One focuses of my research is on the genetic of exceptional longevity, where we hypothesize and demonstrated that centenarians have protective genes, which allows the delay of aging or for the protection against age-related diseases. In a Program I am leading we take full advantage of phenotypes, DNA, whole exome sequencing to all subjects and cells from the Ashkenazi Jewish families with exceptional longevity and the appropriate controls I have established at Einstein (over 2800 samples of which ~670 are centenarians) and discovered underling genomic differences associated with longevity. Longevity Genes Project (LGP) is a cross-sectional, on-going collection of blood and phenotype from families with centenarian proband. LonGenity is a longitudinal study of ~1100 subjects, half offspring of parents with exceptional longevity, validating and following their aging in relationship to their genome. Another focus of my research is on the biology and molecular physiology leading to the metabolic decline of aging, and we hypothesize that the brain leads this decline. My lab has identified several central pathways that specifically alter body fat distribution and insulin action and secretion by intraventricular or hypothalamic administration of several peptides that are modulated by aging including: leptin, IGF-1, IGFBP3 and resveratrol. I am a PI of TAME (targeting Aging with MEtformin) and of the Administrative core (AC). I conceived TAME, partnered with Drs. Espeland and Kritchevsky and together formed EC partnerships that drove TAME to its current stage. Bringing my expertise in biology, metformin and molecular physiology and in human trials my role in this program is to lead the Executive Committee to set the overall operational priorities for the study, lead the Steering Committee (SC) and define their agenda, develop sub-committee charges, monitor the progress and operations of all study subcommittees, set and monitor study timelines and progress towards goals and recommend corrective action when necessary, monitor TAME’s budget and reallocate financial resources as necessary, assure field center quality and compliance with federal regulations regarding the responsible conduct of research, review safety reports and manage communications with the central IRB and the DSMB. I will also be in charge of coordinating external support for TAME through AFAR activities, ensure the support that they have pledged so far, including supporting preliminary studies, leading the progress with the FDA and assure funding by other NIH institutes. In addition I will engage with Dr. Kunchel investigators beyond the TAME study team to expand the science of TAME and to provide a resource to accelerate the pace of geroscience I will also co-chair the Scientific Advisory Board with Dr. Krichevsky.
Dr. Barzilai is a chaired Professor of Medicine and Genetics and Director of the biggest Center in the world to study the Biology of Aging. He is the recipient of an NIH Merit Award aiming to extend the healthy life span in rodents by biological interventions. He also studies families of centenarians that have provided genetic/biological insights on the protection against aging. Several drugs are developed based, in part, on these paradigm-changing studies. He is a recipient of numerous prestigious awards, including the recipient of the 2010 Irving S. Wright Award of Distinction in Aging Research and is the 2018 recipient of the IPSEN Longevity award. He is leading the TAME (Targeting/Taming Aging with Metformin) multi central study to prove that concept that multi morbidities of aging can be delayed in humans and change the FDA indications to allow for next generation interventions. He has been featured in major papers, TV program and documentaries and has been Consulting or presented the promise for targeting aging at The Singapore Prime Minister Office, several International Banks, Pepsico, Milkin Institute, The Economist and Wired Magazine
Neither neuropathy, retinopathy, nephropathy, nor excess mortality are prevented by intensive lowering of glucose levels in 34,533 Type 2 diabetic patients (Boussageon et al., 2011). Exposing patients to adverse effects of drugs in absence of demonstrable efficacy is unjustified, yet remains standard therapy. An alternative to the hyperglycemia hypothesis for pathogenesis of diabetic complications is urgently needed. Hypotheses: Insufficient insulin/IGF neurotrophic activities is the dominant cause of diabetic complications; replacement of such activities should ameliorate complications irrespective of unabated hyperglycemia (2, 3). These hypotheses were tested by infusing IGFs, insulin, or their combination into diabetic rats to determine whether complications are alleviated under conditions in which hyperglycemia remains unabated. Diminished IGF mRNA levels are found in peripheral nerves, brain and spinal cord in diabetes. Replacement IGF infusion prevented impaired sensory and motor nerve regeneration, hyperalgesia, abnormal ultrastructure in autonomic axons, loss of epidermal nerve fiber density, and poor gastric wound healing despite unabated hyperglycemia (4-5). A decrease in total mRNA, protein, and DNA levels was associated with brain atrophy and impaired learning/memory in diabetic rats. Insulin and IGF i.c.v. infusion in tiny doses prevented all such disturbances under conditions of unabated hyperglycemia (6-7). Insulin and IGFs are master switches controlling the levels of hundreds of proteins in brain. Loss of protein regulation, not hyperglycemia, is proposed as the main pathogenic cause for diabetic complications. Governments should manufacture clinical grade IGF (off-patent). Clinical trials are urgently needed to test insulin/IGF therapy.
