Lufega's anti-unknown regimen...., Fun for the whole family!! Rating Options

[rwac]

http://jn.nutrition.org/cgi/content/abstract/114/8/1438

Effect of Manganese Deficiency on Insulin Secretion and Carbohydrate Homeostasis in Rats<h2></h2> Deborah L. Baly, Donald L. Curry^*, Carl L. Keen and Lucille S. Hurley

Departments of Nutrition ^* Departments of Nutrition Physiological Sciences, University of California, Davis, CA 95616



The effects of manganese (Mn) deficiency on carbohydrate metabolism in the Sprague-Dawley rat were investigated. Oral glucose tolerance tests were performed on offspring from Mn-sufficient female rats fed 45 µg Mn per gram diet (C-C), offspring from Mn-deficient female rats fed 1 µg Mn per gram diet (D1-D1) and rats not exposed to Mn deficiency in utero but fed D1 diet from weaning to maturity (D1). Mn-deficient rats, D1 and D1-D1, had significantly lower concentrations of Mn in liver, kidney, heart and pancreas than controls. D1-D1 rats responded with a diabetic type of glucose tolerance curve when given oral glucose. Insulin levels of D1-D1 rats were not commensurate with their high glucose levels. Measurements made by using an isolated perfused-pancreas preparation indicate that insulin output due to release of stored hormone was 76% of control levels in D1-D1 rats. This suggests either lower insulin stores or impaired release of insulin in D1-D1 rats. Second phase insulin release was also significantly lower in D1-D1 rats than in controls. Pancreatic insulin content was 63% of control levels in D1-D1 rats, further supporting the idea of lower insulin stores in Mn-deficient rats. No differences in plasma glucose levels were observed between D1 rats and controls after an oral-glucose load. These findings indicate that dietary Mn deficiency can result in impaired insulin secretion producing impaired carbohydrate metabolism; however, the timing of the deficiency may be a critical factor in the expression of this abnormality.

[Lufega]

rwac,

Would the full article state what the best time to intervene is? I have a friend who is diabetic post steroid use. I got him on 10 mg manganese gluconate and he lost all this stubborn body fat he had which I attribute to a decrease in fasting blood glucose. I'm waiting for his glycemia to confirm.

[Lufega]

Boom! I can finally explain all of my signs and symptoms (except the alpha 1 antitrypsin deficiency) in terms of dysautonomia (autonomic neuropathy). These include all my connective tissue problems and might also explain the multiple mineral deficiencies. Now I'm getting somewhere..

[Heart and autonomic nervous system in connective tissue disorders]

[Article in Italian]

Laganà B, Gentile R, Vella C, Giovani A, Tubani L, Mastrocola C, Baratta L, Bonomo L.
Dipartimento di Medicina Clinica, Università La Sapienza, Roma.
Heart rate variability (HRV) is a suitable diagnostic tool in identifying patients with autonomic nervous system (ANS) disorders even in pre-clinical stage. We have enrolled in this study all patients with large variety of connective tissue disorders, given the possibility of an involvement of ANS in these diseases. The study population consisted in eighty-five patients (68 females and 17 males), 35 of whom affected by systemic lupus erythematosus, 16 by rheumatoid arthritis, 14 by Sjögren syndrome, 12 by progressive systemic sclerosis, 3 by Behçet syndrome and 5 by antiphospholipid antibodies syndrome. The mean age ranged between 33.7 of patients with lupus erythematosus and 51.8 of those with Sjögren syndrome. As control, we enrolled healthy subjects of different age, divided into two groups, to rule out the aging as potential source of considered parameters alteration. The autonomic function has been evaluated by 24 hours ambulatory monitoring, using a Zymed 1210 Scanner with Zymed 3.74-PC 1990 software. We have considered: in the time domain, the standard deviation of the RR intervals average (SDNN) and the percentage of RR adjacent intervals differing each other more than 50 msec (pNN50); in the frequency domain, the low (LF) and high (HF) frequencies, the LF/HF ratio, and the total power (RT). The HRV parameters resulted abnormal in every type of the connective tissue diseases considered: particularly SDNN, pNN50, LF, HF and RT (p < or = 0.01). In conclusion: the results of our study suggest that autonomic neuropathy may be present in any kind of connective tissue disorders even in preclinical stage.

