Chronic Palmitate Exposure Inhibits Insulin Secretion by Dissociation of Ca2+ Channels from Secretory Granules

Hoppa, Michael B.; Collins, Stephan C.; Ramracheya, Reshma; Hodson, Leanne; Amisten, Stefan; Zhang, Quan; Johnson, P; Ashcroft, Frances M.; Rorsman, Patrik

doi:10.1016/j.cmet.2011.03.002

Cited by 38 publications

(86 citation statements)

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“…The submembrane compartment was distinguish from the general intracellular compartment in order to get a sufficiently rapid rise in the Ca 2+ -concentration after the onset of the depolarization. In this way, a behavior resembling TIRFM-imaging of [Ca 2+ ] mem (Hoppa et al, 2009) was obtained. The Ca 2+ -dynamics is described following (Chen et al, 2008;Pedersen and Sherman, 2009;Pedersen, 2010b), based on data from mouse β-cells (Chen et al, 2003).…”

Section: Exocytosis In Human β-Cellsmentioning

confidence: 93%

“…A variation of these models was recently (Pedersen, 2010b) used to study the effect of palmitate exposure on Ca 2+ and exocytosis (Hoppa et al, 2009). The question was whether palmitate disrupted Ca 2+ -channel clustering or, possibly in addition, moved granules away from Ca 2+ -channels.…”

Section: Mathematical Modeling Of Granule Dynamics In Rodent β-Cellsmentioning

confidence: 99%

“…The question was whether palmitate disrupted Ca 2+ -channel clustering or, possibly in addition, moved granules away from Ca 2+ -channels. Modeling simulations showed that no clear conclusion could be drawn from capacitance measurements alone, but it was argued that imaging data (Hoppa et al, 2009) favored the interpretation that palmitate exposure dissociated granules from Ca 2+ -channels.…”

Section: Mathematical Modeling Of Granule Dynamics In Rodent β-Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

Pedersen

Cortese

Eliasson

2011

Progress in Biophysics and Molecular Biology

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Section: Exocytosis In Human β-Cellsmentioning

confidence: 93%

Section: Mathematical Modeling Of Granule Dynamics In Rodent β-Cellsmentioning

confidence: 99%

Section: Mathematical Modeling Of Granule Dynamics In Rodent β-Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

Pedersen

Cortese

Eliasson

2011

Progress in Biophysics and Molecular Biology

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“…In addition to its crucial role in insulin exocytosis [45], [Ca 2+ ] i favours the maturation of proinsulin to insulin inside the granules extruded from the distal endoplasmic reticulum [46,47]. [Ca 2+ ] ER is also fundamental for processing enzymes implicated in the conversion of proinsulin to insulin (such as PC1/3 and PC2) and their inclusion inside the secretory granules.…”

Section: Discussionmentioning

confidence: 99%

The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion

et al. 2010

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Aims/hypothesis Suppressor of cytokine signalling (SOCS) proteins are powerful inhibitors of pathways involved in survival and function of pancreatic beta cells. Whereas SOCS1 and SOCS3 have been involved in immune and inflammatory processes, respectively, in beta cells, nothing is known about SOCS2 implication in the pancreas. Methods Transgenic (tg) mice were generated that constitutively produced SOCS2 in beta cells (βSOCS2) to define whether this protein is implicated in beta cell functioning and/or survival.Results Constitutive production of SOCS2 in beta cells leads to hyperglycaemia and glucose intolerance. This phenotype is not a consequence of decreased beta cell mass or inhibition of insulin synthesis. However, insulin secretion to various secretagogues is profoundly altered in intact animals and isolated islets. Interestingly, constitutive SOCS2 production dampens the rise in cytosolic free calcium concentration induced by glucose, while glucose metabolism is unchanged. Moreover, tg islets have a depletion in endoplasmic reticulum Ca 2+ stores, suggesting that SOCS2 interferes with calcium fluxes. Finally, inElectronic supplementary material The online version of this article

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“…In beta cells, blocking the K Vchannels leads to a prolongation of the action potentials and stimulation of insulin secretion [12,13] (but see [14]). …”

Section: Membrane Potential-regulated Potassium Channels In Alpha Cellsmentioning

confidence: 99%

The glucagon-producing alpha cell: an electrophysiologically exceptional cell

Braun

Rorsman

2010

Diabetologia

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Activation of potassium channels normally serves to reduce cellular activity but recent data indicate that the glucagon-secreting alpha cells are different in this respect and that inhibition of voltage-gated potassium channels results in a paradoxical inhibition of glucagon secretion. Here we discuss these findings and attempt to provide a model for the regulation of glucagon secretion that incorporates these observations.

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Chronic Palmitate Exposure Inhibits Insulin Secretion by Dissociation of Ca2+ Channels from Secretory Granules

Cited by 38 publications

References 0 publications

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans

The suppressor of cytokine signalling 2 (SOCS2) is a key repressor of insulin secretion

The glucagon-producing alpha cell: an electrophysiologically exceptional cell

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