Douglas N. Ishii was born in a US concentration camp at the onset of WWII. B.A. Biochemistry, Univ. Calif. Berkeley; Ph.D. Pharmacology,Stanford Univ. Medical Sch.; postdoctoral fellow Neurobiology, Stanford Univ. He was Associate Prof. Pharmacology at Columbia Univ. NYC, and is a Professor of Biomedical Sciences at Colorado State Univ. He served on scientific study sections for National Science Foundation, National Institutes of Health, and the Juvenile Diabetes International Foundation. Articles on his research on pathogenesis of diabetic complications, and brain atrophy in Alzheimer’s disease, have appeared in Der Spiegel, Hong Kong Standard, NY Times, LA Times, Denver Post, ABC News, Forbes News, and USA Today.
A new systems approach to diseased states and wellness result in a new branch in the healthcare services, namely, Personalized and Precision Medicine (PM). To achieve the implementation of PPM concept into clinical practice (including endocrinology), it is necessary to create a fundamentally new strategy based upon the subclinical recognition of biomarkers to predict, to forecast and to prognosticate long before the disease clinically manifests itself. Each decision-maker values the impact of their decision to use PPM on their own budget and well-being, which may not necessarily be optimal for society as a whole. It would be extremely useful to integrate data harvesting from different databanks for applications such as prediction and personalization of further treatment to thus provide more tailored measures for the patients resulting in improved patient outcomes, reduced adverse events, and more cost effective use of health care resources. A lack of medical guidelines has been identified by the majority of responders as the predominant barrier for adoption, indicating a need for the development of best practices and guidelines to support the implementation of PPM! PPM-taxonomy of diseases that is now beingdeveloped will aid the pursuit of PPM bydefining at the molecular level new diseases and subtypesthat can be treated in a specific way. Using genetic data andother databases, most of chronic disorders (including T1D and T2D) andother diseases will become classified into disease subsets, allwith their own best treatments being tailored. So, PPM Clinics of the Futurewill channel new sources of information assembled into clinicallyfocused data sets and will use the emerging datastreams to deliver individualized treatments (canonical) for patients and/or for persons-at-risk (preventive & prophylactic) withphenotypically similar but molecularlydissimilar diseases.A PPM-based diabetes clinic will provide:(i) geneticinformation and counseling; (ii) a digital phenotypicassessment and counseling based on an extensive set of laboratorytests, sensor information, digital images, and personalizeddata analysis; (iii) sensor-based behavior assessment and lifestylecounseling; and (iv) targeted therapywhere appropriate. Implementation of PPM requires a lot before the current model “physician-patient” could be gradually displaced by a new model “medical advisor-healthy person-at-risk”. This is the reason for developing global scientific, clinical, social, and educational projects in the area of PPM to elicit the content of the new branch.
Sergey Suchkov was born in the City of Astrakhan, Russia, in a family of dynasty medical doctors. In 1980, graduated from Astrakhan State Medical University and was awarded with MD. In 1985, Suchkov maintained his PhD as a PhD student of the I.M. Sechenov Moscow Medical Academy and Institute of Medical Enzymology. In 2001, Suchkov maintained his Doctor Degree at the National Institute of Immunology, Russia. From 1989 through 1995, DrSuchkov was being a Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004 - a Chair of the Dept for Clinical Immunology, Moscow Clinical Research Institute (MONIKI). In 1993-1996, DrSuchkov was a Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK.
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Udaya M Kabadi completed General Medicine residency at KEM Hospital and obtained Post-graduate degree (MD) from Mumbai University, Mumbai, India. Hecontinued his Post-graduate training in Internal Medicine and fellowship training in New York, NY, USA. He is Board Certified in Internal Medicine, Endocrinology,Metabolism and Geriatric Medicine by American Board of Internal Medicine. He is a fellow of American College of Physicians, American College of Endocrinologyand Royal College of Physicians of Canada. He is an Adjunct Professor of Medicine at Des Moines University, Des Moines, Iowa and University of Iowa, Iowa,USA. He has authored over 190 papers in peer reviewed medical journals and 2 books. He has conducted over 500 CME presentations and chaired symposia atregional, national and international meetings. He serves as a member of Editorial Board of many medical journals. He has also been elected 'Teacher of the Year'by undergraduate students and post-graduate trainees on several occasions during his career.
