TALK-1 and TALK-2 channels in pancreatic β-cell function
Abstract
Diabetes is a major non-communicable disease in which impaired insulin secretion contributes to loss of glucose homeostasis. ATP-sensitive K+ (KATP) channels couple glucose metabolism to β-cell electrical activity and are established therapeutic targets. However, KATP-dependent depolarization alone does not fully explain the regulation of insulin secretion. Emerging evidence identifies the two-pore-domain K+ channels TALK-1 and TALK-2 as additional regulators of β-cell function. This Mini Review integrates genetic, mechanistic, and pharmacological evidence to examine how TALK channels regulate β-cell function and to distinguish established cellular effects from unresolved implications for diabetes. TALK-1 studies link membrane excitability, endoplasmic reticulum (ER) Ca2+ homeostasis, and mitochondrial function to secretory regulation, while disease-associated variants support its relevance to diabetes. Recent human islet experiments show that TALK-2 regulates ER Ca2+ handling and modulates basal insulin release and the secretory response to glucose. Together, these findings indicate that the secretory consequences of TALK channel modulation depend on glucose availability and metabolic context. Selective TALK-1 inhibitors provide tools to test mechanisms previously investigated mainly through genetic manipulation. Key unresolved questions concern the relative contributions of plasma membrane and ER channels, the effects of sustained inhibition, and consequences for other islet hormones. We discuss how addressing these questions can establish whether TALK channel modulation improves glucose-responsive insulin secretion and preserves islet function, and whether these effects translate into sustained improvements in glucose homeostasis in vivo.
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BibTeX
@article{prayoga2026talk1,
title = {{TALK-1 and TALK-2 channels in pancreatic β-cell function}},
author = {Anjas Happy Prayoga and Dawon Kang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.2015446},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.2015446},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TALK-1 and TALK-2 channels in pancreatic β-cell function
AU - Anjas Happy Prayoga
AU - Dawon Kang
PY - 2026
DA - 2026/10/30
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.2015446
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.2015446
AB - Diabetes is a major non-communicable disease in which impaired insulin secretion contributes to loss of glucose homeostasis. ATP-sensitive K+ (KATP) channels couple glucose metabolism to β-cell electrical activity and are established therapeutic targets. However, KATP-dependent depolarization alone does not fully explain the regulation of insulin secretion. Emerging evidence identifies the two-pore-domain K+ channels TALK-1 and TALK-2 as additional regulators of β-cell function. This Mini Review integrates genetic, mechanistic, and pharmacological evidence to examine how TALK channels regulate β-cell function and to distinguish established cellular effects from unresolved implications for diabetes. TALK-1 studies link membrane excitability, endoplasmic reticulum (ER) Ca2+ homeostasis, and mitochondrial function to secretory regulation, while disease-associated variants support its relevance to diabetes. Recent human islet experiments show that TALK-2 regulates ER Ca2+ handling and modulates basal insulin release and the secretory response to glucose. Together, these findings indicate that the secretory consequences of TALK channel modulation depend on glucose availability and metabolic context. Selective TALK-1 inhibitors provide tools to test mechanisms previously investigated mainly through genetic manipulation. Key unresolved questions concern the relative contributions of plasma membrane and ER channels, the effects of sustained inhibition, and consequences for other islet hormones. We discuss how addressing these questions can establish whether TALK channel modulation improves glucose-responsive insulin secretion and preserves islet function, and whether these effects translate into sustained improvements in glucose homeostasis in vivo.
SN - 1663-9812
ER -