Hyperthermia-induced Hsp90·eNOS Preserves Mitochondrial Respiration in Hyperglycemic EC by Down-regulating Glut-1 and Up-regulating G6PD Activity

'the present study provides a novel mechanism wherein the reduced oxidative stress in heat-shocked hyperglycemic cells down-regulates Glut-1 and glucose uptake, and fine-tuning of this pathway may be a potential approach to use for therapeutic benefit of diabetes mellitus."

Presley, T., Vedam, K., Druhan, L. J. & Ilangovan, G. Hyperthermia-induced Hsp90·eNOS Preserves Mitochondrial Respiration in Hyperglycemic Endothelial Cells by Down-regulating Glut-1 and Up-regulating G6PD Activity. Journal of Biological Chemistry 285, 38194-38203 (2010). URL http://dx.doi.org/10.1074/jbc.M110.147728.  http://www.citeulike.org/user/HEIRS/article/8399736

HEIRS Library Tags: Hsp90

Strengthening Link Between FOXO1 and Inflammation, Insulin Resistance.

Comment: Past studies show EGCG connection. (Reiter)

"Researchers at the University of California, San Diego School of Medicine have discovered that a multi-tasking protein called FoxO1 has another important but previously unknown function: It directly interacts with macrophages, promoting an inflammatory response that can lead to insulin resistance and diabetes."


Macrophage Protein Has Major Role In Inflammation:

Related Tag: FOXO1
Supplemental Citation:
Reiter, Chad E. N., Kim, Jeong-a, and Quon, Michael J. (2010). Green Tea Polyphenol Epigallocatechin Gallate Reduces Endothelin-1 Expression and Secretion in Vascular Endothelial Cells: Roles for AMP-Activated Protein Kinase, Akt, and FOXO1. Endocrinology, 151(1):103-114.
http://www.citeulike.org/user/HEIRS/article/6087895

Insulin B:9-23/IFA immunisation induces Tregs that control late-stage prediabetes in NOD mice through IL-10 and IFNgamma.

CiteULike: Subcutaneous insulin B:9-23/IFA immunisation induces Tregs that control late-stage prediabetes in NOD mice through IL-10 and IFNgamma.: "Fousteri, G., Dave, A., Bot, A., Juntti, T., Omid, S., and von Herrath, M. (2010). Subcutaneous insulin b:9-23/ifa immunisation induces tregs that control late-stage prediabetes in nod mice through il-10 and ifngamma. Diabetologia, 53(9):1958-1970."

Oxidative stress and inflammation modulate peroxisome proliferator-activated receptors with regional discrepancy in diabetic heart.

"Diabetes can modulate PPARs through increased inflammatory cytokines and oxidative stress, which are attenuated by ascorbate treatment."

CiteULike: Oxidative stress and inflammation modulate peroxisome proliferator-activated receptors with regional discrepancy in diabetic heart.:

Mouse Study Sheds Light on Diabetes-Heart Disease Link

"high blood sugar elevates reactive molecules that contain the oxygen atom (called reactive oxygen species) in autonomic neurons. This chemical change inactivates the neurotransmitter receptors at these synapses, they noted." Mouse Study Sheds Light on Diabetes-Heart Disease Link:

New Evidence That Drinking Coffee May Reduce The Risk Of Diabetes

"Scientists are reporting new evidence that drinking coffee may help prevent diabetes and that caffeine may be the ingredient largely responsible for this effect. Their findings, among the first animal studies to demonstrate this apparent link, appear in ACS' bi-weekly Journal of Agricultural and Food Chemistry."

New Evidence That Drinking Coffee May Reduce The Risk Of Diabetes:

Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the Nrf2-Keap1 defense pathway.

"We hypothesize that diminished Nrf2/ARE activity contributes to increased oxidative stress and mitochondrial dysfunction in the vasculature leading to endothelial dysfunction, insulin resistance and abnormal angiogenesis observed in diabetes"

CiteULike: Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the Nrf2-Keap1 defense pathway.:

Study Links Heptachlor, PCBs and Form of Vitamin E to Diabetes

"An analysis of 266 potential environmental contributors to type 2 diabetes published May 20, 2010 in the online edition of the journal PLoS ONE, links the disease to individuals who have higher levels of polychlorinated biphenyls (PCBs) and the pesticide heptachlor, as well a form of vitamin E found at high levels in soybean and corn oil, in their bodies compared to the general population. PCB was banned in 1979 and most uses of heptachlor were canceled between 1978 and 1989 (except for limited control of fire ants, which continues), but the compounds persist in the environment, especially near former industrial sites or contaminated soil"

Beyond Pesticides Daily News Blog » Blog Archive » Study Links Heptachlor, PCBs and Form of Vitamin E to Diabetes:

PTSD may raise diabetes risk in service members

It's possible that the stress response associated with PTSD could contribute to widespread inflammation in the body and lower sensitivity to the blood-sugar-regulating hormone insulin, which could lead to diabetes, researchers say.

