References 1
1 Eyre H, Kahn R, Robertson RM, and the ACS ADA AHA Collaborative Writing Committee Preventing cancer, cardiovascular disease, and diabetes a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Stroke 2004 35 1999-2010. 2 Coughlin SS, Calle EE, Teras LR, Petrelli J, Thun MJ Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 2004 159 1160-1167. 3 Stattin P, Bjor O, Ferrari P, et al...
Role of Glucose Transporters for the Development of Cancer
Cancer cells require a steady source of metabolic energy in order to continue their uncontrolled growth and proliferation. Accelerated glycolysis is one of the biochemical characteristics of cancer cells. Recent work indicates that glucose transport and metabolism are essential for the post-treatment survival of tumor cells, leading to poor prognosis 46 . Glycolytic breakdown of glucose is preceded by the transport of glucose across the cell membrane, a rate-limiting process mediated by...
Metabolic Syndrome and Risk of Prostate Cancer
Currently, there is a debate whether MeS predicts the incidence of prostate cancer. The hypothesis was tested using the 27-year follow-up of the prospective cohort of the Oslo Study in 1972-1973. MeS was found to predict prostate cancer during 27 years of follow-up, indicating an association between insulin resistance and the incidence of prostate cancer 33 . Features of the MeS, specifically abdominal obesity and hypertension, are also associated with prostate cancer in African-American men 34...
The Cascade of Inflammatory Signaling
Inflammation is the physiological response to biological, mechanical, or chemical stressors. In people with diabetes, increased risk of cardiovascular disease, kidney disease, peripheral vascular disease, autoimmune disorders, obesity, and cancer as well as neurological disorders like Alzheimer's and Parkinson's disease are triggered at least in part from the inflammatory signaling that is chronically upregulated. The inflammatory state is closely related to obesity and insulin resistance, yet...
Evolutionary Consequences of Hypoxia and Acidosis
Recognition of the reliable development of hypoxia in premalignant lesions has allowed the Warburg effect to be derived from modeling of cancer populations in terms of Darwinian selection 21, 25 . It is proposed that aerobic glycolysis arises through two evolutionary steps and represents a critical development in the transition from in situ to invasive cancer. The first evolutionary step is adoption of upregulated glycolysis as a result of fixed or cyclical hypoxia. This transition is observed...
w Essential Fatty Acids
w-3 fatty acids are a group of polyunsaturated fatty acids including a-linolenic acid, eicosapentaenoic acid EPA , and docosahexaenoic acid DHA that come from food sources or dietary supplements. Food sources include fish and fish oils including salmon, rainbow trout, mackerel, krill, anchovy, and sardines , flaxseed oil, berries such as lingonberry and black raspberry , walnuts, and wheat germ. However, w-3 sources that are not from fish require conversion in the body and are therefore not a...
References Vqv
1 DeBeardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB The biology of cancer metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008 7 11-20. 2 Semenza Gl HIF-1 mediates the Warburg effect in clear cell renal carcinoma. J Bioenerg Biomembr 2007 39 231-234. 3 Derevianko A, D'Amico R, Graeber T, Keeping H, Simms HH Endogenous PMN-derived reactive oxygen intermediates provide feedback regulation on respiratory burst signal transduction. J Leukoc Biol 1997 62 268-276. 4...
Recent Advances in Imaging of Insulinoma and pCell Hyperplasia
Current imaging techniques for the detection of insulinomas in patients with hyperin-sulinemic hypoglycemia include endosonography, which is considered the most sensitive imaging technique, followed by MRI or CT. Somatostatin receptor scintigraphy SRS is a valuable imaging technique in most neuroendocrine tumors of the gastrointestinal tract. In the case of benign insulinomas, however, its value is limited due to the fact that many insulinomas do not express the somatostatin receptor subtypes...
