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.
onsdag 27 januari 2016
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.
Copyright © 2015. Published by Elsevier B.V.
KEYWORDS:
assay; autoantibodies; celiac disease; diabetesTransglutaminaasin 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
Glycemic effects and safety of L-Glutamine supplementation with or without sitagliptin in type 2 diabetes patients-a randomized study.
Samocha-Bonet D1, Chisholm DJ1, Gribble FM2, Coster AC3, Carpenter KH4, Jones GR5, Holst JJ6, Greenfield JR7.
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.
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,
+ Author Affiliations
- 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.
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.
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