Treating insulin resistant diabetes,reversing diabetes by dr julian whitaker 883,pw electroplaters - Easy Way


Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder affecting approximately 7 per cent of women of reproductive age. In the majority of cases PCOS is diagnosed because amenorrhea, obesity or overweight, acne or hirsutism occur. The most common characteristic is the menstrual abnormality: menstrual intervals can be longer than 35 days and there are fewer than eight menstrual cycles a year. The elevated levels of male hormones result in excess facial and body hair (hirsutism) and adult or severe adolescent acne. In these women the ovaries appear polycystic so characterized by an increase in antral follicles and ovarian stroma as well as by theca cell hyperplasia and ovarian cortical thickening.
Therefore, expecially if the obesity (or the overweight) increases the condition, PCOS becomes a factor and a part of an heterogeneous disorder called "metabolic syndrome", in which the metabolism of carbohydrates and the pathway of insulin play a very significant role.
Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal obesity, elevated blood pressure, elevated plasma glucose, high serum triglycerides, and low high-density cholesterol (HDL) levels. Insulin resistance is defined clinically as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization in an individual as much as it does in a normal population.
Insuline resistance is very common and plays a central pathogenic role in PCOS, it is present in approximately 50-70 per cent of these women.
The studies about insulin signaling pathways in different responsive tissues - such as adipose tissues, skeletal muscles, adipose tissues, fibroblasts as well as ovaries - suggest a post receptor signaling defect: metabolic action of insulin is compromised but not the steroidogenic and mitogenic actions. For these reasons in the women affected by PCOS high androgen levels lead to menstrual disturbances, development of ovarian cysts and hirsutism, all clear symtomps typical of the disorder. IR also increases the risk for development of glucose intolerance, type 2 diabetes mellitus, hypertension, dyslipidaemia and cardiovascular abnormalities in these women. Adipocytes are not simply a storage depot: they are also endocrine organs, with multiple metabolic roles.
The adipocyte hormones leptin and adiponectin activate the AMP-activated protein kinase (AMPK) in muscle and other tissues, a pathway that increases fat oxidation and glucose transport.
Also physical exercise activates the AMPK and, importantly, the same pathway is activated by the antidiabetic agents such as thiazolidinediones and metformin, used in the therapy of PCOS. When fat mass increases, leptin blood level increases, suppressing appetite until weight is lost. However obese individuals generally exhibit an unusually high circulating concentration of leptin : they are resistant to the effects of leptin.
Also adiponectin is synthetised by adipocytes and its plasma concentration falls with increasing obesity.
Finally adipose tissue in obese persons shows higher expression of pro-inflammatory proteins, including TNF-? and IL-6. TNF-? increases systemic insulin resistance by promoting the release of fatty acids from adipose tissue.
In the same condition IL-6(whose concentration correlates with insulin resistance) increases lipolysis and fat oxidation.
Moreover, there is a relationship between iron deficiency and obesity: in fact the chronic low-grade inflammation that characterizes obesity enhances hepcidin production, the principal regulator of iron availability. Then, hepcidin inhibits iron transport across the gut mucosa reducing iron absorption and also inhibits transport of iron out of macrophages (site of iron storage and transport). A considerable iron deficiency ends up paralysing mechanisms and pathways that need iron, first of all the mitochondrial elecron transport chain that drives ATP synthesis.
About the last two points it is funded by now that the two major pharmacological approaches to the treatment of diabetes are also an efficient therapy of PCOS. These are the insulin sensitizers: the biguanide metformin and the thiazolidinediones troglitazone, pioglitazone, and rosiglitazone. Metformin modestly increases menstrual regularity and ovulation and decreases weight and hyperandrogenism.
If drugs are not enough to avoid a pregnancy, gonadotropins so follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are administered by injection. However, the safest and cheapest therapy that has shown benefit both in diabetes and PCOS is weight loss by lifestyle modification. Several studies have revealed that even modest weight loss (10–20%) improves all symptoms of PCOS in obese patients: acne, hirsutism, and menstrual irregularities. The improvements are likely a result of the reductions in insulin levels, insulin resistance, dyslipidaemia and hypertension (all factors of the metabolic syndrome). It is useful to pay attention to dietary composition: increasing fiber intake (because fiber slows nutrient absorption after meals and reduces insulin secretion), reducing both carbohydrates and the total calories intake. Finally, as a lifestyle modification, physical exercise helps sustain weight loss, but it also has other benefits. Exercise as the primary intervention without attendant weight loss (< 5% weight loss) improved insulin sensitivity and testosterone index and induced ovulation in 9 of 18 obese PCOS patients.
The key enzyme of all the therapies is certainly the 5' AMP-activated protein kinase or AMPK that plays a central role in cellular energy homeostasis.
It is expressed in various tissues, including the liver, the brain, and the skeletal muscle. Then, clearly the AMPK pathway involves all the targets implied in the more difficult complications of PCOS, so the metabolic syndrome and the insuline resistance. Both the drug therapy, first of all the metformin, and the muscle contraction close in the activation of this enzyme, that is also the target of leptin and adiponectin.