References
1 Smyth S, Heron A Diabetes and obesity the twin 6 epidemics. Nat Med 2006 12 75-80. 2 Prentki M, Nolan CJ Islet p-cell failure in type 2 diabetes. J Clin Invest 2006 116 1802-1812. 3 Gallwitz B Therapies for the treatment of type 2 7 diabetes mellitus based on incretin action. Minerva Endocrinol 2006 31 133-147. 4 Creutzfeldt W The incretin concept today. Diabeto-logia 1979 16 75-85. 8 5 Nauck MA, et al Preserved incretin activity of glucagon-like peptide 1 7-36 amide but not of 9 synthetic...
Incretin Mimetics
Exenatide and Its Pharmacological Profile In 1992, exendin-4, a peptide with a 52 amino acid sequence similarity to GLP-1, was isolated from the salivary gland of the lizard Heloderma suspectum Gila monster . Exendin-4 acts as a high potency agonist at the GLP-1 receptor on p cells and the fragment exendin 9-39 is a high potency antagonist 14 . Synthetic recombinant exendin-4 was named exenatide. Exenatide shares all effects of native GLP-1. Figure 4 shows the amino acid sequences of GLP-1,...
DPP and DPP Inhibitors
DPP-4 is a ubiquitous enzyme that can be detected in the endothelium of different organs and that is measurable as circulating enzymatic activity in plasma. Besides GLP-1 and GIP, additional peptides, such as pituitary adenylate cyclase-activating polypeptide PACAP and gastrin-releasing peptide, are substrates of DPP-4 table 2 . However, the affinity of DPP-4 is higher toward GLP-1 than towards other peptides including GIP. DPP-4 cleaves and inactivates GLP-1 within a few minutes 9 . For this...
Diabetes Mellitus and Breast Cancer Risk
Different strategies were used in order to assess the association between diabetes mellitus and breast cancer risk. We divided these studies into three categories 1 studies that evaluated the association between diabetes and breast cancer risk 2 studies that evaluated the association between diabetes and breast cancer mortality, and 3 studies of the association between blood levels of insulin resistance markers, such as glucose or insulin and breast cancer risk. Diabetes Mellitus and Breast...
Carcinogenesis Reconsidered
In healthy tissue, constraints to tumorigenesis exist in the form of hard-wired barriers that prevent disruption of tissue architecture and function by inappropriate cellular proliferation. These controls include highly-regulated activation by specific pro-growth signals and growth-inhibitory barriers through anoikis see below and interactions with other cells and the extracellualr matrix 15-18 . Classical theoretical models focus on these normal tissue controls and propose that carcinogenesis...
Glucose Metabolism Oxidative Phosphorylation versus Aerobe Glycolysis
However, even once glucose has entered the cell, its fate is not the same when normal tissue is compared to malignant cells. Glucose in healthy cells will be metabolized via the glycolytic pathway until pyruvate see fig. 1, highlighted in light blue , which will be converted into acetyl-CoA, replenishing the concomitant tricarboxylic acid cycle TCA see fig. 1, highlighted in green . The resulting NADH H and FADH2 will further be used in the mitochondrial respiratory chain to recycle ATP from...
References Huh
1 Garcia SB, Novelli M, Wright NA The clonal origin and clonal evolution of epithelial tumors. Int J Exp Pathol 2000 81 89-116. 2 Nowell PC The clonal evolution of tumor cell populations. Science 1976 194 23-28. 3 Ilyas M, Straub J, Tomlinson IP, Bodmer WF Genetic pathways in colorectal and other cancers. Eur J Cancer 1999 35 335-351. 4 Fearon ER, Vogelstein B A genetic model for col-orectal tumorigenesis. Cell 1990 61 759-767. 5 Gatenby RA, Gillies RJ A microenvironmental model of...
Bitter Melon Momordica charantia
Bitter melon M. charantia is a green, bitter vegetable from the gourd family, grown in tropical and subtropical regions throughout the Amazon, East Africa, Asia, the Caribbean, and South America. The slender, climbing vine produces a warty, oblong gourd resembling a small cucumber. Bitter melon is known by many names which include wild cucumber, bitter gourd, balsam apple, balsam pear, ampalaya Philippines , and Kerala India . Clinical conditions for which bitter melon extracts primarily from...
