Glucose-regulated pulsatile insulin release from mouse islets via the K(ATP) channel-independent pathway

Westerlund, Johanna; Ortsäter, Henrik; Palm, Fredrik; Sundsten, Tea; Bergsten, Peter

doi:10.1530/eje.0.1440667

Cited by 6 publications

(2 citation statements)

References 51 publications

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“…oscillations of either metabolism or Ca 2 + , may promote pulsatile insulin secretion independently, but can act synergistically if attributed to pancreatic islets in parallel [42]. To specifically support the findings of the present study it should be mentioned that a diazoxide-derived constitutive opening of the K ATP -channel in pancreatic islets was unable to abolish pulsatile secretion ex vivo [43]. While our previous data suggest that glycolytic oscillations are essential for pulsatile insulin secretion in humans [28], the findings of the present study indicate that an impairment of ATP-synthesis is insufficient to abolish insulin secretory oscillations in humans.…”

Section: Discussionsupporting

confidence: 72%

Regular Insulin Secretory Oscillations Despite Impaired ATP Synthesis in Friedreich Ataxia Patients

Meyer¹,

Carlqvist²,

Vorgerd³

et al. 2006

Horm Metab Res

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Friedreich Ataxia is an inherited disorder caused by decreased expression of a mitochondrial protein called frataxin. Deficiency of this protein causes reduced biogenesis of iron-sulfur clusters, and subsequently impaired synthesis and replenishment of ATP IN VIVO. Basal secretion of insulin occurs in an oscillating manner presumably triggered by ATP-dependent feedback inhibition of glycolytic flux. Hence, individuals with reduced ATP synthesis rates should possibly exhibit impaired insulin secretory oscillations if these were solely dependent on ATP. In the present study Friedreich Ataxia patients with a presumptive impairment of ATP synthesis in pancreatic beta-cells were evaluated for regularity of basal secretory oscillations of insulin. Healthy siblings were employed as controls. In conflict with the initial hypothesis, no differences in regards to oscillation patterns were observed between patients and controls. Supported by EX VIVO evidence, these findings tentatively suggest that pulsatile insulin secretion might not be exclusively dependent on ATP feedback inhibition in humans.

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Section: Discussionsupporting

confidence: 72%

Regular Insulin Secretory Oscillations Despite Impaired ATP Synthesis in Friedreich Ataxia Patients

Meyer¹,

Carlqvist²,

Vorgerd³

et al. 2006

Horm Metab Res

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“…This experiment was repeated with 3 islets and all responded in a similar manner. The fluo-4 response observed using the microfluidic perfusion system was similar to those obtained with a conventional perfusion system [22], indicating that the system developed will be suitable for future studies on islets of Langerhans or other cell types.…”

Section: Resultsmentioning

confidence: 70%

Microfluidic multi-analyte gradient generator

et al. 2010

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A microfluidic device was developed to produce temporal concentration gradients of multiple analytes. Four on-chip pumps delivered pulses of three analytes and buffer to a 14 cm channel where the pulses were mixed to homogeneity. The final concentration of each analyte was dependent on the temporal density of the pulses from each pump. The concentration of each analyte was varied by changing the number of pump cycles from each reservoir while maintaining the total number of pump cycles per unit time to ensure a constant total flow rate in the device. To gauge the independent nature of each pump, sinusoidal waves of fluorescein concentration were produced from each pump with independent frequencies and amplitudes. The resulting fluorescence intensity was compared to a theoretical summation of the waves and the experimental data matched the theoretical waves within 1%, indicating that the pumps were operating independently and outputting the correct frequency and amplitude. The device was used to demonstrate the role of ATP-sensitive K+ channels in glucose-stimulated increases in intracellular [Ca2+] in islets of Langerhans. Perfusion of single islets of Langerhans with combinations of glucose, diazoxide, and K+ resulted in intracellular Ca2+ patterns similar to what has been observed using conventional perfusion devices. The system will be useful in other studies with islets of Langerhans, as well as other assays that require the modulation of multiple analytes in time.

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KATP Channel-Independent Pathway and the Glucoreceptor

Aizawa

Komatsu

2018

Glucose-Sensing Receptor in Pancreatic Beta-Cells

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Glucose-regulated pulsatile insulin release from mouse islets via the K(ATP) channel-independent pathway

Cited by 6 publications

References 51 publications

Regular Insulin Secretory Oscillations Despite Impaired ATP Synthesis in Friedreich Ataxia Patients

Regular Insulin Secretory Oscillations Despite Impaired ATP Synthesis in Friedreich Ataxia Patients

Microfluidic multi-analyte gradient generator

KATP Channel-Independent Pathway and the Glucoreceptor

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