The PCOS is a very heterogeneous disorder that needs an early diagnosis to avoid the regression in the worse manifestations, such as the diseases related with the carbohydrates metabolism and the insulin resistance. Either way there are valid solutions and treatments for both women who want to plan a pregnancy, and not. Anyway, the most prudent and natural approach to this disorder corresponds to adjust the lifestyle with a correct and adapt diet and above all an healthy and moderate physical exercise.
If you are battling insulin resistance then you should take steps immediately to reverse insulin resistance with your diet.
And insulin resistance, which may have far- reaching clinical implications as a cause of unregulated tissue growth, may also respond to an ancestral diet.


Significant increase in the thermo stability of enzymes is observed by adding disulfide bonds. In the wild type (native) T4 lysozyme, there are two cysteine residues which however are not held together by a disulfide bond. Introduction of disulfide bonds increases the folded structure and thermo stability of the enzyme. At high temperature, the amino acids asparagine and also glutamine are likely to undergo deamidation (releasing ammonia) to respectively form aspartic acid and glutamic acid. This is a dimeric enzyme with identical subunits, each one having two asparagine residues which are thermo-sensitive (undergo deamidation).
Sometimes, the presence of free sulfhydryl groups (contributed by cysteine residues) in more numbers may be responsible for the low activity of the protein. Some of the recombinant proteins can be improved in their stability and biology activity by a second generation variants. By replacing methionine at by valine, an oxidative-resistant variant of ?1-antitrypsin has been created (Fig. Tissue plasminogen activator is therapeutically used to lyse the blood clots that cause myocardial infarction. The enzyme dihydrofolate reductase (DHFR) catalyses the conversion of 7, 8-dihydrofolate to 5, 6, 7, 8-tetrahydrofolate. Replacement of glycine by any other amino acid in the protein structure, in general, decreases the stability. It is possible to improve the functional activities of enzymes, by improving their kinetic properties (Km, specificity etc.) through oligonucleotide- directed mutagenesis. Subtilisin is a major industrial enzyme secreted by Gram-positive bacteria (Bacillus species).
The reason being that methionine lying close to the active site gets oxidized, making the enzyme inactive. Subtilisin is an enzyme that has been extensively exploited for genetic manipulations over the past 15 years. The nucleotide sequence in the DNA encoding for the amino acids that bind to calcium is removed.
This is an enzyme used in the control of leukemia (uncontrolled growth of white blood cells). Replacement of threonine by either alanine or proline, variants of tyrosyl t-RNA synthetase have been produced.
The protein engineering studies can be successfully employed for modifying enzyme specificities. By using protein engineering technique, the existing restriction endonucleases have been suitably modified to produce rare cutters. The recent development in protein engineering is DNA shuffling, also known as molecular breeding (developed by Nesse in 2000). Although with limited success, chemical modifications of proteins have been attempted to increase the stability of proteins to high temperature and organic solvents. Selected examples of protein engineering are described above only to highlight the scope of protein engineering. Metabolic syndrome increases the risk of developing cardiovascular disease, particularly heart failure, and diabetes. IR progresses towards the development of compensatory hyperinsulinemia, and hyperinsulinemia implies hyperandrogenemia. The enlarged adipocytes of obese individuals recruit macrophages and promote inflammation and the release of a range of factors that predispose toward insulin resistance. This hormone circulates in blood and acts on receptors in the hypothalamus of the brain, where it inhibits appetite counteracting the effects of neuropeptide Y (that on the contrary stimulates the appetite) and supporting the synthesis of ?-MSH, an appetite suppressant.
The high concentrations of leptin from the enlarged adipocytes drives leptin desensitization, so the body does not adequately receive the satiety feeling subsequent to eating. Reduced adiponectin concentrations correlate with insulin resistance, hyperinsulinemia and hypertrophy of the adipocytes.
So, in states of high hepcidin levels (including inflammatory states such as the obesity), serum iron levels fall. In particular is known that the cytochrome complex, or cyt c is a small heme protein associated with the inner mithocondrial membrane that transfers electrons between Complexes III (Coenzyme Q - Cyt C reductase) and IV (Cyt C oxidase) through the passage from the ferric iron (oxidized form) to ferrous iron (reduced form). These agents improve not only glucose control, but also the reproductive abnormalities associated with PCOS.
It improves insulin resistance, increases peripheral glucose uptake and decreases hepatic glucose production. Pramlintide is an analog of amylin, a ?-cell hormone that is normally co-secreted with insulin; it complements the effects of insulin in postprandial glucose control, in part by suppressing glucagon secretion. Moreover an outpatient surgery called “laparoscopic ovarian drilling” is an option for few candidate women with PCOS. In PCOS, women who self-reported 8 hours of sports activities per week had improvement in acne and menstrual irregularities.
