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onsdag 27 januari 2016

Eräs toistamani ajatus

Jos suostutaan vähentämään vehnärasitusta, gluteenin osuutta vehnässä , ja keliakikoilla vehnäperäisiä  valmisteita,   polyglutamaattien   ja joidenkin tiettyjen toksisten  pätkien aiheuttama  kokovuotinen  rasitus pienenee olennaisesti,  SEKÄ jos   vähennetään raffinoitu sokeri minimiin  ja  rasvojen käytössä ollaan kohtuullisia, vähenee  diabetesrasitus.  Liikunnan tulee olla kohtuullista, ei ylirasittavaa.
"Bad guys" ovat  liikamäärissä konsumoituja" good guys"   tekijöitä. 

Glutamiini ja glukoosi ovat  ihmisen  energian suhteen peruspolttoaineita solutasossa. Peruspolttoainetta ei kannata  syödä sen solutasokoossa, kun kerran on hampaat suussa  syömistä varten.  Ei ravinnon tarvitse olla ruoansulatuksen lopputuotemuodossa. Normaali  aineenvaihdunnallinen muokkausjärjestelmä on  sitä varten olemassa.

Gluteeni sisältää tiiviit pakkaukset polyglutamiinia  (QQQQ tyyppisiä pätkiä  ja voi  olla yksi syy  aineenvaihdunnan muuttumiseen diabeettiseksi.. Ja jos  liikamäärän takia arvokas kehon polttoaine ei jostain syystä ehdi pilkkoutua  aminohappokokoon ( erillinen Q ja E ) , jää  allergeenisiä peptidejä ja tulee niitä tTG vasta-aineita josta on  joka kudoksessa lopulta haittaa.  Ei voi sanoa että kyse olisi  antiikin ajoissa asti esiintyneen entsyymin puutteesta, sillä kyse  voi olla vain  yksipuolisen yhä vaikeammin suolatettavan    rakenteen massiivisesta ja lisääntyvästä tarjonnasta aineenvaihdunnalle näin aikojen lopussa.

Keliakikon dieetin optimointi tulisi olla niin tarkka että tTG vasta-aineet ovat negatiiviset.
Ja tietysti on paha seikka jos  kaikkien hyvien neuvojen jälkeen, paino on epävakaa ja lisääntyy lisääntymistään , jolloin  tulee ikädiabeteksen  ongelmistoa.

Mutta varsinkin  lapsuudessa  on suotavaa  välttää  moderneja  päätetuotemuotoja  ruoan ravintoaineista.
Niistä puuttuu ensinnäkin fytiini, orgaaaninen fosfaatti ( kehon tärkeimpioä antioksidantteja) .  Ihme ettei useammalla ole  lapsuuden diabetes, kun  on sellainen  suoraan vereen  menevä ravinto.

Lapsille olisi hyvä oppi nakertamaan joitain soveltuvia papuja,,siemeniä, pähkinöitä  karamellien sijasta,  mitä tahansa  luonnon tarjomaa terveellistä jotakin, mutta ei niin paljon sokeria ja karamelleja. Tietysti lapset tarvitsevat useita välipaloja. On vaikea edes antaa neuvoja, koska nykyajan lapsilla on allerginen  valmius niin suuri,  koska öljyt ovat hyvät ja arakidonia on varmasti joka solussa runsaasti.  Minun lapsuudessani   ei ollut kasvisöljyä käytössä, joten   anergia oli yleistä-  meillä tosin  sellaiset ksviöljyn vajeet  korvasi isäni innostus amerikkalaiseen tapaan käyttää pähkinöitä runsaasti  kotona- balansoituna rusinotten kansa.  Toinen seikka sitten on se että  oli aina taiveihottumaa.   Siis ON VAIKEA antaa kenellekään mitään hyviä neuvoja.   Jollain tavalla kuitienkin olen sitä mieltä että allergioiden yleistyminen  saattaa merkitä sitä, että tavallisen voinkin  voisi ottaa  käyttöön varsinkin lapsuudessa.  Siitä ei tule niin paljon   arakidonihappoa. Toisaalta maito ja maitorasvat ovat hyvä lähde keuhkonsuoja-aineille, koska niistä saa palmitiinihappoa keuhkolesitiinin muodostukseen.