Dysautonomia basically involves a dysfunction of the cholinergic system. Manganese is needed for both acetylcholine production and connective tissue integrity. However, Mn is not the end of the road, but another link in the chain.

[rwac]

The article just says that reintroduction of Manganese into the diet improves the diabetes/insulin-resistance caused by deficiency. I copied some text, messy because it's a pdf.

A relationship between manganese and
abnormal carbohydrate metabolism was
first suggested by Rubenstein and co-workers
in 1962 (5). They reported the case of a
diabetic patient, resistant to insulin therapy,
who responded to oral doses of manganese
chloride with a consistent drop in blood
glucose levels. Manganese supplementation
was tried because of the ineffectiveness of
high doses of insulin in maintaining normal
blood glucose and the patient's statement
that his diabetic condition could be con
trolled to some extent by an extract of lucerne
(alfalfa, Medicago sativa). Analysis of the
alfalfa extract revealed a high concentration
of manganese In contrast to the effective
ness of manganese, oral supplements of zinc,
magnesium, cobalt or iron had no effect on
the patient's blood sugar levels, indicating a
specific role for manganese in insulin release
or action.

A similar observation was reported by
Shani et al. (6). They found that the sand
rat, whose natural diet is high in manganese,
developed an insulin-resistant diabetes when
fed a commercial rat feed containing rela
tively low levels of manganese. The diabetic
condition was reversed after reintroduction
of the manganese-rich natural diet.

Everson and Shrader (7) reported that
guinea pigs, born to manganese-deficient
dams and fed manganese-deficient diets
from birth to 60 days of age, had abnormal
glucose tolerance curves. Histological exami
nation of the pancreas from these animals
indicated that the deficient animals had
hypertrophied pancreatic islet tissue with
degranulated beta-cells and an increased pro
portion of alpha-cells(8). All of these signs o
manganese deficiency were reversed follow
ing dietary manganese supplementation fo
2 months.

Based on the latter observations, we formulated
the hypothesis that manganese deficiency
might result in altered insulin secretion.
Such an abnormality could explain, at
least partially, the altered glucose metabolism
observed in manganese-deficient animals.
The specific effect of manganese on insulin
metabolism might occur at several
levels, including reduced synthesis and/or
secretion of insulin (in addition to reduced
peripheral insulin sensitivity). In this study,
we have examined the relationship of manganese
deficiency and pancreatic function in rats.

This post has been edited by rwac: Sep 28 2009, 03:02 AM

[Lufega]

I read this before. Remembered after reading the part about the Sand rats. Makes you think about the treatment approach to diabetes. Glucose levels are so high that the body is exhausted of all its vitamins and minerals. Simple replenishing some of these lost nutrients, restores a bit of homeostasis.

[Lufega]

Hyaluronic acid through a new injectable nerve guide delivery system enhances peripheral nerve regeneration in the rat.

Seckel BR, Jones D, Hekimian KJ, Wang KK, Chakalis DP, Costas PD.

Department of Plastic and Reconstructive Surgery, Lahey Clinic, Burlington, Massachusetts 01805, USA.
The use of non-neural conduits to bridge gaps in peripheral nerves has been noted in the literature for many years. A logical extension of this concept is the introduction of neurotrophic or growth promoting factors into the lumen. We present here an injectable nerve guide that allows percutaneous access to the microenvironment of the regenerating peripheral nerve within the guide's lumen. Hyaluronic acid, a compound associated with decreased scarring and improved fibrin matrix formation, is added sequentially to the regenerating peripheral rat sciatic nerve via this injectable nerve guide. Assessment of nerve regeneration and reinnervation shows better conduction velocity, higher axon counts, and a trend toward earlier myelination with hyaluronic acid compared with saline. This work not only implies hyaluronic acid's role as an agent that aids nerve growth but also describes a new tool that allows percutaneous access to the milieu of a regenerating nerve.

So, HA aids nerve growth? Cool.

[rwac]

Another thing about Manganese.

It seems like even taking 5mg has a significant effect.
But the 2.5mg in my multi-mineral (NOW-amino acid chelate) doesn't seem to have any effect at all.

It's probably not well absorbed.

[Lufega]

Another thing about Manganese.

It seems like even taking 5mg has a significant effect.
But the 2.5mg in my multi-mineral (NOW-amino acid chelate) doesn't seem to have any effect at all.

It's probably not well absorbed.

