Role of T-Type Ca2+ Channels in Basal Insulin Release

Li, Ming

doi:10.1007/978-3-7091-1413-1_10

Cited by 3 publications

(4 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increasing evidence indicates the pathological role of TCCs in the progression of different diseases [ 6 ]. It is crucial to develop selective TCC blockers to establish new treatments for these diseases.…”

Section: Discussionmentioning

confidence: 99%

“…As the only type of voltage-gated Ca 2+ channels that are activated at or near resting membrane potentials, T-type Ca 2+ channels (TCCs) play an important role in regulating [Ca 2+ ] i homeostasis in a variety of tissues, including pancreatic β-cells and tumor cells [ 1 , 2 , 3 , 4 ]. Therefore, TCC antagonists could be potentially useful for the treatment of chronic diseases associated with Ca 2+ dysregulation [ 5 , 6 , 7 ]. For this reason, it is imperative to develop more selective TCC antagonists for prospective clinical applications.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A New Computer Model for Evaluating the Selective Binding Affinity of Phenylalkylamines to T-Type Ca2+ Channels

2021

Pharmaceuticals

Self Cite

View full text Add to dashboard Cite

To establish a computer model for evaluating the binding affinity of phenylalkylamines (PAAs) to T-type Ca2+ channels (TCCs), we created new homology models for both TCCs and a L-type calcium channel (LCC). We found that PAAs have a high affinity for domains I and IV of TCCs and a low affinity for domains III and IV of the LCC. Therefore, they should be considered as favorable candidates for TCC blockers. The new homology models were validated with some commonly recognized TCC blockers that are well characterized. Additionally, examples of the TCC blockers created were also evaluated using these models.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A New Computer Model for Evaluating the Selective Binding Affinity of Phenylalkylamines to T-Type Ca2+ Channels

2021

Pharmaceuticals

Self Cite

View full text Add to dashboard Cite

show abstract

“…Others have also shown that the inhibition of T-type calcium channels reduced insulin secretion by 60–70% at 6 mM glucose in human pancreatic beta cells ( 46 ). Other authors have proposed that T-type Ca 2+ channels may increase the frequency of the spontaneous [Ca 2+ ]i spikes, resulting in premature release of insulin in non-stimulatory glucose conditions ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Calcium Channels in Postnatal Development of Rat Pancreatic Beta Cells and Their Role in Insulin Secretion

et al. 2018

View full text Add to dashboard Cite

Pancreatic beta cells during the first month of development acquire functional maturity, allowing them to respond to variations in extracellular glucose concentration by secreting insulin. Changes in ionic channel activity are important for this maturation. Within the voltage-gated calcium channels (VGCC), the most studied channels are high-voltage-activated (HVA), principally L-type; while low-voltage-activated (LVA) channels have been poorly studied in native beta cells. We analyzed the changes in the expression and activity of VGCC during the postnatal development in rat beta cells. We observed that the percentage of detection of T-type current increased with the stage of development. T-type calcium current density in adult cells was higher than in neonatal and P20 beta cells. Mean HVA current density also increased with age. Calcium current behavior in P20 beta cells was heterogeneous; almost half of the cells had HVA current densities higher than the adult cells, and this was independent of the presence of T-type current. We detected the presence of α1G, α1H, and α1I subunits of LVA channels at all ages. The Cav 3.1 subunit (α1G) was the most expressed. T-type channel blockers mibefradil and TTA-A2 significantly inhibited insulin secretion at 5.6 mM glucose, which suggests a physiological role for T-type channels at basal glucose conditions. Both, nifedipine and TTA-A2, drastically decreased the beta-cell subpopulation that secretes more insulin, in both basal and stimulating glucose conditions. We conclude that changes in expression and activity of VGCC during the development play an important role in physiological maturation of beta cells.

show abstract

“…Only the T type is a low-voltage gated channel. Without glucose stimulus, the Ttype of calcium channel on β-cells could be opened partially [32]. Functions of T-type calcium channel mediated hormone and neurotransmitter release under non-stimulus conditions have been intensely studied [33][34][35][36].…”

Section: Function Of T-type Calcium Channelsmentioning

confidence: 99%

View Insulin Resistance from an Interaction Between Pancreatic Islets and Peripheral Tissues

Li¹,

Lu²,

Wang³

2018

CMR

Self Cite

View full text Add to dashboard Cite

Curl rent hypotheses of insulin resistance mostly emphasize cellular mechanisms in peripheral tissues. Although received broad recognition, these opinions may have overlooked the interaction between pancreatic endocrine cells and the peripheral tissues in the process of establishment and maintenance of insulin resistance in the whole body. It has been suggested that basal hyperinsulinemia is the root cause of insulin resistance. Basal insulin release does not share the same intracellular mechanism of high glucose stimulated insulin release; instead, it is regulated by local Ca 2+ fluctuation and activation of the cAMP-Epac2/Rap1 signaling pathway. Basal insulin release is controlled by the interaction between pancreatic head β-cells and pancreatic tail α-cells, which release insulin and glucagon, respectively. In diabetes, an elevated basal insulin level would mitigate the sensitivity of peripheral tissues to insulin; the decreased insulin sensitivity and elevated plasma glucose concentration could further stimulate more basal insulin release partially by increasing T-type Ca 2+ channel expression and activity in β-cells. This interaction forms a positive feedback loop. Therefore, T-type Ca 2+ channel antagonists can potentially be employed to break this positive feedback loop, thus reversing insulin resistance.

show abstract

Role of T-Type Ca2+ Channels in Basal Insulin Release

Cited by 3 publications

References 61 publications

A New Computer Model for Evaluating the Selective Binding Affinity of Phenylalkylamines to T-Type Ca2+ Channels

A New Computer Model for Evaluating the Selective Binding Affinity of Phenylalkylamines to T-Type Ca2+ Channels

Calcium Channels in Postnatal Development of Rat Pancreatic Beta Cells and Their Role in Insulin Secretion

View Insulin Resistance from an Interaction Between Pancreatic Islets and Peripheral Tissues

Contact Info

Product

Resources

About