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Solute Transporters And Aquaporins Impaired In Celiac Disease


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This looks like it could explain our dehydration problems ... what do you think ?

http://www.ncbi.nlm....pubmed/20415666

2010 May 26;102(8):457-67.

Solute transporters and aquaporins are impaired in celiac disease.

Laforenza U, Miceli E, Gastaldi G, Scaffino MF, Ventura U, Fontana JM, Orsenigo MN, Corazza GR.

Source

Department of Physiology, University of Pavia, Pavia, Italy. lumberto@unipv.it

Abstract

BACKGROUND INFORMATION:

Celiac disease is a chronic inflammatory disorder of the small bowel induced in genetically susceptible subjects by gluten ingestion. Diarrhoea, weight loss and malabsorption represent the major clinical presentation of the disease. Here we examined the possible alteration in the expression and localization of water channels [AQPs (aquaporins)] and some solute transporters in duodenal mucosa of celiac disease patients. Duodenal biopsies from untreated celiacs, treated celiacs, healthy controls and disease controls were considered in the present study. The expressions of some AQPs and transporter mRNAs in human duodenal biopsies were determined by semi-quantitative RT-PCR (reverse transcription PCR) and real-time RT-PCR. The localization of AQPs 3, 7 and 10 and of SGLT1 (Na+/glucose co-transporter 1), PEPT1 (H+/oligopeptide transporter 1) and NHE3 (Na+/H+ exchanger 3) was evaluated by immunohistochemistry.

RESULTS:

AQPs 3, 7, 10 and 11, SGLT, PEPT and NHE, CFTR (cystic fibrosis transmembrane conductance regulator) and NKCC (Na-K-2Cl co-transporter) mRNAs were expressed in duodenal biopsies of healthy controls, treated celiac patients and disease controls. The expression of transcripts was virtually absent in duodenal biopsies of untreated celiac disease patients except for CFTR and NKCC. In healthy controls, immunohistochemistry revealed a labelling in the apical membrane of surface epithelial cells of the duodenum. The immunolabelling was heavily reduced or absent in untreated celiac patients, while it was normal in patients consuming a gluten-free diet for at least 12 months.

CONCLUSIONS:

Our results indicate that the main routes for water and solute absorption are deficient in celiac disease and may play a role in the onset of malabsorption symptoms.

PMID: 20415666 [PubMed - indexed for MEDLINE]

I was googling celaic sodium glucose when I found that article. I was looking for it because when we were discussing individual rehydration techniques this article came up ...

http://en.wikipedia....dration_therapy

Oral rehydration therapy

From Wikipedia, the free encyclopedia

Oral rehydration therapy (ORT) is a simple treatment for dehydration associated with diarrhea, particularly gastroenteritis or gastroenteropathy, such as that caused by cholera or rotavirus. ORT consists of a solution of salts and sugars which is taken by mouth. It is used around the world, but is most important in the developing world, where it saves millions of children a year from death due to diarrhea, the second leading cause of death (after pneumonia) in children under five.[1]

................................................................................................................

Physiological basis

Fluid from the body is normally pumped into the intestinal lumen during digestion. This fluid is typically isosmotic with blood because it contains a high concentration of sodium (approx. 142 mEq/L). A healthy individual will secrete 20-30 grams of sodium per day via intestinal secretions. Nearly all of this is reabsorbed by the intestine, helping to maintain constant sodium levels in the body (homeostasis).[44]

Because there is so much sodium secreted by the intestine, without intervention, heavy continuous diarrhea can be a very dangerous and potentially life-threatening condition within hours. This is because liquid secreted into the intestinal lumen during diarrhea passes through the gut so quickly that very little sodium is reabsorbed, leading to very low sodium levels in the body (severe hyponatremia).[44] This is the motivation for sodium and water replenishment via ORT.

Sodium absorption via the intestine occurs in two stages. The first is at the outermost cells (intestinal epithelial cells) at the surface of the intestinal lumen. Sodium passes into these outermost cells by co-transport facilitated diffusion (symport diffusion) via the SGLT1 protein.[44] From there, sodium is pumped out of the cells (basal side) and into the extracellular space by active transport via the sodium potassium pump.[45][46]

The co-transport of sodium into the epithelial cells via the SGLT1 protein requires glucose or galactose. Two sodium ions and one molecule of glucose/galactose are transported together across the cell membrane through the SGLT1 protein. Without glucose or galactose present, intestinal sodium will not be absorbed.[44] This is the reason glucose is included in ORSs. For each cycle of the transport, hundreds of water molecules move into the epithelial cell, and this brings about the rehydration

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I love this research--it really connects with some things I had been thinking. We had a little talk back in August about carrier proteins, but I guess it got lost in a thread. Here it is, starting at the #3 post.

http://forums.dinet.org/index.php?/topic/17876-update-2-month-long-mayo-visit/page__p__163244__hl__solute__fromsearch__1#entry163244

I had my appt. with my geneticist, and asked him if any of this could possibly be behind POTS, and he had no idea. He took a few vials of blood to test my various amino acids, but I haven't heard anything back yet(yea, 7 weeks now).

