Chromium Oligopeptide Activates Insulin Receptor Tyrosine Kinase Activity

A possible new mechanism for the amplification of insulin receptor tyrosine kinase activity in response to insulin has been identified.

The chromium-containing oligopeptide low molecular weight chromium-binding substance (LMWCr) does not effect the tyrosine protein kinase activity of rat adipocytic membrane fragments in the absence of insulin; however, insulin-stimulated kinase activity in the membrane fragments is increased up to 8-fold by the oligopeptide.

Using isolated rat insulin receptor, LMWCr has been shown to bind to insulin-activated insulin receptor with a dissociation constant of circa 250 pM, resulting in the increase of its tyrosine protein kinase activity.

The ability of LMWCr to stimulate insulin receptor tyrosine kinase activity is dependent on its chromium content. The results appear to explain the previously poorly understood relationship between chromium and adult-onset diabetes and cardiovascular disease.

Tyrosine Kinase : Mouse Study Suggests Type 2 Diabetes Potential Treatment

THURSDAY, Dec. 17 (HealthDay News) -- Researchers in Brazil have found that the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor PD153035 improves insulin sensitivity and glucose tolerance in mice fed on a high-fat diet, and may offer a treatment approach for type 2 diabetes, according to a study in the December issue of Diabetes.

Patricia O. Prada, of the State University of Campinas in Brazil, and colleagues put mice on a high-fat diet for eight weeks, then administered PD153035 by tube to the mice for two weeks. They conducted glucose tolerance tests and insulin tolerance tests, as well as tests for biomarkers of inflammation.

The researchers found that treatment with PD153035 for a single day reduced the protein expression of inducible nitric oxide synthase, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, pointing to a reduction of the proinflammatory state in the adipose tissue macrophages. With two weeks of continued treatment, the mice exhibited a marked improvement in glucose tolerance, as well as improved insulin signaling and reduced insulin resistance.


What is PD153035?
PD153035 is reported to be a specific and potent inhibitor of the epidermal growth factor (EGF) receptor tyrosine kinase and, to a lesser degree, of the closely related HER2/neu receptor. We show that PD153035 inhibits EGF-dependent EGF receptor phosphorylation and suppresses the proliferation and clonogenicity of a wide panel of EGF receptor-overexpressing human cancer cell lines.

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein. Tyrosine kinases are a subgroup of the larger class of protein kinases. Phosphorylation of proteins by kinases is an important mechanism in signal transduction for regulation of enzyme activity.

EGF receptor autophosphorylation in response to exogenous EGF was completely inhibited at PD153035 concentrations of >75 nM in cells overexpressing the EGF receptor. In contrast, PD153035 only reduced heregulin-dependent tyrosine phosphorylation in HER2/neu-overexpressing cell lines at significantly higher concentrations (1400-2800 nM). PD153035 exposure did not affect the expression of either EGF receptors or HER2/neu.

PD153035 caused a dose-dependent growth inhibition of EGF receptor-overexpressing cell lines at low micromolar concentrations, and the IC50 in monolayer cultures was less than 1 microM in most cell lines tested. At doses of up to 2.5 microM, the IC50 for HER2/neu-overexpressing cells was not reached. In colony-forming assays, the PD153035 growth-inhibitory activity in cultures driven by endogenous (autocrine) ligand was correlated with EGF receptor number, with higher activity in cells expressing higher numbers of EGF receptors and only minimal activity in cells expressing normal numbers of EGF receptors but high HER2/neu levels.

PD153053 also abolished all growth effects mediated by the addition of exogenous EGF; this condition could be reversed upon removal of the compound. Cotreatment with C225, an anti-EGF receptor-blocking monoclonal antibody, further enhanced the antitumor activity of PD153035, suggesting mechanisms of action for C225 other than competition with ligand binding. This latter finding also suggests that combined anti-EGF receptor strategies may be of enhanced benefit against tumors with high levels of EGF receptor expression.

Chromium and Vanadium for Diabetics

Vanadium is a curious trace element and somewhat difficult to write about. It is a little known trace mineral which seems to be required by the body in relatively tiny amounts, and it is not even clear that it is absolutely necessary at all. But there is nevertheless increasing excitement about its potential therapeutic value. Low blood levels of vanadium have been associated with increases in cholesterol and blood sugar, and it is also believed by some researchers that the mineral may play a role in maintaining the vital balance between sodium and potassium in cells. These characteristics of vanadium have led to speculation that it may act as a protector against heart disease, cancer and especially diabetes.

The idea that vanadium may be of benefit in the battle against diabetes is of relatively recent origin, the first animal research findings only coming to light in the 1980s. But it has been the cause of great excitement. Initial findings suggested that vanadium could control artificially induced diabetes in animals, but orthodox medical opinion remains cautious about the applicability of this research to humans. Some nutritional therapists and practitioners, however, have rushed to embrace vanadium's potential, insisting that high dose vanadium supplements can reduce levels of fasting blood sugar, as well as those of low density lipids (LDLs), the so-called "bad cholesterol" which is strongly associated with atherosclerosis (hardening of the arteries).

