Commentary: ATP: The crucial component of secretory vesicles: Accelerated ATP/insulin exocytosis and prediabetes

Duvoor, Chitharanjan; Dendi, Vijaya Sena; Marco, Asween; Shekhawat, Nawal S.; Chada, Aditya; Ravilla, Rahul; Musham, Chaitanya K.; Mirza, Wasique; Chaudhury, Arun

doi:10.3389/fphys.2017.00053

Cited by 2 publications

(2 citation statements)

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“…Amperometry reports the soluble insulin in the cell vicinity, although the peptide is stored by the β-cell in the crystalline form40. Intravesicular solubilisation of insulin would substantially increase the osmotic pressure41, hence the hormone is expected to be secreted in its crystalline form. We therefore believe that the delay reflects the time needed for the dissolution of insulin crystals (>7 min in blood plasma42).…”

Section: Resultsmentioning

confidence: 99%

Monitoring real-time hormone release kinetics via high-content 3-D imaging of compensatory endocytosis

et al. 2018

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High-content real-time imaging of hormone secretion in tissues or cell populations is a challenging task, which is unlikely to be resolved directly, despite immense translational value. We approach this problem indirectly, using compensatory endocytosis, a process that closely follows exocytosis in the cell, as a surrogate read-out for secretion. The tissue is immobilized in an open-air perifusion chamber and imaged using a two-photon microscope. A fluorescent polar tracer, perifused through the experimental circuit, gets trapped into the cells via endocytosis, and is quantified using a feature-detection algorithm. The signal of the tracer that accumulates into the endocytotic system reliably reflects stimulated exocytosis, which is demonstrated via co-imaging of the latter using existing reporters. A high signal-to-noise ratio and compatibility with multisensor imaging affords the real-time quantification of the secretion at the tissue/population level, whereas the cumulative nature of the signal allows imprinting of the "secretory history" within each cell. The technology works for several cell types, reflects disease progression and can be used for human tissue.

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Section: Resultsmentioning

confidence: 99%

Monitoring real-time hormone release kinetics via high-content 3-D imaging of compensatory endocytosis

et al. 2018

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“…However, it has been reported that ATP levels (indicative of overall intracellular energy supply) remain constant beyond the extracellular glucose concentration of 10 mM in human, rat, and mouse islet cells. , This phenomenon could potentially impose an additional metabolic load on cells during heightened insulin secretion. Further, it is interesting to note that ATP also plays a crucial role in the acidification of insulin-carrying vesicles and insulin exocytosis, , in addition to its general role as the currency of intracellular energy. Thus, there is an obvious limit to intracellular energy generation, independent of the availability of metabolic energy sources, such as glucose, beyond a certain amount.…”

Section: Introductionmentioning

confidence: 99%

Secretory Conservation in Insulin Producing Cells: Is There a System-Level Law of Mass Action in Biology?

Firdos,

Mittal

2023

ACS Omega

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Altered secretion of insulin from pancreatic β-cells can manifest into disorders. For example, a lack of endogenously produced and/or secreted insulin results in Type 1 diabetes (and other associated subtypes). Pancreatic βcells are the endocrine secretory cells that promote insulin secretion in response to glucose stimulation. Secretion in response to extracellular triggers is an interplay among various signaling pathways, transcription factors, and molecular mechanisms. The Mouse Insulinoma 6 (MIN6) cell line serves as a model system for gaining mechanistic insights into pancreatic β-cell functions. It is obvious that higher glucose consumption and increased insulin secretion are correlated. However, it has been reported that intracellular ATP levels remain ∼ constant beyond the extracellular glucose (EG) concentration of 10 mM. Therefore, any cause−effect relationship between glucose consumption (GC) and enhanced insulin secretion (eIS) remains unclear. We also found that total cellular protein, as well as total protein content in the culture "supernatant," remains constant regardless of varying EG concentrations. This indicated that eIS may be at the cost of (a) intracellular synthesis of other proteins and (b) secretion of other secretory proteins, or both (a) and (b), somehow coupled with GC by cells. To gain insights into the above, we carried out a transcriptome study of MIN6 cells exposed to hypoglycemic (HoG = 2.8 mM EG) and hyperglycemic (HyG = 25 mM EG) conditions. Expression of transcripts was analyzed in terms of Fragments Per Kilobase of transcript per Million mapped reads and Transcripts Per Million (FPKM and TPM) as well as values obtained by normalizing w.r.t. "∑(FPKM)" and "∑(TPM)." We report that HyG extracellular conditions lead to an ∼2-fold increase in insulin secretion compared to HoG measured by the enzyme-linked immunosorbent assay (ELISA) and transcripts of secreted proteins as well as their isoforms decreased in HyG conditions compared to HoG. Our results show for the first time that eIS in HyG conditions is at the cost of reduced transcription of other secreted proteins and is coupled with higher GC. The higher GC at increased extracellular glucose also indicates a yet undiscovered role of glucose molecules enhancing insulin secretion, since ATP levels resulting from glucose metabolism have been reported to be constant above an EG concentration of 10 mM. While extrapolation of our results to clinical implications is ambitious at best, this work reports novel cellular level aspects that seem relevant in some clinical observations pertaining to Type 1 diabetes. In addition, the conservatory nature of cellular secretions in insulin-secreting cells, discovered here, may be a general feature in cell biology.

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Commentary: ATP: The crucial component of secretory vesicles: Accelerated ATP/insulin exocytosis and prediabetes

Cited by 2 publications

References 54 publications

Monitoring real-time hormone release kinetics via high-content 3-D imaging of compensatory endocytosis

Monitoring real-time hormone release kinetics via high-content 3-D imaging of compensatory endocytosis

Secretory Conservation in Insulin Producing Cells: Is There a System-Level Law of Mass Action in Biology?

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