PTSD may raise diabetes risk in service members Reuters: "PTSD may raise diabetes risk in service members"

Impairments in Muscle Function After Cigarette Exposure and Environmental Illness

PGC-1a a protein factor necessary for mitochondrial function and may be reduced with exposure to LPS as well as, from impairments in Nrf2. This study demonstrates that TNF-a (already identified as a factor in CFS and Parkinson's) is generated from exposure to cigarette smoke (and lots of other environmental contaminants) and has been shown to down-regulate PGC-1a that may lead to vascular and myocyte dysfunction. PGC-1a also regulates a number of glucose transporters such as GLUT1 and GLUT4 which trasport glucose into cells.  When one looks at a condition related to glucose uptake from impairment of glucose transporters such as in GLUT1 deficiency, there are recognizable patterns of impairment one may recognize in other environmental illnesses including CFS and fibromyalgia and also described as Parkinsonism and ataxia-like symptoms.  Because Nrf2 contributes to PGC-1a expression, a deficiency in Nrf2 may also present with these types of symptoms impaired after cigarette exposure and particulate matter from diesel exhaust. Of course, other factors such as accumulation of ammonia and genetic SNP may also pose potential cellular threats. PGC-1a can be increased through exercise but this will be dependant on the availabity of NRF1 (another protein) regulated by Nrf2/HO-1. Sauna and Waon therapy have been shown to elevate PGC-1a and Nrf2. Deficiencies of PGC-1a may exacerbate the autoimmune-type presentation of environmental illness in Nrf2 deficiencies which produce less HO-1. Lack of PGC-1a and Nrf2 may contribute to the development of chronic diabetes in addition to other metabolic complications and numerous other conditions, such as cardiovascular disease.


For review:

• Chemical Sensitivity and Th2 Autoimmune Disease: The Loss of Treg Cells As Referee!
• Immunosuppression in Environmental Illness By High Fat and Cytokines: Ameliorated By Green Tea Compound!?
• Nrf2 Expression Is Regulated by Epigenetic Mechanisms in Prostate Cancer
• T Regulatory Cells and Vitamin D - Their Importance to Environmental Illness Including Chemical Sensitivity.

CiteULike: TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure.: "Tang, K., Wagner, P. D., and Breen, E. C. (2010). Tnf-alpha-mediated reduction in pgc-1alpha may impair skeletal muscle function after cigarette smoke exposure. Journal of cellular physiology, 222(2):320-327."





Lihua CHE, N. and Chiwai WON, G. Estrogen-related receptor a inverse agonist enhances basal glucose uptake in myotubes through reactive oxygen species. Biological Pharmacology Bulletin, 32(7):1199-1203. http://www.citeulike.org/user/HEIRS/article/6512026
Arany, Z., Foo, S.-Y. Y., Ma, Y., Ruas, J. L., Bommi-Reddy, A., Girnun, G., Cooper, M., Laznik, D., Chinsomboon, J., Rangwala, S. M., Baek, K. H. H., Rosenzweig, A., and Spiegelman, B. M. (2008). Hif-independent regulation of vegf and angiogenesis by the transcriptional coactivator pgc-1alpha. Nature, 451(7181):1008-1012. http://www.citeulike.org/user/HEIRS/article/2406298
Pons, R., Collins, A., Rotstein, M., Engelstad, K., and De Vivo, D. C. (2009). The spectrum of movement disorders in glut-1 deficiency. Movement Disorders, 9999(9999):NA+. http://www.citeulike.org/user/HEIRS/article/6512017
Piantadosi, C. A., Carraway, M. S., Babiker, A., and Suliman, H. B. (2008). Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via nrf2-mediated transcriptional control of nuclear respiratory factor-1. Circ Res, 103(11):1232-1240. http://www.citeulike.org/user/HEIRS/article/4617070?show_msg=already_posted
Glucose Transporter. Wipedia. Retrieved January 10, 2009.