I have always wondered if the problem in the intestine with the solute carrier family could really be traced back to undiagnosed gluten intolerance, or at least something similar that is yet unfound! Your article kind of brings this all together.

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I love this research--it really connects with some things I had been thinking. We had a little talk back in August about carrier proteins, but I guess it got lost in a thread. Here it is, starting at the #3 post.

http://forums.dinet....__1#entry163244

I had my appt. with my geneticist, and asked him if any of this could possibly be behind POTS, and he had no idea. He took a few vials of blood to test my various amino acids, but I haven't heard anything back yet(yea, 7 weeks now).

I have always wondered if the problem in the intestine with the solute carrier family could really be traced back to undiagnosed gluten intolerance, or at least something similar that is yet unfound! Your article kind of brings this all together.

I'm a research junkie too ... lol ... thanks for the link ... I vaguely remember that discussion because it didn't make sense at the time ...

I'm brain dead right now cause I spent the morning typing this ... I didn't find anything else on the SGCT systems but I think you'll find it interesting anyways.

http://www.glutenfreeandbeyond.org/forum/viewtopic.php?t=5711

marcia

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This study said that it normalizes after 12 months on the gf diet. The problem is that not every celiac heals just by going on the Gf diet ...

Unfortunately, no one knows who will heal and who won't and which symptoms will go away. The medical profession likes to think it's easy for celiacs to heal but that's not what I'm seeing. These are the same people who aren't looking for nutritional deficiencies either tho and the same people who give us drugs and don't want to hear about our side effects. :wacko:

I know a few celiacs who are very sick still. From what I can tell though, they're still getting cross contaminated regularly via those gf processed foods. I heard that it's best to avoid those and all grains for awhile. That's one of the reasons, I went on a Paleo / low carb / low oxalate diet. I reacted to minute amounts of gluten so it was obvious to me ..

tc ... d

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Sue said ..

I had my appt. with my geneticist, and asked him if any of this could possibly be behind POTS, and he had no idea. He took a few vials of blood to test my various amino acids, but I haven't heard anything back yet(yea, 7 weeks now).

Hi again ... it just hit me that you're probably expecting your doctors to know about the research that we're seeing on the web. And if they don't know, then surely they'd be interested in what one of their patients had learned especially if it's from a reliable source ... :wub: ... but the answer is NO ... :huh:

I did this with my docs too ... I really like my doctors but realized after several attempts to pick their brains on what I was reading on the web figured out that they weren't up on the info I was finding. I'm assuming they're happy that I'm leaving them alone now .. lol ...

I'm not sure if it's because they only know what they were taught in med school or since what we're learning is not in their guidebooks, they can't comment on it ...

And maybe it's because we're looking for answers when everyone they know and respect has told them that there aren't any answers for dysautonomia or CFS or ME or or or .. :blink:

FWIW .. I thought this way too until I realized what food was doing to me.

I have a great integrative doctor who believes in finding causes too. If you're not seeing one, you can find one in your area by googling integrative doctors your city, county or state ...

Hi 718,

I'm still a foodie so I know what you mean ... I try to stick to whole foods at this point .. what I'm finding is that those processed foods made with rice, etc taste like rice + whatever ... yech ... I prefer real food now ...

tc .. d

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http://www.asknature...d7ea2846cfb7f42

Interesting info ...

Pores, called aquaporins, in membranes selectively move water by aligning the polar molecules using charged regions and passing them through a narrow area
"Because water is the major component of all living cells, the ability to absorb and release water must be considered a fundamental property of life.

Cell membranes are exquisitely selective barriers that control the solute composition of the enclosed compartments by regulating the entry of ions; small, uncharged solutes; and water into cells.

In addition, cells organized in epithelial tissues have apical and basolateral membranes, which constitute serial barriers that regulate the transepithelial movement of solutes and water, thereby contributing to the homeostasis of multicellular organisms…

The recognized characteristics of membrane water channels led to chance identification of the first known water channel." (Borgnia et al. 1999:426)

"The high water permeability characteristic of mammalian red cell membranes is now known to be caused by the protein AQP1. This channel freely permits movement of water across the cell membrane, but it is not permeated by other small, uncharged molecules or charged solutes.

AQP1 is a tetramer with each subunit containing an aqueous pore likened to an hourglass formed by obversely arranged tandem repeats.

Cryoelectron microscopy of reconstituted AQP1 membrane crystals has revealed the three-dimensional structure at 3–6 Å. AQP1 is distributed in apical and basolateral membranes of renal proximal tubules and descending thin limbs as well as capillary endothelia.

Ten mammalian aquaporins have been identified in water-permeable tissues and fall into two groupings.

Orthodox aquaporins are water selective and include AQP2, a vasopressin-regulated water channel in renal collecting duct, in addition to AQP0, AQP4, and AQP5.