K Masur Witten F Thevenod Witten KS Znker Witten
17 figures, 11 in color, and 2 tables, 2008 Basel Freiburg Paris London New York Bangalore Bangkok Shanghai Singapore Tokyo Sydney Founded 1981 by F. Belfiore, Catania Institute of Immunology and Experimental Oncology University of Witten Herdecke Witten, Germany University of Witten Herdecke Witten, Germany Department of Physiology and Pathophysiology Institute of Immunology and Experimental Oncology University of Witten Herdecke Witten, Germany Library of Congress Cataloging-in-Publication...
Vitamin D
Vitamin D is needed to maintain adequate blood levels of insulin. Vitamin D deficiency has been shown to impair insulin synthesis and secretion in humans and in animal models of diabetes. Vitamin D deficiency predisposes individuals to type 1 and type 2 diabetes, and receptors for its activated form - 1a,25-dihydroxyvitamin D3 -have been identified in both 3-cells and immune cells. Serum 25-hydroxyvitamin D levels have been reported to be inversely related to body mass index and body fat...
Acknowledgement
I thank Prof. Patrik Rorsman Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK for his continuous interest in my work. 1 Zimmet P, Alberti KG, Shaw J Global and societal implications of the diabetes epidemic. Nature 2001 414 782-787. 2 Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Carling D, Kahn BB Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002 415 339-343. 3 Hotamisligil GS The role of TNF-a and TNF...
Abstract 1
A reliable method for repeated non-invasive quantification of P-cell mass in vivo in humans will enhance our understanding of the pathophysiology of both type 1 and type 2 diabetes. Individual patients with type 2 diabetes show large differences regarding the relative contribution of insulin resistance or insulin deficiency to the diabetic state. Also, the deterioration of P-cell function varies. When P -cell mass could be measured in vivo in humans, the effects of different diabetes treatments...
Failed Adaptation to Insulin Resistance and pCell Failure The Natural History
Normal pancreatic p-cell responds to a chronic fuel excess and obesity-associated insulin resistance with compensatory insulin hypersecretion in order to maintain nor-moglycemia. This adaptive response to insulin resistance involves changes in both function and mass, and is so efficient that normal glucose tolerance is maintained. Longitudinal studies of subjects that develop T2D show a rise in insulin levels in the normoglycemic and prediabetes phases that keep glycemia near normal despite the...
aLipoic Acid
a-Lipoic acid, also known as lipoic acid LA or thioctic acid, and its reduced form, dihydrolipoic acid, are powerful antioxidants. LA scavenges hydroxyl radicals, hypochlorous acid, peroxynitrite, and singlet oxygen. Dihydrolipoic acid also scavenges superoxide and peroxyl radicals and can regenerate thioredoxin, vitamin C, and glutathione, which in turn can recycle vitamin E. There are several possible sources of oxidative stress in diabetes including glycation reactions,...
Info 1
ncreased sex hormone production Reduced SHBG production ncreased sex hormone production Reduced SHBG production Increased plasma estrogen, testosterone Increased plasma estrogen, testosterone Increased proliferation, invasiveness, angiogenesis Reduced apoptosis Fig. 2. Mechanisms associating type 2 diabetes and breast cancer. Insulin resistance leads to high plasma insulin concentrations, which activate the extracellular-related-kinase ERK and the AKT pathways through activation of the insulin...
References Mjc
1 Willett WC Balancing lifestyle and genomics research for disease prevention. Science 2002 296 695-698. 2 Novo G, Corrado E, Muratori I, Tantillo R, Bellia A, Galluzzo A, Vitale G, Novo S Markers of inflammation and prevalence of vascular disease in patients with metabolic syndrome. Int Angiol 2007 26 312-317. 3 De Luca C, Olefsky JM Inflammation and insulin resistance. FEBS Lett 2008 582 97-105. 4 Keri RA, Ho SM, Hunt PA, Knudsen KE, Soto AM, Prins GS An evaluation of evidence for the...