The functions of AMPK are: stimulation of hepatic fatty acid oxidation, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells. Diabetes is a condition that results when insulin, a hormone, is unable to perform its tasks. The popular South Beach Diet and the Zone Diet are healthy diets for people who have insulin resistance or metabolic syndrome. Read about insulin resistance is causes, symptoms, treatment (like diet), risk factors and more. The insulin resistance diet is not all that hard to follow and it just may reverse your condition and restore your long-term health.
Die neue Begrifflichkeit beschreibt eine Kostform, die postprandiale Blut- zucker- und Insulinspitzen verhindern hilft. However, the additional disulfide bonds should not interfere with the normal enzyme function.


By oligonucleotide-directed mutagenesis, cysteine residues created disulfide bonds between positions (numbered form N-terminal end) 3 and 97, 9 and 164, and 21 and 142 of the enzyme. These alterations are often associated with changes in the protein folding and loss of biological activity. Oligo­nucleotide-directed mutagenesis was used to introduce threonine or isoleucine in place of asparagine.
In such a case, the protein or enzyme stability and its activity can be increased by reducing the number of sulfhydryl groups.
By introducing single amino acid substitutions, insulin’s were found to be in monomeric state with good stability and biological activity.
The latter coenzyme is closely involved in one carbon metabolism, which ultimately results in the synthesis of nucleic acids and amino acids. It is a serine protease very widely used as an enzyme detergent (cleaning agent in laundries).
The result is that about 50% of the native amino acids of this enzyme have been changed by in vitro mutagenesis.
Intravenous administration of asparaginase cleaves asparagine to aspartate (the reduced availability of asparagine restricts cell proliferation).
This is what has been achieved in oligonucleotide-directed mutagenesis with respect to restriction endonucleases. As such, there are two types of restriction endonucleases—the frequent cutters which recognize a sequence of 4-6 bp and rare cutters recognizing a sequence above 8 bp. If the iron level is very low the cyt c and all the chain may not to operate well and the muscle prefer not to oxidize energetic substrates, principally the glucose. Anti-androgen therapy, such as spironolactone (that blocks the effects of androgens on the skin) can be added for further treatment of hirsutism. D-chiro-inositol is an insulin sensitizer that has preliminarily been shown to increase ovulation in PCOS.
The surgeon makes a small incision in the abdomen, inserts a tube attached to a camera (laparoscope) and uses electrical or laser energy to burn holes in follicles on the surface of the ovaries.
People with insulin resistance should choose their food carefully as it can have an impact on their condition. In general, the new protein with added disulfide bonds does not readily unfold at high temperatures, and further it is resistant to denaturation at non-physiological conditions (high pH, presence of organic solvents). This was done by changing two, four or six amino acids (in close proximity) to cysteine residues to respectively form one, two or three disulfide bonds.
Introduction of disulfide bonds (one, two or three) makes it thermo-stable, and substantially improves its functional efficiency.
This new enzyme is particularly important in treating patients with genetic deficiency of ?1,-antitrypsin.
By replacing asparagine residue with glutamine, the half-lite of tPA can be substantially increased. The inhibition of DHFR (conventionally by folate analogues such as methotrexate) will restrict the growth of tumor cells.
In T4 lysozyme, substitution of glycine by alanine, and alanine by pro-line are found to increase the enzyme stability. However, the large scale industrial use of native subtilisin is restricted due to the oxidative inactivation of this enzyme. This has been done, and in fact, all the 19 other amino acids have been tried as substitutes for methionine, with varying success.
In fact, success has been achieved in creating calcium-free subtilisin with good stability and activity.
Surprisingly, the asparaginases from different sources exhibited differences in their effectiveness to control leukemia. The technique primarily involves isolation of genes from each species, and then creation of hybrids in different combinations.
By using glutaraldehyde, certain proteins (hemoglobin, insulin, phosphofructokinase, lactate dehydrogenase) have been stabilized. In this way it may become not responsive to insuline (because it doesn’t manage to use glucose) and aids the condition of insuline resistance. These characteristics are particularly important for industrial applications of certain enzymes.
On the other hand, when the asparagine residues were replaced by aspartic acid, the enzyme was unstable even at low temperature, with reduced activity. In fact, the cysteine residues were involved in intermolecular disulfide bonding resulting in the formation of dimers and oligomers. It may be noted that the structures of these two amino acids are similar except that serine has oxygen in place of sulfur in cysteine. The free methionine is oxidized to methionine sulfoxide, making ?1-antitrypsin a poor inhibitor of elastase. This is due to the fact that glutamine is less glycosylated than asparagine and this makes a difference in the half-life of tPA.
However, since most of these enzymes recognize the same sequence on the DNA for their action, there are only about 200 different recognition sites.
While applying this approach to subtilisin, genes from 26 species were mixed to create a library. By employing site-directed mutagenesis, replacement of glycine by alanine was found to produce DHFR which is completely inactive.
By the above process, IFN ? with increased stability and good biological activity can be produced. Increased stability is in fact required for storage and therapeutic use of proteins such as interferon’s.




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