You split the tab into quarters? This is good news though. I think you'll feel much safer taking the lower doses long term, if it continues to work. I do not use any multi's for that reason..

[Lufega]

Boom! I can finally explain all of my signs and symptoms (except the alpha 1 antitrypsin deficiency) in terms of dysautonomia (autonomic neuropathy)...

Looks like I spoke too soon.

Heart rate variability reflects severity of COPD in PiZ alpha1-antitrypsin deficiency.

Stein PK, Nelson P, Rottman JN, Howard D, Ward SM, Kleiger RE, Senior RM.
Division of Cardiology, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, MO 63110, USA.

BACKGROUND: Analysis of heart rate variability (HRV) is a powerful method of assessing severity of conditions affecting the autonomic nervous system. STUDY OBJECTIVE: To determine if HRV is decreased and if HRV reflects severity in COPD. DESIGN: Prospective determination of HRV from 24-h outpatient Holter recordings.PATIENTS: Eighteen individuals with PiZ alpha1-antitrypsin deficiency: 13 with COPD and 5 with normal FEV1. HRV was also determined in 18 matched normal control subjects. Approximately 3 years after the initial recording, all COPD subjects were contacted to determine current status. MEASUREMENTS: Indexes of heart rate (HR) and HRV were compared for groups of patients with and without COPD and their control subjects. RESULTS: Mean and minimum HRs were higher in COPD patients. Virtually all indexes of HRV were significantly decreased in COPD patients. No differences were found in HR or HRV between PiZ individuals with normal FEV1 and their age-and gender-matched control subjects. Patients who had a change in status (ie, death, lung transplant, listed for transplant) had significantly higher daytime HRs, lower values for HRV indexes reflecting mixed sympathetic and parasympathetic modulation of HR, and reduced daytime high-frequency spectral power, an index of cardiac vagal modulation. Significant correlations (r=0.48 to 0.88) were found between FEV1 and these and other indexes of HRV. Most other indexes of HRV also tended to be lower for the group whose status had changed. CONCLUSION: PiZ alpha1-antitrypsin deficiency COPD is associated with abnormal cardiac autonomic modulation. Indexes of HRV appear to reflect severity and may have prognostic value in COPD patients.

This post has been edited by Lufega: Sep 28 2009, 03:44 AM

[Lufega]

Role of nitric oxide in the regulation of activity of proteinase inhibitors alpha(1)-antitrypsin and alpha(2)-macroglobulin by capsaicin-sensitive nerves.

Spiridonov VK, Tolochko ZS.
Laboratory of Functional Neuromorphology, Institute of Physiology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk, Russia. spiridon@iph.ma.nsc.ru
Regulation of activity of serine proteinase inhibitor a1-antitrypsin and nonspecific proteinase inhibitor alpha(2)-macroglobulin in the blood by nitric oxide was studied in intact rats and animals with damage to capsaicin-sensitive nerves. Nonselective nitric oxide synthase inhibitor L-NAME produced a dose-dependent increase in alpha(1)-antitrypsin activity in intact animals. Neuronal NO synthase inhibitor 7-nitroindazole increased alpha(2)-macroglobulin activity. Deafferentation with capsaicin was followed by a decrease in alpha(1)-antitrypsin activity. Both inhibitors of nitric oxide synthase increased activity of alpha(1)-antitrypsin in capsaicin-receiving rats. Nitric oxide precursor L-arginine had a normalizing effect on reduced activity of alpha(1)-antitrypsin after capsaicin deafferentation. Our results suggest that nitric oxide has a modulatory effect on activity of proteinase inhibitors and is involved in the effector influence of capsaicin-sensitive nerves on alpha(1)-antitrypsin activity.

I've used capsaicin before. This could have complicated things. Arginine is also needed to remove ammonia from the body. My ammonia levels are a bit on the high side (outside upper range) Using arginine might be worth a try. I have a old bottle of arginine/ornithine. I'll start using it ASAP.

This post has been edited by Lufega: Sep 28 2009, 01:15 PM

[Lufega]

methylselenocysteine upregulates the production of alpha-1-antitrypsin. The abstract doesn't specify the dose, though. So in my arsenal, I have methylselenocysteine, arginine (and manganese as a cofactor), and glisodin. Also the effect glisodin has is minimal but it probably targets part of the problem.

Growth and hepatospecific gene expression of human hepatoma cells in a defined medium.

Darlington GJ, Kelly JH, Buffone GJ.