I- tyypin diabeteksen esimuodon ja samalla keliakian seulonta

LÄHDE:
J Immunol Methods. 2016 Jan 22. pii: S0022-1759(16)30010-2. doi: 10.1016/j.jim.2016.01.011. [Epub ahead of print]

A multiplex assay combining insulin, GAD, IA-2 and transglutaminase autoantibodies to facilitate screening for pre-type 1 diabetes and celiac disease.

Abstract

At the current time, multiple candidate interventions are being proposed to abrogate or slow progression to type 1 diabetes (T1D) among islet autoantibody (iAb) positive subjects, but mass screening for eligible subjects and the general population remains a laborious and inefficient process. We have recently developed and extensively validated nonradioactive iAb assays using electrochemiluminescense (ECL) detection with an excellent sensitivity and specificity compared to the gold-standard radioassays. Using ECL detection on a platform from MesoScale Discovery (MSD) allows the measurement of four antibodies in a single well using a small blood volume (6ul). In the present study using a MSD QuickPlex 4-Spot plate, we successfully combined three iAb to insulin (IAA), GAD65 (GADA), and IA-2 (IA-2A) with tissue transglutaminase autoantibodies (TGA) in a single well of a 96 well plate. We tested 40 new onset T1D patients, all positive for at least one iAb and a half of them positive for TGA by radioassay, as well as 50 healthy controls. The multiplex assay retained 100% sensitivity and 100% specificity for all four autoantibodies in terms of positivity identified in patients versus normal controls compared to the corresponding standard radioassays and our single ECL assays. The multiplex ECL assay was able to identify more positivity than current radioassays for IAA and TGA. The development of this multiplex assay will facilitate high-throughput screening for T1D and celiac disease risk in the general population.
Copyright © 2015. Published by Elsevier B.V.

KEYWORDS:

assay; autoantibodies; celiac disease; diabetes

Transglutaminaasin rooli glukoosin stimuloimassa insuliinin erityksessä

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1146677/

Abstract

Preincubation of rat islets of Langerhans with the potent inhibitors of islet transglutaminase activity, monodansylcadaverine (30-100 microM) and N-(5-aminopentyl)-2-naphthalenesulphonamide (100-200 microM), led to significant inhibition of glucose-stimulated insulin release from islets.

In contrast, the respective N'-dimethylated derivatives of these two compounds, which did not inhibit islet transglutaminase activity, were much less effective as inhibitors of glucose-stimulated insulin release. None of the compounds inhibited rat spleen protein kinase C activity at concentrations which gave rise to inhibition of glucose-stimulated insulin release. 

When tested for their effects on calmodulin-stimulated bovine heart phosphodiesterase activity, of the compounds that inhibited insulin release, only monodansylcadaverine did not act as an effective antagonist of calmodulin at concentrations (up to 50 microM) that gave rise to significant inhibition of glucose-stimulated insulin release

. Furthermore, at 50 microM, monodansylcadaverine did not inhibit methylation of islet lipids.

 The inhibition of glucose-stimulated insulin release by monodansylcadaverine is therefore likely to be attributable to its interference with islet transglutaminase activity.

 The sensitivity of islet transglutaminase to activation by Ca2+ was investigated by using a modified assay incorporating dephosphorylated NN'-dimethylcasein as a substrate protein. The Km for Ca2+ obtained (approx. 3 microM) was an order of magnitude lower than previously reported for the islet enzyme [Bungay, Potter & Griffin (1984) Biochem. J. 219, 819-827]. Mg2+ (2 mM) was found to have little effect on the sensitivity of the enzyme to Ca2+.

 Investigation of the endogenous substrate proteins of islet transglutaminase by using the Ca2+-dependent incorporation of [14C]methylamine into proteins of islet homogenates demonstrated that most of the incorporated radiolabel was present in cross-linked polymeric aggregates which did not traverse 3% (w/v) acrylamide gels.

The radiolabelled polymeric aggregates were present in 71 000 g-sedimented material of homogenates, and their formation was transglutaminase-mediated.

 These findings provide new evidence for the involvement of islet transglutaminase in the membrane-mediated events necessary for glucose-stimulated insulin release.

Glykeminen L-Glutamiini

LÄHDE

PLoS One. 2014 Nov 20;9(11):e113366. doi: 10.1371/journal.pone.0113366. eCollection 2014.
Glycemic effects and safety of L-Glutamine supplementation with or without sitagliptin in type 2 diabetes patients-a randomized study.

