Modulation of hepatocellular swelling-activated K<sup>+</sup> currents by phosphoinositide pathway-dependent protein kinase C

Wang, Penny Y.T.; Hill, Ceredwyn E.

doi:10.1152/ajpcell.00602.2005

Cited by 21 publications

(37 citation statements)

References 50 publications

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“…KCNQ1 expression was demonstrated in liver (12,25,26), skeletal muscle (15), and several epithelia, including kidney (11, 17, 22, 34, 47, Ϫ/Ϫ and kcnq1 ϩ/ϩ mice. Arithmetic means Ϯ SE (n ϭ 7-9 each group) of plasma glucose concentrations following intraperitoneal injection of 0.15 U/kg body wt insulin in kcnq1 Ϫ/Ϫ (F) and kcnq1 ϩ/ϩ (E) mice.…”

Section: Discussionmentioning

confidence: 99%

“…To study the cellular K ϩ uptake, livers of 14-to 20-wk-old male and female mice with a body weight of [22][23][24][25][26][27][28] For the determination of the glucose tolerance, mice were fasted overnight and glucose (3 g/kg body wt) was injected intraperitoneally. A drop of blood was then drawn via the tail vein and read by a glucometer (Accutrend; Roche, Mannheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…The observations indicate that KCNQ1 is a novel molecule affecting insulin sensitivity of glucose metabolism. K ϩ channels; blood glucose; kidney; liver; skeletal muscle THE PORE-FORMING K ϩ CHANNEL ␣-subunit KCNQ1 (KvLQT1) is expressed in the heart (6,41) and skeletal muscle (15) and in several epithelial tissues, including the stria vascularis (55), the renal proximal tubule (51), gastric parietal cells (11,17,22), intestine (11,22,34,47,49,51), and liver (12,25,26).…”

mentioning

confidence: 99%

“…KCNQ1 further participates in cell volume regulation (3,18,25,26,53). In turn, cell volume has been shown to be a critical element in the regulation of metabolism and signaling of insulin (19 -21, 44).…”

mentioning

confidence: 99%

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Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

Boini

Graf²,

Hennige³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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The pore-forming K+-channel α-subunit KCNQ1 is expressed in a wide variety of tissues including heart, skeletal muscle, liver, and epithelia. Most recent evidence revealed an association of the KCNQ1 gene with the susceptibility to type 2 diabetes. KCNQ1 participates in the regulation of cell volume, which is, in turn, critically important for the regulation of metabolism by insulin. The present study explored the influence of KCNQ1 on insulin-induced cellular K+ uptake and glucose metabolism. Insulin (100 nM)-induced K+ uptake was determined in isolated perfused livers from KCNQ1-deficient mice ( kcnq1−/−) and their wild-type littermates ( kcnq1+/+). Moreover, plasma glucose and insulin levels, intraperitoneal glucose (3 g/kg) tolerance, insulin (0.15 U/kg)-induced hypoglycemia, and peripheral uptake of radiolabeled 3H-deoxy-glucose were determined in both genotypes. Insulin-stimulated hepatocellular K+ uptake was significantly more sustained in isolated perfused livers from kcnq1−/− mice than from kcnq1+/+mice. The decline of plasma glucose concentration following an intraperitoneal injection of insulin was again significantly more sustained in kcnq1−/− than in kcnq1+/+ mice. Both fasted and nonfasted plasma glucose and insulin concentrations were significantly lower in kcnq1−/− than in kcnq1+/+mice. Following an intraperitoneal glucose injection, the peak plasma glucose concentration was significantly lower in kcnq1−/− than in kcnq1+/+mice. Uptake of 3H-deoxy-glucose into skeletal muscle, liver, kidney and lung tissue was significantly higher in kcnq1−/− than in kcnq1+/+mice. In conclusion, KCNQ1 counteracts the stimulation of cellular K+ uptake by insulin and thereby influences K+-dependent insulin signaling on glucose metabolism. The observations indicate that KCNQ1 is a novel molecule affecting insulin sensitivity of glucose metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