Advocates of vanadium therapy also maintain that the mineral can reduce the need for extra insulin in both Type 1 and Type 2 (late onset) diabetes. The problem, however, is that it is difficult to obtain a high intake of vanadium from food alone, and that the mineral in supplement form appears to be relatively poorly absorbed by the body. Moreover, there is evidence that the very high doses required to obtain the therapeutic effects sought may bring unwelcome and potentially serious side effects in their wake; including kidney problems.

This is perhaps not so surprising when it is considered that whilst a fairly typical diet might provide perhaps 50 mcg of vanadium daily, the suggested supplementary doses may be as much as 100 mg; that is 2,000 times the normal daily intake. Whilst potentially beneficial, such doses represent a considerable shock to the system and it is therefore strongly recommended that they be undertaken only under qualified supervision.

Here we have more powerful proof that the trace elements provide a natural cure for diabetes - and many other diseases. In this article, chromium supplementation has been found to provide dramatic improvement - up to and including freedom from all symptoms - in diabetes. However, in another direction of research initiated by Prof. John McNeill at UBC, the trace element vanadium had been found to provide just as dramatic improvements (see "MIRACLE METAL" in "References").

This proves and underscores my assertion that not only one or two trace elements, but the complete natural range of the 72+ trace elements is needed for our naturally robust health. Of course, neither chromium nor vanadium are recognized by our modern agriculture, and are therefore either severely deficient or absent in agricultural soils, hence in all of their products, and hence again, in practically all of our daily food. And as asserted here in these pages, a daily serving of seafood is a natural source of the complete range of the 72+ trace elements, and will provide not only the same, but far, far better results than either chromium or vanadium alone.

The positive effects of vanadium at first appeared promising. Vanadium can improve sensitivity to insulin in both Type I and Type 2 diabetes. It has been shown in human studies to have some ability to lower cholesterol levels and blood pressure. Areas of the world where vanadium (and selenium) levels are high in the soil have lower rates of heart disease. After oral intake, effects of the mineral are seen weeks to months later due to its accumulation in tissues like the kidneys and bone.

Vanadium has been shown to lower growth of human prostate cancer cells in tissue cultures, and to reduce bone cancer and liver cancer in animals. These widespread effects on cancer and diabetes, along with the protective effect seen with another trace mineral, selenium, on certain cancers, suggest that trace minerals are likely to come under more scrutiny for potential health benefits and toxicity.

Unfortunately, vanadium's effects are not all positive. Vanadium works by blocking dozens of enzymes, including ribonucleases, mutases, kinases, and synthases. This indiscriminate blocking action has the potential to be both positive and negative.

Dr. Alavattam Sreedhara originally at Indian Institute of Technology, Mumbai, India, and now at Ohio State University has been doing research on vanadium1,2,3 for several years. He and fellow researchers have discovered several disturbing effects form vanadium, including damage to DNA, blocking of protein synthesis, as well as oxidation of lipids, which is considered a primary step in the development of cardiovascular disease.

But as ever, all of these minerals of course work at optimal effectiveness in the presence of adequate amounts of all the nutrients required by the body; and are best taken as part of a comprehensive multi-vitamin and multi-mineral supplement regime.

GTF Can protect Our Liver

Prof Dr Frank Mao once again worked with his research in depth with his partner. From their research that made great strides the trivalent chromium can protect body from liver damage.

GTF Chromium serves as aliver protective agent againts cholestasis-related liver damage because:
1. Chromium consist of anti-oxidative capacity taht can reduce liver damage
2. Chromium helps to reduce inflammation and thus avoid complications of inflammation to the liver
3. Chromium improve the function of liver and help to regain a healthy liver

National Chung Hsing University Professor Mao Jiahong Jiate Fu biotechnology companies with the industry-academia cooperation, after 12 years of experimental results and found that milk protein binding of chromium and lactoferrin, can effectively control blood sugar, reduce insulin resistance pre-inflammatory factor and generation, and to blood glucose to enter cells, where a large number of fast, better energy metabolism, help to improve high blood sugar problems.

There are many people in China suffering from high blood sugar, however, the National Chung Hsing University Professor Mao Jiahong milk chromium was found inside the blood sugar can increase the role of cellular signals, and can control high blood sugar problems, provides a new adjustment.

Professor Mao Jiahong National Chung Hsing University, said most of the high blood sugar because of diet, stress and lifestyle factors caused, which led to an increase the body's inflammatory factors, insulin resistance, and high blood sugar regulating undesirable phenomenon, therefore, by chromium from the milk can not only reduce the inflammation factor, increasing the sensitivity of cells to allow glucose in patients with high blood sugar be effectively controlled, while also making them feel the spirit and energy to improve.

In addition, this study has also been in last year's "Diabetes, obesity, metabolism" (Diabetes, Obesity, Metabolism) internationally renowned medical journal.

source : www.gtf.com.tw