Adequate Regulation of G6PD Levels May Help Treat Diabetes.

"Researchers identified a protein (G6PD protein) and its antioxidant product (NAPDH) that both prevent the death and promote the growth of cells which produce and release insulin in the pancreas (beta cells)."

Link

Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity.

Summary: Exercise training restored in vivo mitochondrial function in T2D. Insulin mediated glucose disposal and metabolic flexibility improved in T2D in the face of near significantly increased IMCL content. This indicates that increased capacity to store IMCL and restoration of improved mitochondrial function contribute to improved muscle insulin sensitivity.


Meex, R. C., Schrauwen-Hinderling, V. B., Moonen-Kornips, E., Schaart, G., Mensink, M., Phielix, E., van de Weijer, T., Sels, J.-P. P., Schrauwen, P., and Hesselink, M. K. (2009). Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity. Diabetes. http://www.citeulike.org/user/HEIRS/article/6440076



Gazelle Edge

Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity

Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity: "URL: Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity

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Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat

Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat: "URL: Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat

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Adhd: A diabetic hyperglycemic dilemma.

Henley, D. E. and Glatthaar, C. (2004). Adhd: A diabetic hyperglycemic dilemma. Diabetes Care, 27(12):3020-3021. http://www.citeulike.org/user/HEIRS/article/6345974



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Mitochondrial defects ‘drive beta-cell dysfunction in diabetes’

Dysfunction of the pancreatic beta cells – the primary defect underlying insulin resistance and Type 2 diabetes – is driven by abnormal mitochondrial function and morphology, Canadian researchers have discovered.

LINK

Environmental endocrine disruptors promote adipogenesis in the 3t3-l1 cell line through glucocorticoid receptor activation.

Summary: EDCs are able to promote adipogenesis through the activation of the GR, further implicating these compounds in the rising rates of obesity and diabetes.

Sargis, R. M., Johnson, D. N., Choudhury, R. A., and Brady, M. J. (2009). Environmental endocrine disruptors promote adipogenesis in the 3t3-l1 cell line through glucocorticoid receptor activation. Obesity. http://www.citeulike.org/user/HEIRS/article/6198203

A common ucp2 polymorphism predisposes to stress hyperglycaemia in severe sepsis.

Summary: "A common, functional polymorphism in the promoter region of the UCP2 gene is associated with hyperglycaemia and insulin resistance in severe sepsis."

Pyle, A., Ibbett, I. M., Gordon, C., Keers, S. M., Walker, M., Chinnery, P. F., and Baudouin, S. V. (2009). A common ucp2 polymorphism predisposes to stress hyperglycaemia in severe sepsis. J Med Genet, 46(11):773-775. http://www.citeulike.org/user/HEIRS/article/6056691

Inflammation and Alterations in Fat Cells By Pesticide Alterations of Anti-inflammatory Protein Genes!

Background: Some experts believe that changes in gene expression may be a consequence of certain chemical exposures. Researchers are now focusing a lot of attention on the effects of these exposures on adipocytes which can produce inflammatory chemokines which may generate inflammation.  It has been observed that some types of exposures are associated with obesity which is a risk factor for diabetes while, others can lead to weight reduction.   Arsenescu demonstrated toxic exposures can stimulate and increase expansion of adipose tissue and other studies show alterations in the process of differentiation of preadipoctyes into adipocytes. In 2008, a preliminary study suggested endothelial dysfunction contributes to fat cell development because adipose stromal cells are in close contact with endothelial cells of capillaries and small blood vessels. (ScienceDaily) Long-term high serum levels of dioxin has been shown to contribute to endothelial dysfunction which provides a possible mechanism for the association of certain exposures to endothelial dysfunction, obesity and a higher risk for diabetes. (Peclova)

In the past, obesity has been characterized by differentiation of preadipocytes to adipocytes and involves the coordinated responses of a number of proteins with fatty acids that leads to increases of the size of fat cells.(Uto-Kondo) However, a recent study suggests that in in the case of abdominal obesity which may have more severe long-term health effects, there is impairment of the ability for preadipocytes to differentiate into adipocytes. Irakson says that "inhibition of this type can lead to a proinflammatory state and macrophage-like phenotype and as Hou explains "elevated levels of TNF-a or Il-1b in inflammatory tissues prolongs the survival of these immune cells and lengthens the durations they remain in an inflammatory state." 