The production of albumin, alpha-fetoprotein (AFP), and alpha-1 antitrypsin has been compared among human hepatoma cells cultured in medium containing serum, medium containing hormones and growth factors, and a basal medium containing selenium as the only supplement. Growth is sustained in all three media, and the expression of all three proteins was maintained for over 4 mo. in the various media. However, the quantitative production of albumin and AFP were dramatically different in the three media. Two hormones, insulin and triiodothyronine, influenced the level of secreted proteins. Triiodothyronine increases the amount of secreted albumin whereas insulin at 10 micrograms/ml reduced the level of total secreted protein.

Dietary supplementation with selenomethylselenocysteine produces a differential proteomic response.

Mahn AV, Toledo HM, Ruz M.
Department of Chemical Engineering, University of Santiago of Chile, Santiago, Chile. amahn_2000@yahoo.es

Organic forms of selenium offer important health benefits including cancer prevention. Selenium intake has been traditionally quantified as glutathioneperoxidase activity or selenium concentration in blood or tissues. However, these indexes do not reflect organic selenium intake. Effect of dietary supplementation of rats with selenomethylselenocysteine on the blood plasma proteome was investigated in order to detect protein abundance differences between experimental (supranutritional selenium supplementation) and control [minimum selenium dose and sodium selenate instead of selenomethylselenocysteine (SeMSeCys)] groups. Four experimental groups and six control groups consisting of six rats each were fed with base diet supplemented with SeMSeCys or sodium selenate in different concentrations for different periods of time. A proteomic approach, comprising two-dimensional gel electrophoresis and mass spectrometry, was used to assess protein abundance in blood plasma. Statistically significant differences in the abundance of some proteins were detected in all the experimental groups. Four proteins were found to increase their abundance in response to the experimental conditions: apolipoprotein E, haptoglobin and alpha-1-antitrypsin abundance was related to the extent of supplementation period and transthyretin in response to SeMSeCys dose. Apolipoprotein E and transthyretin were not differentially expressed when diets were supplemented with sodium selenate instead of SeMSeCys. We postulate that these proteins are potential biomarkers of chemoprotective selenium intake.

Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.

Kelly E, Greene CM, Carroll TP, McElvaney NG, O'Neill SJ.
Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with emphysematous lung disease and also with liver disease. The liver disease of AAT deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a selenoprotein that, through a chaperone activity, decreases ER stress. To determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured activity of the grp78 promoter and levels of active ATF6 as markers of the unfolded protein response in HepG2 cells transfected with the mutant form of AAT, a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER overload response. To determine the effect of selenium supplementation on the function of SEPS1, we investigated glutathione peroxidase activity, grp78 promoter activity, and NFkappaB activity in the presence or absence of selenium. SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78 promoter and NFkappaB activity, and this effect was enhanced in the presence of selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation.

This post has been edited by Lufega: Sep 28 2009, 02:57 PM

[rwac]

I've been taking 200mcg selenomethylselenocysteine for a while now, because I definitely feel worse if I stop. None of the other forms of selenium seem to work.

I suppose one of these proteins is the explanation ?
Do I possibly have an alpha-1-antitrypsin deficiency which I fixed without knowing about it.

[Lufega]

I've been taking 200mcg selenomethylselenocysteine for a while now, because I definitely feel worse if I stop. None of the other forms of selenium seem to work.

I suppose one of these proteins is the explanation ?
Do I possibly have an alpha-1-antitrypsin deficiency which I fixed without knowing about it.

The only way to know is by getting lab work done. Also, I only read the abstract so I don't know what dose is needed to up-regulate production of these proteins. Either way, I have some handy

[Lufega]

I´ve been thinking a lot lately about calorie restriction and intermittent fasting and it´s relationship to increased autophagy. This study shows that this might also help increase alpha 1 antitrypsin production by hepatocytes.

[quote]Chaperone-mediated regulation of hepatic protein secretion by caloric restriction.
Dhahbi JM, Cao SX, Tillman JB, Mote PL, Madore M, Walford RL, Spindler SR.

Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.

