Acute Stimulation with Long Chain Acyl-CoA Enhances Exocytosis in Insulin-secreting Cells (HIT T-15 and NMRI β-Cells)

Deeney, Jude T.; Gromada, Jesper; Høy, Marianne; Olsen, Henrik Baare; Rhodes, Christopher J.; Prentki, Marc; Berggren, Per Olof; Corkey, Barbara E.

doi:10.1074/jbc.275.13.9363

Cited by 160 publications

(120 citation statements)

References 55 publications

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“…We therefore explored the possibility that a decrease in the level of phosphorylation of ACC at Ser-79, and hence an increase in cellular malonyl-CoA synthesis, may prompt the release of insulin through a Ca# + -independent mechanism involving an increase in cellular acyl-CoA concentration, as described previously in permeabilized HIT-T15 cells [70]. However, arguing against this model, the decreased phosphorylation of ACC elicited by AMPK DN (Figure 8D) failed to lead to any increase in intracellular [malonyl-CoA] at either low or high glucose concentrations ( Figure 9B).…”

Section: Figure 10 Possible Roles Of Ampk In the Control Of Insulin Rmentioning

confidence: 99%

Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression

Xavier

Leclerc

Váradi

et al. 2003

Biochemical Journal

246

239

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AMP-activated protein kinase (AMPK) has recently been implicated in the control of preproinsulin gene expression in pancreatic islet β-cells [da Silva Xavier, Leclerc, Salt, Doiron, Hardie, Kahn and Rutter (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 4023–4028]. Using pharmacological and molecular strategies to regulate AMPK activity in rat islets and clonal MIN6 β-cells, we show here that the effects of AMPK are exerted largely upstream of insulin release. Thus forced increases in AMPK activity achieved pharmacologically with 5-amino-4-imidazolecarboxamide riboside (AICAR), or by adenoviral overexpression of a truncated, constitutively active form of the enzyme (AMPKα1.T172D), blocked glucose-stimulated insulin secretion. In MIN6 cells, activation of AMPK suppressed glucose metabolism, as assessed by changes in total, cytosolic or mitochondrial [ATP] and NAD(P)H, and reduced increases in intracellular [Ca2+] caused by either glucose or tolbutamide. By contrast, inactivation of AMPK by expression of a dominant-negative form of the enzyme mutated in the catalytic site (AMPKα1.D157A) did not affect glucose-stimulated increases in [ATP], NAD(P)H or intracellular [Ca2+], but led to the unregulated release of insulin. These results indicate that inhibition of AMPK by glucose is essential for the activation of insulin secretion by the sugar, and may contribute to the transcriptional stimulation of the preproinsulin gene. Modulation of AMPK activity in the β-cell may thus represent a novel therapeutic strategy for the treatment of type 2 diabetes mellitus.

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Section: Figure 10 Possible Roles Of Ampk In the Control Of Insulin Rmentioning

confidence: 99%

Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression

Xavier

Leclerc

Váradi

et al. 2003

Biochemical Journal

246

239

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“…LC-CoA seems to facilitate the fusion of secretory granules with the b-cell plasma membrane, promoting the insulin release. Thus, the exocytosis of insulin in the b-cell might be regulated through an increased fusion of granules to the plasma membrane and subsequent increase of the available docking sites where granules in the reserve pool can be bound (Deeney et al, 2000).…”

Section: Fa Metabolism In B-cellsmentioning

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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“…Streptolysin-O-Analysis of insulin secretion stimulated by direct Ca 2ϩ influx after cell permeabilization with streptolysin-O was performed as described previously (24,25). Briefly, cells co-cultured for 24 h were washed with KRB buffer containing 2.75 mM glucose, equilibrated in this solution for 45 min, and then permeabilized using 3.2 units/ml streptolysin-O (Sigma) for 30 min on ice as described previously (24,26).…”

Section: Methodsmentioning

confidence: 99%

Transcellular Neuroligin-2 Interactions Enhance Insulin Secretion and Are Integral to Pancreatic β Cell Function

Suckow

Zhang

Egodage

et al. 2012

Journal of Biological Chemistry

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Background:The synaptic protein neuroligin-2 is present on the pancreatic ␤ cell surface and affects insulin secretion. Results: Insulin secretion increases when ␤ cells contact adjacent cells expressing neuroligin; soluble neuroligin inhibits secretion. Conclusion: Clustered neuroligin-2 enhances insulin secretion in a transcellular manner, likely by promoting secretory microdomain formation. Significance: Transcellular protein-protein interactions paralleling the transsynaptic interactions that drive synapse formation may guide ␤ cell functional maturation.

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Acute Stimulation with Long Chain Acyl-CoA Enhances Exocytosis in Insulin-secreting Cells (HIT T-15 and NMRI β-Cells)

Cited by 160 publications

References 55 publications

Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression

Role for AMP-activated protein kinase in glucose-stimulated insulin secretion and preproinsulin gene expression

Pleiotropic effects of fatty acids on pancreatic β‐cells

Transcellular Neuroligin-2 Interactions Enhance Insulin Secretion and Are Integral to Pancreatic β Cell Function

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