Diabetic neuropathy can be a painful condition that is currently not adequately treated by available medicines. Over 10% of adults in the USA suffer from type 2 diabetes. It is estimated that 50% or more of these patients will experience diabetic neuropathy during the course of their disease.Pain and burning sensations in the legs, arms, hands, feet, lower back and other areas are common symptoms of three types of diabetic neuropathy: peripheral neuropathy, radiculoplexus neuropathy and mononeuropathy. Aspirin, ibuprofen, naproxen, acetaminophen and other NSAIDs are commonly used to treat neuropathy with little success. These dangerous drugs kill over 50,000 people every year from heart attacks, strokes and ulcers. Capsaicin cream is an effective treatment but initially increases pain and burning sensations. A liniment made from California sagebrush (Artemisia californica) is a powerful, rapid treatment for diabetic neuropathy that patients in California can make for themselves for free. Each patient is instructed to begin living a healthy lifestyle in order to minimize the effects of diabetic neuropathy.
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Introduction- Healthcare costsassociated with physical inactivity in the workplace setting arerising. Increased physical activity has been recommended for the prevention of cardiovascular disease; however, there is limited data on the effect of short-term walking on physical health outcomes in the University workforce. The purpose of this study was to evaluate the effects of pedometer-assessed physical activity (10,000 steps•d-1walking goal) for 4-weeks on cardio-metabolic outcomes such as blood pressure, blood glucose levels andlipid profile among the University’s academic faculty and staff. Methods-Thirty-seven (8M/29F, 50±6yrs; body mass index 28.9±5.6 kg/m2) apparently healthy participants who were non-smokers, non-diabetic, free of any known cardiovascular disease, not on antihypertensive or cholesterol medications were recruited from the University workforce. Blood pressure was measured using Omron BP710n instrument. Participants were encouraged to complete a pedometer-based walking intervention (walking step-goal: 10,000 steps•d-1; 5 days•week-1; 4 weeks).Fasting blood glucose and complete lipid profile were analyzed using Cholestech LDX lipid analyzer, before and after intervention. Hip based Omron Pedometer HJ-112 was used to record step-counts. Pedometer settings were personalized based on the participant’s stride length. Participants were instructed to maintain their regular diet during the study period. Results- Baseline vs. post-intervention (Mean±SD) for systolic blood pressure (120.0±13.3 vs. 115.2±12.7 mmHg; p<0.001), diastolic BP (78.4±8.1 vs. 74.0±7.2 mmHg; p<0.0001), low density lipoprotein (121.5±36.5 vs. 110.2±33.4; mg/dL; p=0.020) were statistically significant. Changes in step- counts (9850±2473 vs. 9887±2260), fasting blood glucose, total-cholesterol, triglycerides and high density lipoproteins were not statistically significant. Conclusion- Our preliminary study modestly decreased blood pressure and low density lipoprotein by ~5% & 7%, respectively over the course of four-weeks of walking intervention. This suggests thatphysical activity (10,000 steps•d-1 walking goal) for 4-weeksmoderately improves cardio-metabolic parameters in a relatively healthy cohort at a workplace setting.
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Our OBJECTIVE was to realize a comparative evaluation of the efficacy of rehabilitation programmes, considering the impact of different physical modalities in the prevention and treatment of the clinical continuum: metabolic syndrome –> non-insulino-dependent diabetes mellitus (NIDDM) –> diabetic polyneuropathy (DPNP) –> diabetic foot (DF). MATERIAL and METHODS: We investigate a total of 1170 patients with NIDDM, DPNP (sensorimotor form, distal type) and neuropathic DF; randomized in 10 therapeutic groups; controlled before, during and after the rehabilitation course (of 20 treatment days), and 1 month after. All patients received active physiotherapy, ergotherapy, patient education. Patients of the first group (gr1) were used as a control group (receiving only this treatment). In gr2 we applied too soft tissue techniques (massage, post-isometric relaxation; stretching; tractions & mobilizations). In gr3 a peloidotheraputic procedure was added (sea lye compresses). In patients of next groups (gr 4-10) we applied a pre-formed modality (gr4 - iontophoresis, gr5 – TENS, gr6 - functional electrostimulation-FES, gr7 – interferential currents, gr8 - magnetic field, gr9 - LASER, gr10 - Deep Oscillation-DO). For database management we used t-test (ANOVA) and Wilcoxon signed rank test. The comparative analysis of the RESULTS demonstrates statistically significant beneficial effects on: metabolic patterns, pain, hypopallesthesia, muscle weakness; trophic feet alterations; electroexcitability and electroconductibility of peripheral nerves, quality of life. DISCUSSION: TENS and DO are the better analgesic agents; Laser and Peloidotherapy are effective on trophic alterations; FES is usefull in peripheral paresis. CONCLUSION: The complex rehabilitation programme must be adapted to every concrete DPNP-DF case.
