Action potentials and insulin secretion: new insights into the role of Kv channels

Jacobson, David A.; Philipson, Louis H.

doi:10.1111/j.1463-1326.2007.00784.x

Cited by 46 publications

(46 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kv2.1-null mice, present increased insulin secretion that results in lower fasting glucose levels or hypoglycemia compared with wild-type mice (44). Electrophysiological experiments using isolated ␤-cells show that Kv currents are extremely reduced compared with the wild-type, indicating that Kv2.1 is the major component of Kv channels in mouse ␤-cells.…”

Section: Returning To Resting Potentialmentioning

confidence: 98%

“…All types of pancreatic ␤-cells studied to date (rodent, dog, and human) as well as several cell lines (INS-1, HIT-T15, RINm5F, ␤TC3, MIN6) express a number of these channels where three types have been described; canonical (TRPC1, -4, -6), melastatin-like TRPM (TRPM2, -4, -5), and vanilloid-receptor-like TRPV (TRPV1), and it is thought that some of these TRP channels could provide a depolarizing background cationic current (44).…”

Section: Transient Receptor Potential Type Channels In ␤-Cells As Canmentioning

confidence: 99%

See 1 more Smart Citation

Channel regulation of glucose sensing in the pancreatic β-cell

Hiriart¹,

Aguilar‐Bryan²

2008

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Mammalian ␤-cells are acutely and chronically regulated by sensing surrounding glucose levels that determine the rate at which insulin is secreted, to maintain euglycemia. Experimental research in vitro and in vivo has shown that, when these cells are exposed to adverse conditions like long periods of hypoglycemia or hyperglycemia, their capability to sense glucose is decreased. Understanding the normal physiology and identifying the main players along this route becomes paramount. In this review, we have taken on the task of looking at the role that ion channels play in the regulation of this process, delineating the different families, and describing the signaling that parallels the glucose sensing process that results in insulin release. transient receptor potential; sodium current; calcium current; insulin secretion; insulin secretion coupling PANCREATIC ␤-CELLS secrete insulin in response to a "sensing" mechanism triggered by an increase in extracellular glucose from basal levels. Stimulation-secretion coupling in ␤-cells is different from other cell types because instead of being mediated by receptor binding, glucose needs to be transported into the cytoplasm and metabolized to stimulate exocytosis. Previous reviews (76, 51) have divided the glucose-sensing apparatus into proximal metabolic and distal ionic apparatus. The proximal component includes glucose transport through a specific transporter on the ␤-cell membrane (GLUT1 for humans, GLUT2 for rodents) followed by the glycolytic pathway, which results in an increase in the ATP/ADP ratio that triggers the distal component comprising a cascade of electrochemical events that culminate in an increase in intracellular calcium ([Ca 2ϩ ] i ) and stimulation of insulin secretion. This process can be augmented by several enteroinsular hormones [glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and CCK] and neurotransmitters like acetylcholine, which amplify the secretory response through the activation of adenylate cyclase or phospholipase C.During fasting, basal glucose levels are ϳ5-6 mM, and the ␤-cell membrane is polarized at resting potential. Dean and Matthews (17,18), almost four decades ago, were the first to show that when glucose rises voltage across the membrane oscillates, generating electrical activity leading to an increase in [Ca 2ϩ ] i and subsequent insulin secretion. This activity consists of an initial slow membrane depolarization, followed by a fast depolarization and subsequent plateau level on which bursts of action potentials are superimposed to finally repolarize the plasma membrane, which returns to its initial polarized state at resting potential. This oscillating process regenerates as long as the glucose concentration is elevated and results from the activity of ion channels localized to the ␤-cell plasma membrane. Insulin is an anabolic hormone, essential for the maintenance of glucose homeostasis, because, among other effects, insulin increases glucose uptake in many cell types to promote nu...

show abstract

Section: Returning To Resting Potentialmentioning

confidence: 98%

Section: Transient Receptor Potential Type Channels In ␤-Cells As Canmentioning

confidence: 99%

Channel regulation of glucose sensing in the pancreatic β-cell

Hiriart¹,

Aguilar‐Bryan²

2008

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…1A and have been reviewed extensively (13,21,22,27,42,55,62). The main points can be summarized as follows.…”

Section: The Secretory Mechanismmentioning

confidence: 99%

Signal integration at the level of ion channel and exocytotic function in pancreatic β-cells

MacDonald

2011

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Glucose-stimulated insulin secretion occurs as a consequence of Ca 2ϩ influx through voltage-gated calcium channels following membrane depolarization. The ␤-cell membrane potential is under the control of a constellation of ion channels and transporters (1)(2)(3). A key player that couples glucose stimulation to membrane depolarization is the ATP-sensitive potassium (K ATP ) channel (4 -6).…”

mentioning

confidence: 99%

“…Abnormal gating or expression of the channel in the ␤-cell membrane that results in a gain or a loss of channel function is now well recognized to underlie neonatal diabetes or congenital hyperinsulinism, respectively (7). The recovery of ␤-cell membrane potential to a resting hyperpolarized state is due to outward potassium currents carried largely by the voltage-gated delayed rectifier potassium channel Kv2.1 (1,3,8,9). Pharmacological inhibition or genetic ablation of Kv2.1 results in prolonged glucose-evoked action potential duration in ␤-cells, elevated serum insulin, and increased glucose tolerance (10).…”

mentioning

confidence: 99%