Boini

Graf²,

Hennige³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Expression of KCNQ1, KCNQ4, and KCNQ5 in Xenopus oocytes yields voltage-dependent K ϩ currents that are very sensitive to changes in cell volume, with KCNQ5 as the most sensitive (304, 384). A role for KCNQ1 in RVD was also proposed in MCF-7 human mammary epithelial cells (1029) and in rat hepatocytes (507). A contribution of the putative KCNQ1 ␤-subunit KCNE1 (MinK) to RVD has been suggested in cells from the inner ear (1070), and in mouse tracheal epithelium where a KCNQ1/MinK complex was proposed to form a heterotetrameric channel (582).…”

Section: B Swelling-activated K ؉ Channelsmentioning

confidence: 99%

Physiology of Cell Volume Regulation in Vertebrates

Hoffmann

Lambert²,

Pedersen³

2009

Physiological Reviews

1,306

1,677

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The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most cases, activation of volume regulatory osmolyte transport. After acute swelling, cell volume is regulated by the process of regulatory volume decrease (RVD), which involves the activation of KCl cotransport and of channels mediating K+, Cl−, and taurine efflux. Conversely, after acute shrinkage, cell volume is regulated by the process of regulatory volume increase (RVI), which is mediated primarily by Na+/H+exchange, Na+-K+-2Cl−cotransport, and Na+channels. Here, we review in detail the current knowledge regarding the molecular identity of these transport pathways and their regulation by, e.g., membrane deformation, ionic strength, Ca2+, protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review.

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SGK1 dependence of insulin induced hypokalemia

Boini

Graf

Kuhl

et al. 2008

Pflugers Arch - Eur J Physiol

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Insulin stimulates cellular K+ uptake leading to hypokalemia. Cellular K+ uptake is accomplished by parallel stimulation of Na+/H+ exchange, Na+,K+,2Cl- co-transport, and Na+/K+ ATPase and leads to cell swelling, a prerequisite for several metabolic effects of the hormone. Little is known about underlying signaling. Insulin is known to activate the serum and glucocorticoid-inducible kinase SGK1, which in turn enhances the activity of all three transport proteins. The present study thus explored the contribution of SGK1 to insulin-induced hypokalemia. To this end, gene-targeted mice lacking SGK1 (sgk1-/-) and their wild-type littermates (sgk1+/+) have been infused with insulin (2 mU kg(-1) min(-1)) and glucose at rates leaving the plasma glucose concentration constant. Moreover, isolated liver perfusion experiments have been performed to determine stimulation of cellular K+ uptake by insulin (100 nM). As a result, combined glucose and insulin infusion significantly decreased plasma K+ concentration despite a significant decrease of urinary K+ excretion in sgk1+/+ but not in sgk1-/- mice. Accordingly, the plasma K+ concentration was within 60 min significantly lower in sgk1+/+ than in sgk1-/- mice. In isolated liver perfusion experiments, cellular K+ uptake was stimulated by insulin (100 nM), an effect blunted by 72% in sgk1-/- mice as compared to sgk1+/+ mice. Accordingly, insulin-induced cell hydration was 63% lower in sgk1-/- mice than in sgk1+/+ mice. Moreover, volume regulatory K+ release was 31% smaller in sgk1-/- mice than in sgk1+/+ mice. In conclusion, the serum and glucocorticoid-inducible kinase SGK1 participates in the signaling mediating the hypokalemic effect of insulin.

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Modulation of hepatocellular swelling-activated K⁺ currents by phosphoinositide pathway-dependent protein kinase C

Cited by 21 publications

References 50 publications

Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

Physiology of Cell Volume Regulation in Vertebrates

SGK1 dependence of insulin induced hypokalemia

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Modulation of hepatocellular swelling-activated K+ currents by phosphoinositide pathway-dependent protein kinase C

Cited by 21 publications

References 50 publications

Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

Physiology of Cell Volume Regulation in Vertebrates

SGK1 dependence of insulin induced hypokalemia

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Resources

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Modulation of hepatocellular swelling-activated K⁺ currents by phosphoinositide pathway-dependent protein kinase C