Reversible Ca2+-dependent Translocation of Protein Kinase C and Glucose-induced Insulin Release

Deeney, Jude T.; Cunningham, Barbara A.; Chheda, Shefali; Bokvist, Krister; Juntti‐Berggren, Lisa; Lam, Kenny; Korchak, Helen M.; Corkey, Barbara E.; Berggren, Per‐Olof

doi:10.1074/jbc.271.30.18154

Cited by 48 publications

(30 citation statements)

References 36 publications

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“…Arguing against the possibility that this behavior reflects a nonspecific coagulation of GFP molecules on the membrane, such hot spots are rarely observed using phospholipid-dependent membrane-targeted EGFP chimeras that incorporate pleckstrin homology domains using either confocal (50) or TIRF microscopy. 2 The present data are also consistent with the findings of Yedovitzky et al Interestingly, we failed to find any change in the localization of either PKC␦ or PKC in response to glucose or other secretagogue stimuli (Fig. 7).…”

Section: Discussionsupporting

confidence: 83%

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Dynamics of Glucose-induced Membrane Recruitment of Protein Kinase C βII in Living Pancreatic Islet β-Cells

Pinton¹,

Tsuboi²,

Ainscow³

et al. 2002

Journal of Biological Chemistry

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The mechanisms by which glucose may affect protein kinase C (PKC) activity in the pancreatic islet ␤-cell are presently unclear. By developing adenovirally expressed chimeras encoding fusion proteins between green fluorescent protein and conventional (␤II), novel (␦), or atypical () PKCs, we show that glucose selectively alters the subcellular localization of these enzymes dynamically in primary islet and MIN6 ␤-cells.

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Section: Discussionsupporting

confidence: 83%

“…Biochemical studies of the activation of PKC are complicated by the need for cell disruption and isolation of membrane and cytosol fractions (2) or for cell fixation and immunocytochemistry (2)(3)(4). Each of these approaches is limited by the difficulty of detecting any changes in subcellular localization, which are spatially or temporally complex.…”

mentioning

confidence: 99%

Dynamics of Glucose-induced Membrane Recruitment of Protein Kinase C βII in Living Pancreatic Islet β-Cells

Pinton¹,

Tsuboi²,

Ainscow³

et al. 2002

Journal of Biological Chemistry

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“…Increased DAG and Ca 2þ lead to insulin secretion mediated by PKC that interact with components of the microtubular/exocytotic machinery (Turk et al, 1987;Deeney et al, 1996) (Fig. 1).…”

Section: Effect Of Ffa On Pkcmentioning

confidence: 99%

Pleiotropic effects of fatty acids on pancreatic β‐cells

Haber

Ximenes

Procópio

et al. 2002

Journal Cellular Physiology

148

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Hyperlipidemia is frequently associated with insulin resistance states as found in type 2 diabetes and obesity. Effects of free fatty acids (FFA) on pancreatic b-cells have long been recognized. Acute exposure of the pancreatic b-cell to FFA results in an increase of insulin release, whereas a chronic exposure results in desensitization and suppression of secretion. We recently showed that palmitate augments insulin release in the presence of non-stimulatory concentrations of glucose. Reduction of plasma FFA levels in fasted rats or humans severely impairs glucose-induced insulin release. These results imply that physiological plasma levels of FFA are important for b-cell function. Although, it has been accepted that fatty acid oxidation is necessary for its stimulation of insulin secretion, the possible mechanisms by which fatty acids (FA) affect insulin secretion are discussed in this review. Long-chain acylCoA (LC-CoA) controls several aspects of the b-cell function including activation of certain types of protein kinase C (PKC), modulation of ion channels, protein acylation, ceramide-and/or nitric oxide (NO)-mediated apoptosis, and binding to nuclear transcriptional factors. The present review also describes the possible effects of FA on insulin signaling. We showed for the first time that acute exposure of islets to palmitate upregulates the intracellular insulin-signaling pathway in pancreatic islets. Another aspect considered in this review is the source of FA for pancreatic islets. In addition to be exported to the medium, lipids can be transferred from leukocytes (macrophages) to pancreatic islets in co-culture. This process consists an additional source of FA that may plays a significant role to regulate insulin secretion.