Prof. Ivet Koleva is a medical doctor, specialist in Neurology and in Physical & Rehabilitation Medicine (PRM); with 30+ years of clinical practice. She has completed a PhD thesis on ‘Physical Prevention, Therapy and Rehabilitation of Diabetic Polyneuropathy’; and a thesis for Doctor-es-Medical Sciences on ‘Neurorehabilitation in patients with socially important neurological diseases’. Associate professor (2006) and Professor (2010) in PRM. Author of scientific papers, monographs and manuals in the fields of Rehabilitation, Pain Management, Grasp and Gait Rehabilitation. Borislav Yoshinov is Physiotherapist, actually student in Medicine. Rorislav Yoshinov is student in Information technologies.
Introduction:Over the past few decades, obesity and Diabetes mellitus has become a global health challenge. Multiple epidemiological studies have shown that low testosterone levels are associated with and predict the future development of T2D and the metabolic syndrome. Aim of study: The aim of study was to show the influence of testosterone replacement therapy on BMI, HbA1c level, Diabetic neuropathy,and CV-risk factors - with patient diabetes mellitus and Androgen deficiency. Materials and Methods:125 male patient with diabetes mellitus was screened,85 subjects with 41-65 years and BMI 27,0 – 48,0 kg/m2 were randomized In placebo-controlled study, who underwent a routine physical examination and choose free testosterone examination.Also for assessment of autonomic diabetic neuropathy was used “Vegetotester” — digital instrument for vegetative nervous system study. According to the laboratory and clinical condition we divided patients into two groups. 1) First group treatment group 2) Second group placebo group. In the first group we used diet, physical activity (Lifestyle intervention implies reduced calorie diet (The reduction of daily calorie intake in 800-1200 calorie, it was selected individually), patient’s antidiabetic therapy and testosterone replacement therapy (TRT), (testosterone undecanoate 250 mgr/ml intra- muscular 3 months 1 time). In second group we used diet, physical activity (Lifestyle intervention implies reduced calorie diet (The reduction of daily calorie intake in 800-1200 calorie, it was selected individually), patient’s antidiabetic therapy and placebo. Results: After six months of treatment we repeated the diagnostic assessments: We had some positive results cholesterol, triglyceride and LDL levels decreased, and HDL increased both of group but better results was in first group which was clinically significant. Free testosterone level increased in all groups but the best results was in I group which was clinically significant where was used of testosterone undecanoate. HbA1c decreased in both group but in I group we had the best result. BMI decreased in both groups but more reduction was in I group. leptin level after treatment was approximately same in both groups, but compared best results was achieved in I group, also blood pressure were reduced in both group, where we found alike results. Also in first group was positive results about autonomic diabetic neuropathy. Discussion:Autonomic diabetic neuropathy,Serum testosterone, glycosylated hemoglobin, high-density lipoprotein cholesterol, triglyceride concentrations, and the BMI, Hypertansion improved in both treatment groups after 26 weeks of treatment. We have shown that testosterone replacement therapy improves insulin resistance and glycemic control in hypogonadal men with diabetes. Conclusion:Our study demonstrated that it is possible to break into this vicious circle by raising testosterone levels in diabetic men and low testosterone level. Maybe low level of testosterone has some role in pathogenesis of autonomic diabetic neuropathy. Re-instituting physiological levels of testosterone in hypoandrogenic men as our small study shown, have an important role in reducing the prevalence of diabetic complication.
