Contrasting Effects of Glycerol and Urea Transport on Rat Pancreatic &amp;beta;-Cell Function

Best, Leonard; Brown, Peter de Nully; Yates, Allen P.; Perret, Jason; Virreira, Myrna; Beauwens, Renaud; Malaisse, Willy; Sener, Abdullah; Delporte, Christine

doi:10.1159/000218172

Cited by 37 publications

(44 citation statements)

References 34 publications

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“…It is of interest that an extra pool of secretory vesicles not available for glucose is exploited for exocytosis after swelling-induced insulin secretion: after hypotonic stimulation from islets [4] and ethanol stimulation from INS-1 and INS-1E tumor cell lines [29]. Recently it was shown that other permeants urea and glycerol activate rat β-cells via their rapid uptake across the β-cell plasma membrane via AQP7 [37]. We can speculate that at least part of signaling of hypotonicity-induced cell activation is shared by permeants.…”

Section: Discussionmentioning

confidence: 99%

Cell Swelling-induced Insulin Secretion from INS-1E Cells is Inhibited by Extracellular Ca<sup>2+</sup> and is Tetanus Toxin Resistant

Orečná

Hafko

Toporcerová

et al. 2010

Cell Physiol Biochem

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Cell swelling-induced insulin secretion represents an alternative pathway of stimulation of insulin secretion. INS-1E rat tumor beta cells do not release insulin in response to cell swelling in presence of Ca²⁺ despite a good response to glucose challenge and appropriate increase in cell volume. Surprisingly, perifusion with Ca²⁺-depleted medium showed distinct secretory response of INS-1E cells to hypotonicity. Objective of this study was further characterization of the role of Ca²⁺ in secretory process in INS-1 and INS-1E cell lines. Ca²⁺ depleted hypotonic medium with 10 µM BAPTA/AM (intracellular chelator) induced insulin secretion from both types of cells. We demonstrated expression of L-type Ca²⁺ channel Ca_v1.2 and non-L-type Ca²⁺ channels Ca_v2.1 (P/Q-type), Ca_v2.2 (N-type), and Ca_v3.1 (T-type) in both cell lines. Inhibition of L type channel with nifedipine and/or P/Q type with ω-agatoxin IVA enabled distinct response to hypotonic medium also in INS-1E cells. Tetanus toxin (TeTx) in medium containing Ca²⁺ and a group of calcium channel blockers inhibited hypotonicity-induced insulin secretion from INS-1 cells but not from INS-1E cells. Conclusion: Hypotonicity-induced insulin secretion from INS-1E cells is inhibited by extracellular Ca²⁺, does not require intracellular Ca²⁺ and is TeTx resistant.

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Section: Discussionmentioning

confidence: 99%

Cell Swelling-induced Insulin Secretion from INS-1E Cells is Inhibited by Extracellular Ca<sup>2+</sup> and is Tetanus Toxin Resistant

Orečná

Hafko

Toporcerová

et al. 2010

Cell Physiol Biochem

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“…Thus, while increase of intracellular calcium concentration does not affect pendrin-mediated iodide efflux, it greatly stimulates iodide release from ANO1-expressing HEK 293T cells, PCCl3 cells, and dog thyrocytes. Of note, Pesce et al (27) showed weak activation of iodide loss by TSH but not by forskolin in PCCl3 cells, which suggests a TSH effect through the weakly responding phospholipase C-PIP 2 …”

Section: Concentration In Pccl3 Cells and In Ano1-expressing Hek 293tmentioning

confidence: 97%

“…RNA extraction from tissue and subsequent classical PCR analysis were performed as described in Best et al (2) except that reverse transcription was performed using iScript cDNA Synthesis Kit (BioRad, Hercules, CA). For the comparison of Ano1 expression in control and methimazole-treated rats, cDNA was prepared from thyroid tissue as described above, and a quantitative real-time PCR was performed on a CFX 96 Real-Time System C1000 Thermal Cycler (Bio-Rad) using iQ SYBR Green Supermix (Bio-Rad).…”