Abstract

BACKGROUND AND AIMS:

L-glutamine is an efficacious glucagon-like peptide (GLP)-1 secretagogue in vitro. When administered with a meal, glutamine increases GLP-1 and insulin excursions and reduces postprandial glycaemia in type 2 diabetes patients. The aim of the study was to assess the efficacy and safety of daily glutamine supplementation with or without the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin in well-controlled type 2 diabetes patients.

CONCLUSIONS:

Daily oral supplementation of glutamine with or without sitagliptin for 4 weeks decreased glycaemia in well-controlled type 2 diabetes patients, but was also associated with mild plasma volume expansion.

TRIAL REGISTRATION:

ClincalTrials.gov NCT00673894.

Glukoosi ja glutamiiniainenvaihdunta nousee syövässä

Oncotarget. 2016 Jan 11. doi: 10.18632/oncotarget.6879. [Epub ahead of print]

Dlx-2 and glutaminase upregulate epithelial-mesenchymal transition and glycolytic switch.

Abstract

Most cancer cells depend on enhanced glucose and glutamine (Gln) metabolism for growth and survival. Oncogenic metabolism provides biosynthetic precursors for nucleotides, lipids, and amino acids; however, its specific roles in tumor progression are largely unknown.

 We previously showed that distal-less homeobox-2 (Dlx-2), a homeodomain transcription factor involved in embryonic and tumor development, induces glycolytic switch and epithelial-mesenchymal transition (EMT) by inducing Snail expression. Here we show that Dlx-2 also induces the expression of the crucial Gln metabolism enzyme glutaminase (GLS1), which converts Gln to glutamate. TGF-β and Wnt induced GLS1 expression in a Dlx-2-dependent manner. GLS1 shRNA (shGLS1) suppressed in vivo tumor metastasis and growth.

 Inhibition of Gln metabolism by shGLS1, Gln deprivation, and Gln metabolism inhibitors (DON, 968 and BPTES) prevented Dlx-2-, TGF-β-, Wnt-, and Snail-induced EMT and glycolytic switch. Finally, shDlx-2 and Gln metabolism inhibition decreased Snail mRNA levels through p53-dependent upregulation of Snail-targeting microRNAs. These results demonstrate that the Dlx-2/GLS1/Gln metabolism axis is an important regulator of TGF-β/Wnt-induced, Snail-dependent EMT, metastasis, and glycolytic switch.

Glutaminaasi entsyymi

Regulation of Hepatic Glutaminase in the Streptozotocin-Induced Diabetic Rat
Stephen A Squires,
  1. John T Brosnan
+ Author Affiliations
  1. Department of Biochemistry, Memorial University of Newfoundland St. John's, Newfoundland, Canada
  1. Address correspondence and reprint requests to Dr. John T. Brosnan, Memorial University of Newfoundland, Department of Biochemistry, St. John's, Newfoundland, Canada A1B 3X9.

Abstract

The liver of diabetic animals removes increased quantities of glutamine.
 We therefore examined factors that affect hepatic glutaminase activity in hepatocytes and mitochondria. Glutamine use, through glutaminase, was measured in isolated rat hepatocytes by monitoring the production of 14CO2 from [I-14C]glutamine. Hepatocytes from streptozotocin-induced diabetic rats use glutamine more rapidly than do hepatocytes from normal or insulin-maintained diabetic rats. Glutamine use in all of these hepatocytes was stimulated by glucagon and epinephrine. Glutaminase activity, assayed in broken mitochondrial membranes, was increased ∼2.5-fold in diabetic rats. The sensitivity of glutaminase, measured in intact liver mitochondria, to phosphate was markedly left-shifted in mitochondria from diabetic rats compared with those from controls. In fact, glutaminase was increased 10-fold at 2.5 mmol/l phosphate compared with controls. This increased sensitivity of glutaminase to physiological concentrations of phosphate is characteristic of its hormonal activation. Therefore, activation of glutaminase plays a major role in diabetes and is as important as increases in its total enzyme amount in determining the increased glutamine uptake in diabetes.
  • Received February 20, 1997.
  • Revision received August 7, 1997.
  • Accepted August 7, 1997.