Multifunctional aquaglyceroporins AQP3, AQP7, and AQP9 are permeated by water, glycerol, and some other solutes. Aquaporins are being defined in numerous other species including amphibia, insects, plants, and microbials.

Members of the aquaporin family are implicated in numerous physiological processes as well as the pathophysiology of a wide range of clinical disorders." (Borgnia et al. 1999:425)

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So true ... I understand this but at the same time, I can't wait for them to figure this out. I've been disabled since 1990 and I'm not getting any younger ... lol ...

My integrative doctor is interested in learning new things but she has time limits too. I'm assuming all integrative doctors are this way since it takes a lot of effort to learn both traditional and holistic treatments ..

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I am actually on IV saline therapy (via my port/cath) for this very reason. As quoted by the Celiac Disease Foundation: "Damaged villi (in the small intestine) do not effectively absorb basic nutrients- proteins, carbohydrates, fats, vitamins, minerals, and in some cases, water and bile salts." When I first got sick from my untreated and at that time undiagnosed celiac disease, I could not stay hydrated no matter how much gatorade I sucked down, and lost over 35 pounds in less than five months. (I am about 5'8, and I went from around 160 pounds to 123 or so, and have struggled to put weight back on ever since.) There is just simply no way for me to stay hydrated, or manage my hypotension, by simply drinking fluids by mouth. Occasionally, a girl has to come up for air! :blink: We are still trying to figure out the amounts I need via port to be stable. It's a work in progress. I too, am strictly gluten free, as the slightest cross-contamination can have horrific results. The last one cost me 10 pounds in 10 days, and I am still not recovered. I have the added frustration that as of yet, the haven't found the damage to my intestine. We know it is there, because of the after affects, it just hasn't been found yet. So I have a hot date with the gastroenterology department at the Cleveland Clinic on November 11 in part to talk about special scoping the goes further down the "line" than a standard endoscopy. Fingers crossed!

Sandy

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When I first got sick from my untreated and at that time undiagnosed celiac disease, I could not stay hydrated no matter how much gatorade I sucked down, and lost over 35 pounds in less than five months. (I am about 5'8, and I went from around 160 pounds to 123 or so, and have struggled to put weight back on ever since.) There is just simply no way for me to stay hydrated, or manage my hypotension, by simply drinking fluids by mouth. Occasionally, a girl has to come up for air! :blink: We are still trying to figure out the amounts I need via port to be stable. It's a work in progress. I too, am strictly gluten free, as the slightest cross-contamination can have horrific results. The last one cost me 10 pounds in 10 days, and I am still not recovered. I have the added frustration that as of yet, the haven't found the damage to my intestine. We know it is there, because of the after affects, it just hasn't been found yet. So I have a hot date with the gastroenterology department at the Cleveland Clinic on November 11 in part to talk about special scoping the goes further down the "line" than a standard endoscopy. Fingers crossed!

Sandy

Hi sandy,

sorry to hear you're going thru this. I think I got celiac disease in june 2005, 15 years after getting sick with

Me/cfs. I lost 10 pounds in one month due to non stop diarhea. I'm 5' 5" and was 118 at the time. It took me

at least 18 months for my digestion to begin to normalize. At 17 months post gf, I still had damage. My last

endoscopy was normal tho. But i'm still having digestion problems.

I keep my weight up by eating healthy fats, like evoo, gso and raw nuts and seeds. I get thin quickly if I

skip these.

I was wondering how your dehydration was diagnosed. Are there tests for this. My urine tests over a 5 week period showed dehydration but that's the only way I knew for sure. Well other than my cfs doc telling me that I was and needed tons of

water and salt. I learned that if my finger tips were prunish i needed salt water.

I wanted to say too that my reaction from cc has lessened recently. Kow .. I used to get facial twithing for 3 weeks but

don.t get it at all now. Of course like most celiacs, minor infractions are far worse than eating gluten was

Prior to going gf.

Good luck at the cleveland clinic. I didn't realize further testing for celiac damage was available. Tc ..d

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Me too! I made gluten free meatballs tonight and homemade salsa. :)

Yum .. I miss meatballs and salsa. Luckily, since I came from a big family, i'll eat anything tho .. Lol

Fwiw. If you're eating gf grains, there was a study recently by trish thompson (sp?) That stated

only grains labelled gf were safe. That article is on glutenfreeandbeyond. Sadly, The fda hasn't established any guidelines for gluten in the us, so all gf vendors are on the honor system .. Lol ..

Tc ... D

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Btw .. Does anyone here have problems with chronic constipation / hard stools ? Despite drinking plenty of water and taking konsyl and digestive enzymes, I still have this. I started experimenting with mag citrate / natural calm powder a few weeks ago but can't find the right dosage yet. I'm currently trialing sipping a total of 3 tsp mixed with water throughout the day .. The idea is to pull fluids into my digestive tract all day long. Any thoughts ? Thanks ... D

Ps. I.ve already noticed a decrease in abdominal hard spots and pains in my colon, if that makes sense.

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