Section: Rt-pcr Analysis Of Ano1 Expression In Tissuesmentioning

confidence: 99%

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Twyffels

Strickaert

Virreira

et al. 2014

American Journal of Physiology-Cell Physiology

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Iodide is captured by thyrocytes through the Na ϩ /I Ϫ symporter (NIS) before being released into the follicular lumen, where it is oxidized and incorporated into thyroglobulin for the production of thyroid hormones. Several reports point to pendrin as a candidate protein for iodide export from thyroid cells into the follicular lumen. Here, we show that a recently discovered Ca 2ϩ -activated anion channel, TMEM16A or anoctamin-1 (ANO1), also exports iodide from rat thyroid cell lines and from HEK 293T cells expressing human NIS and ANO1. The Ano1 mRNA is expressed in PCCl3 and FRTL-5 rat thyroid cell lines, and this expression is stimulated by thyrotropin (TSH) in rat in vivo, leading to the accumulation of the ANO1 protein at the apical membrane of thyroid follicles. Moreover, ANO1 properties, i.e., activation by intracellular calcium (i.e., by ionomycin or by ATP), low but positive affinity for pertechnetate, and nonrequirement for chloride, better fit with the iodide release characteristics of PCCl3 and FRTL-5 rat thyroid cell lines than the dissimilar properties of pendrin. Most importantly, iodide release by PCCl3 and FRTL-5 cells is efficiently blocked by T16A inh-A01, an ANO1-specific inhibitor, and upon ANO1 knockdown by RNA interference. Finally, we show that the T16A inh-A01 inhibitor efficiently blocks ATP-induced iodide efflux from in vitro-cultured human thyrocytes. In conclusion, our data strongly suggest that ANO1 is responsible for most of the iodide efflux across the apical membrane of thyroid cells.anoctamin-1; iodide release; pendrin; thyrocyte; TMEM16A

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“…In parallel, it would also increase the need for other precursors than glycerol to support energy needs within muscle tissue. Finally, AQP7 has also been localized to pancreatic b-cells (Matsumura et al 2007, Best et al 2009). Despite the apparent intracellular localization of AQP7, the AQP7 KO mice were reported to have a higher intra-islet glycerol and TG content with an increased activity of GlyK similar to that observed in WAT from the first KO line.…”

Section: Effects Of Aqp7 Deficiency On Glycerol Metabolismmentioning

confidence: 99%

Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver

Lebeck

2014

Journal of Molecular Endocrinology

104

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Obesity and secondary development of type 2 diabetes (T2D) are major health care problems throughout the developed world. Accumulating evidence suggest that glycerol metabolism contributes to the pathophysiology of obesity and T2D. Glycerol is a small molecule that serves as an important intermediate between carbohydrate and lipid metabolism. It is stored primarily in adipose tissue as the backbone of triglyceride (TG) and during states of metabolic stress, such as fasting and diabetes, it is released for metabolism in other tissues. In the liver, glycerol serves as a gluconeogenic precursor and it is used for the esterification of free fatty acid into TGs. Aquaporin 7 (AQP7) in adipose tissue and AQP9 in the liver are transmembrane proteins that belong to the subset of AQPs called aquaglyceroporins. AQP7 facilitates the efflux of glycerol from adipose tissue and AQP7 deficiency has been linked to TG accumulation in adipose tissue and adult onset obesity. On the other hand, AQP9 expressed in liver facilitates the hepatic uptake of glycerol and thereby the availability of glycerol for de novo synthesis of glucose and TG that both are involved in the pathophysiology of diabetes. The aim of this review was to summarize the current knowledge on the role of the two glycerol channels in controlling glycerol metabolism in adipose tissue and liver. Glycerol metabolismThe metabolic switching between feeding and fasting is central to everyday life and involves tight hormonal control with effects on muscle, adipose tissue, and liver that maintains an adequate handling of metabolic precursors to support energy demands. One of the molecules affected by metabolic switching is glycerol, which is a small 3-carbon alcohol that in the fed state is stored as the backbone of triglyceride (TG) mainly in adipose tissue.In the fed state, after ingestion of dietary fats (w90% TG), !30% of TG is fully hydrolyzed into free fatty acids (FFA) and glycerol. Glycerol rapidly enters the enterocytes of the small intestine and thereafter the circulation through the portal vein and is primarily metabolized by the liver (Lin 1977). In adipose tissue, the activity of glycerol kinase (GlyK), that catalyzes the initial phosphorylation of glycerol into glycerol-3-phosphate (G3P), is negligible and therefore glycerol is not normally utilized in adipose tissue. Instead G3P used for the synthesis of TG in the fed state is derived from glycolysis.During states of increased energy demand, such as fasting and exercise, adipocyte lipolysis is increased by activation of adipose TG lipase and hormone-sensitive

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Contrasting Effects of Glycerol and Urea Transport on Rat Pancreatic β-Cell Function

Cited by 37 publications

References 34 publications

Cell Swelling-induced Insulin Secretion from INS-1E Cells is Inhibited by Extracellular Ca<sup>2+</sup> and is Tetanus Toxin Resistant

Cell Swelling-induced Insulin Secretion from INS-1E Cells is Inhibited by Extracellular Ca<sup>2+</sup> and is Tetanus Toxin Resistant

Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte

Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver

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