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“…1B). Nonetheless, this does not preclude the possibility that normal levels of these (25,27,42) as well as other PKCs, such as cPKC-␤II and nPKC-␦ (26,43,44), may also serve as DAG receptors capable of being activated, undergo cellular translocation, and exert additional and independent priming actions on insulin exocytosis. More studies performed on these mice islets will be required to see if these PKCs act either sequentially to Munc13-1 or in parallel, perhaps in a manner capable of bypassing the Munc13-1 deficiency.…”

Section: H567kmentioning

confidence: 99%

Munc13-1 Deficiency Reduces Insulin Secretion and Causes Abnormal Glucose Tolerance

et al. 2006

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Munc13-1 is a diacylglycerol (DAG) receptor that is essential for synaptic vesicle priming. We recently showed that Munc13-1 is expressed in rodent and human islet ␤-cells and that its levels are reduced in islets of type 2 diabetic humans and rat models, suggesting that Munc13-1 deficiency contributes to the abnormal insulin secretion in diabetes. To unequivocally demonstrate the role of Munc13-1 in insulin secretion, we studied heterozygous Munc13-1 knockout mice (؉/؊), which exhibited elevated glucose levels during intraperitoneal glucose tolerance tests with corresponding lower serum insulin levels. Munc13-1؉/؊ mice exhibited normal insulin tolerance, indicating that a primary islet ␤-cell secretory defect is the major cause of their hyperglycemia. Consistently, glucosestimulated insulin secretion was reduced 50% in isolated Munc13-1 ؉/؊ islets and was only partially rescued by phorbol ester potentiation. The corresponding alterations were minor in mice expressing one allele of a Munc13-1 mutant variant, which does not bind DAG (H567K/؉). Capacitance measurements of Munc13-1 ؉/؊ and Munc13-1 H567k/؉ islet ␤-cells revealed defects in granule priming, including the initial size and refilling of the releasable pools, which become accentuated by phorbol ester potentiation. We conclude that Munc13-1 plays an important role in glucosestimulated insulin secretion and that Munc13-1 deficiency in the pancreatic islets as occurs in diabetes can reduce insulin secretion sufficient to cause abnormal glucose homeostasis. Diabetes 55: [1421][1422][1423][1424][1425][1426][1427][1428][1429] 2006 N ormal glucose-stimulated insulin secretion (GSIS) from pancreatic islets follows a biphasic pattern (1). The first phase is a robust release lasting ϳ5-10 min and is triggered by ATPsensitive K ϩ channel-dependent Ca 2ϩ entry into the pancreatic ␤-cells. This is followed by a second phase and sustained release, which is regulated by second messengers including diacyglycerol (DAG), cAMP, and permissive elevated levels of Ca 2ϩ (2). In patients with type 2 diabetes, this pattern of secretion is perturbed, resulting in an abolished first phase and a blunted second phase (2). It is generally accepted that the biphasic secretion pattern is contributed by the release of spatially and functionally distinct insulin granules. The morphologically docked granule pool at the plasma membrane contains Ͻ10% of the total of Ͼ10,000 insulin granules per cell, and only a fraction (20 -30%) of the docked pool is primed and fusion competent for immediate release (3). It is the release of this docked and primed granule pool that contributes to the first phase of insulin secretion (2-4). One of the aims of the present study was to identify the proteins that prime insulin granules for release.As in neurons (5), exocytosis in pancreatic islet ␤-cells is regulated by the SNARE (soluble N-ethylmaleimidesensitive factor attachment protein [SNAP] receptor) proteins VAMP, SNAP-25, and syntaxin-1A (6). These SNARE proteins form a ternary complex capable of ...

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Reversible Ca2+-dependent Translocation of Protein Kinase C and Glucose-induced Insulin Release

Cited by 48 publications

References 36 publications

Dynamics of Glucose-induced Membrane Recruitment of Protein Kinase C βII in Living Pancreatic Islet β-Cells

Dynamics of Glucose-induced Membrane Recruitment of Protein Kinase C βII in Living Pancreatic Islet β-Cells

Pleiotropic effects of fatty acids on pancreatic β‐cells

Munc13-1 Deficiency Reduces Insulin Secretion and Causes Abnormal Glucose Tolerance

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