimulated production of NAADP and cyclic ADPR in the organelles through protein kinase A and cAMP-regulated guanine nucleotide exchange factor II. Furthermore, the results showed that NAADP production from acidic organelles governed overall Ca 2ϩ signals, including insulin secretion by GLP-1, and that in addition to CD38, enzymes capable of synthesizing NAADP and/or cyclic ADPR were present in ␤-cells. These observations were supported by the study with Cd38 Ϫ/Ϫ ␤-cells, demonstrating production of NAADP, cyclic ADPR, and Ca 2ϩ signal with normal insulin secretion stimulated by GLP-1. RESEARCH DESIGN AND METHODS-GLP-1-induced changes in [Ca RESULTS-A GLP-1-induced CONCLUSIONS-Our

show abstract

“…Glucose induces changes in ␤-cell cytosolic pH (pH c ), the mechanisms and role of which in stimulus-secretion coupling are still debated. Except for two studies reporting no effect of glucose on pH c in mouse ␤-cells (11) or an acidification in rat islets (12), there is a large consensus that high glucose increases pH c in mouse islets (13)(14)(15)(16)(17), rat islets (18,19) and insulin-secreting cell lines (20,21). In contrast, there is no agreement on the mechanisms implicated in this alkalinization.…”

mentioning

confidence: 84%

Glucose-induced Cytosolic pH Changes in β-Cells and Insulin Secretion Are Not Causally Related

Stiernet¹,

Nenquin²,

Moulin³

et al. 2007

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The contribution of Na ؉ /H ؉ exchange (achieved by NHE proteins) to the regulation of ␤-cell cytosolic pH c , and the role of pH c changes in glucose-induced insulin secretion are disputed and were examined here. Using real-time PCR, we identified plasmalemmal NHE1 and intracellular NHE7 as the two most abundant NHE isoforms in mouse islets. We, therefore, compared insulin secretion, cytosolic free Ca

show abstract

Glucose Acutely Decreases pH of Secretory Granules in Mouse Pancreatic Islets

Cited by 49 publications

References 58 publications

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane K_ATPchannels

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane K_ATPchannels

Generation of Nicotinic Acid Adenine Dinucleotide Phosphate and Cyclic ADP-Ribose by Glucagon-Like Peptide-1 Evokes Ca2+ Signal That Is Essential for Insulin Secretion in Mouse Pancreatic Islets

Glucose-induced Cytosolic pH Changes in β-Cells and Insulin Secretion Are Not Causally Related

Contact Info

Product

Resources

About

Glucose Acutely Decreases pH of Secretory Granules in Mouse Pancreatic Islets

Cited by 49 publications

References 58 publications

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane KATPchannels

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane KATPchannels

Generation of Nicotinic Acid Adenine Dinucleotide Phosphate and Cyclic ADP-Ribose by Glucagon-Like Peptide-1 Evokes Ca2+ Signal That Is Essential for Insulin Secretion in Mouse Pancreatic Islets

Glucose-induced Cytosolic pH Changes in β-Cells and Insulin Secretion Are Not Causally Related

Contact Info

Product

Resources

About

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane K_ATPchannels

Antidiabetic sulfonylurea stimulates insulin secretion independently of plasma membrane K_ATPchannels