Calorie restriction (CR) delays age-related physiological changes, reduces cancer incidence, and increases maximum life span in mammals. Here we show that CR decreased the expression of many hepatic molecular chaperones and concomitantly increased the rate and efficiency of serum protein secretion. Hepatocytes from calorie-restricted mice secreted twice as much albumin, 63% more alpha1-antitrypsin, and 250% more of the 31.5-kDa protein 2 h after their synthesis. A number of trivial explanations for these results, such as differential rates of protein synthesis and cell leakage during the assay, were eliminated. These novel results suggest that CR may promote the secretion of serum proteins, thereby promoting serum protein turnover. This may reduce the circulating level of damaging, glycoxidated serum proteins. Copyright 2001 Academic Press./quote]

Question is, would adding two fasting days a week, say Tuesday and Thursday, have this same effect??

[Lufega]

Added 3 grams of Arginine and found that is reduces my hand tremors. That was a nice surprise. Seems like Arginine has some effects of the GABA.

L-arginine potentiates GABA-mediated synaptic transmission by a nitric oxide-independent mechanism in rat dopamine neurons.

Shen KZ, Cox BA, Johnson SW.
Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97201, U.S.A.

Effects of L-arginine in the nervous system are often attributed to nitric oxide. Using whole-cell patch pipettes to record membrane currents in voltage-clamp from dopamine neurons in the rat midbrain slice, the present studies found that L-arginine potentiates GABA-dependent membrane currents via a nitric oxide-independent mechanism. L-Arginine (0.3-10 mM) increased the peak amplitude, half-width duration and time constant of decay of GABA(B) receptor-mediated inhibitory postsynaptic currents in a concentration-dependent manner. In the presence of CGP 35348 (300 microM), a GABA(B) receptor antagonist, L-arginine also prolonged the duration of inhibitory postsynaptic currents mediated by GABA(A) receptors, but their amplitudes were reduced. L-Arginine (10 mM) also evoked 17+/-3 pA of outward current (at -60 mV) which was significantly increased in the presence of exogenous GABA (100 microM). Pressure-ejection of GABA from micropipettes produced outward currents mediated by GABA(B) receptors (recorded in bicuculline) or GABA(A) receptors (recorded in CGP 35348); both types of receptor-mediated currents were increased by L-arginine (10 mM). In contrast, outward currents evoked by baclofen, a GABA(B) receptor agonist, were not potentiated by L-arginine. The GABA transport inhibitors NO 711 (1 microM) and nipecotic acid (1 mM) significantly increased the half-width duration and time-constant of decay of GABA(B)-mediated inhibitory postsynaptic currents, thus mimicking effects of L-arginine. However, nitric oxide donors failed to mimic effects of L-arginine on GABA(B) inhibitory postsynaptic currents, and inhibitors of nitric oxide synthesis failed to selectively block the action of L-arginine. These findings suggest that L-arginine potentiates GABA synaptic transmission by a nitric oxide-independent mechanism. Similarities between effects of L-arginine, NO 711 and nipecotic acid suggest that L-arginine inhibits a GABA transporter.

[Lufega]

Started my first day of fast. I was originally going to do 32 hours but instead, I had breakfast this morning. This fast will last until breakfast tomorrow (24 hours). Only supplements I used this morning were lithium and olive leaf.

[Lufega]

Started my first day of fast. I was originally going to do 32 hours but instead, I had breakfast this morning. This fast will last until breakfast tomorrow (24 hours). Only supplements I used this morning were lithium and olive leaf.

I could only go up to 3 pm without food. I really felt HORRIBLE. I'll try it again tomorrow.

[nameless]

If you felt terrible just going to 3 PM, why do you think an entire day will be better? Do you eat a lot of carbs or glucose? I noticed that people who eat high carb, sugary diets tend to feel sickly if they go more than 2-4 hrs without food.

Maybe go for mild CR instead of fasting? I found eating low calorie pretty easy myself... seems I inadvertently do mild CR without even knowing it (until I added up calories).

This post has been edited by nameless: Oct 7 2009, 03:46 AM

[rwac]

If you felt terrible just going to 3 PM, why do you think an entire day will be better? Do you eat a lot of carbs or glucose? I noticed that people who eat high carb, sugary diets tend to feel sickly if they go more than 2-4 hrs without food.

That's definitely one possibility.

The other possibility is that Autophagy is releasing bacteria hiding out in lysosomes into the blood stream.
Borrelia hides out in within lysosomes, where it's protected from the immune system...

[czukles]

I've posted this in cnorwood's thread, but in case you haven't picked up on it, it appears that other forms of lithium should be used in place of lithium orotate.

[Googlebot]

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