 In one study, eldrin causes inhibition of a binding protein and interfered with expression of the anti-inflammatory protein PPAR-gamma and altered the expression of NF-kappaB which usually decreases as adipocytes differentiate. (Moreno-Aliego) We have suggested that the aberrant signaling from the AhR, which normally is important for cellular homeostasis and contributes to detoxification of PAHs and HAHS, may be an important factor in MCS. Hanlon et el notes that activation of the AhR by dioxin blocks hormone-induced adipocyte differentiation through the suppression of PPAR-gamma. The presence of inflammatory mediators are also associated with insulin resistance which can further impair normal cell function and reductions in the expression of Nrf2 may further complicate it. Chronic inflammation have been suggested as a causal factor in environmental illnesses including obesity and diabetes. One study shows proteins associated with cell death are less efficient in diffentiated adipocytes than in undifferentiated cells when introduced to a reactive species stimulus. Kojima confirmed an increase in antioxidants including MnSOD, catalase, Cu/ZnSOD as well as, FOXO with the the progression of adipocyte differentiation.  From this study, it has been concluded that ROS-generated apoptosis is associated with the expression of FOXO3a in undifferentiated adipocytes and FOXO expression suppresses ROS-apoptosis through activation of scavenging enzymes in differentiated ones. With this study in mind and considering that uncontrolled production of ROS contribute to cellular processes that cause inflammation, preventing differentiation of adipocytes may have negative consequences in certain cases.

Kojima, T., Norose, T., Tsuchiya, K., and Sakamoto, K. Mouse 3t3-l1 cells acquire resistance against oxidative stress as the adipocytes differentiate via the transcription factor foxo. Apoptosis. http://www.citeulike.org/user/HEIRS/article/5998696
Isakson, P., Hammarstedt, A., Gustafson, B., and Smith, U. (2009). Impaired preadipocyte differentiation in human abdominal obesity. Diabetes, 58(7):1550-1557. http://www.citeulike.org/user/HEIRS/article/5017576
Hou, F. F., Boyce, J., Zhang, Y., and Owen, W. F. (2000). Phenotypic and functional characteristics of macrophage-like cells differentiated in pro-inflammatory cytokine-containing cultures. Immunology and cell biology, 78(3):205-213. http://www.citeulike.org/user/HEIRS/article/5998701
Hanlon, P. (2003). Ahr- and erk-dependent pathways function synergistically to mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin suppression of peroxisome proliferator-activated receptor-γ1 expression and subsequent adipocyte differentiation. Toxicology and Applied Pharmacology, 189(1):11-27. http://www.citeulike.org/user/HEIRS/article/5778106
Moreno-Aliaga, M. J. and Matsumura, F. (1999). Endrin inhibits adipocyte differentiation by selectively altering expression pattern of ccaat/enhancer binding protein-alpha in 3t3-l1 cells. Mol Pharmacol, 56(1):91-101. http://www.citeulike.org/user/HEIRS/article/5998840
Uto-Kondo, H., Ohmori, R., Kiyose, C., Kishimoto, Y., Saito, H., Igarashi, O., and Kondo, K. (2009). Tocotrienol suppresses adipocyte differentiation and akt phosphorylation in 3t3-l1 preadipocytes. J. Nutr., 139(1):51-57. http://www.citeulike.org/user/HEIRS/article/5998926
Healthy Blood Vessels May Prevent Fat Growth. ScienceDaily. September 23, 2008.
Pelclová, D., Prázny, M., Skrha, J., Fenclová, Z., Kalousová, M., Urban, P., Navrátil, T., Senholdová, Z., and Smerhovsky, Z. (2007). 2,3,7,8-tcdd exposure, endothelial dysfunction and impaired microvascular reactivity. Human & experimental toxicology, 26(9):705-713. http://www.citeulike.org/group/7254/article/6000451

Phytochemicals Help To Reduce Oxidative Stress, Inflammation,Obesity and Diabetes

"The cheeseburger and French fries might look tempting, but eating a serving of broccoli or leafy greens first could help people battle metabolic processes that lead to obesity and heart disease, a new University of Florida study shows." Click here.