Objective: To identify circular RNAs (circRNAs) associated with type 2 diabetes mellitus (T2DM) and their clinical significance. Methods: CircRNAs expression profiles of the peripheral blood from six T2DM patients and six healthy individuals were compaired by microarray (Agilent human circRNA Array V2.0) analysis. Bioinformatics analysis were used for selection of circRNAs whose target genes are involved in insulin signaling pathways among the differentially expressed circRNAs (Fold Change >2 and P<0.05). Candidate miRNAs were further validated by quantitative real-time PCR (qRT-PCR) in a large sample including 79 newly dignosed T2DM patients, 68 individuals with impaired fasting glucose (IFG) and 79 healthy controls. The association between circRNA expression and potential risk of T2DM and IFG was assessed by multivariate logistic regression models. The circRNA predictors of insulin resistance (IR) were identified by stepwise multiple regression analysis. The diagnostic performance for T2DM was evaluate by area under the receiver operating characteristic curve (AUC). Results: Three circRNAs, including hsa_circ_0056891 (target genes: CAV1, INSIG1, PIK3R1), hsa_circ_0063425 (target genes: CAV1, INSIG1, PIK3CG, IRS1) and hsa_circ_0071336 (target genes: PIK3R2, AKT1, IRS2, IRS1, PDK1) were selected as candidate miRNAs for validation. Decreasing levels of the three circRNAs were significant independent predictors of T2DM, IFG and IR (P<0.05). These circRNAs significantly correlated with insulin adiponectin and leptin levels (P<0.05). The three-circRNA panel had a high accuracy for diagnosing T2DM (AUC=0.803, 95%CI: 0.719-0.886). Conclusions: hsa_circ_0056891, hsa_circ_0063425, and hsa_circ_0071336 in peripheral blood may be important markers of insulin signaling pathways and may play important roles in the pathogenesis of T2DM and IR.
Yu-Xiang Yan has completed her PhD from Capital Medical University, China. She is a professor of Department of Epidemiology and Biostatistics, School of Public Health, Capital Medical University, Beijing, China. Her research area includes Epidemiology of Chronic Diseases and Molecular Epidemiology. She has published more than 20 papers in reputed journals.
There is confusion amongst people living with Diabetes. Is Wilford Brimley still the face? There are hundreds, if not thousands, of different diabetic organizations (IDF, ADA, Beyond 1, Novo Nordisk, Canadian Diabetes, JDRF, Joslin, Sanofi, NIDDK, National Diabetes Educational Program, American Association of Clinical Endocrinologists) and so on.How many different organizations promote their information and do not communicate with the others, to get the best information to people living with Diabetes? Is it their job to talk to other companies, no.What we have come across is: Non-Profits give benefits to their highest donors, and for-profitspromote their agenda. Each one has its purpose, but the end result is about the diabetic not the business, isn’t it? Endocrinologists and diabetic educators are the primary sources for each person with diabetes to get help and educated to improve one’s life. But, most Endocrinologists are directing from a different sheet of music. If, over 400 million people throughout our world have diabetes, why isn’t there one person (a face) or one organization, leading it? Diabetes is a crisis and needs attention, today. When Ebola broke out a few years ago, attention and money was all over it, which is good! Is diabetes not treated in the same light because it’s a “hidden” disease: meaning, until someone goes blind or gets a limb amputated, the disease isn’t seen. For example, when the blue circle was adopted in 2006 from the United Nations, why is it that most diabetic organizations who adopted it, still use their own logo? Shouldn’t the blue circle be known by the world, just like the pink ribbon for breast cancer? Example, why is one organization promoting high carbohydrate versus another promoting low carbohydrate? Example, why won’t several “diabetic” organizations promote a diabetes awareness music video that was not made by their company? Is it about “their” company or about bringing help? An Awareness brings in education, help and hopefully more government funding, to help find a cure. So, I ask the questions: are we wanting to bring healing, are we wanting to find a cure, and who is leading of diabetesepidemic?
This study investigated the effects of diabetes mellitus on burnout among Walter Sisulu University (WSU) employees as well as the prevalence of diabetes mellitus and burnout. A mixed method research design using quantitative and qualitative approaches was employed in order to explore the effects of diabetes on burnout as well as the prevalence of diabetes and burnout at WSU. A cross-sectional survey was used to gather quantitative data and semi-structured interviews were used for the qualitative data collection. A total number of 169 participants were involved in this study. This included 154 participants and 15 participants who were selected for the quantitative and qualitative respectively using random sampling technique and purposive sampling method. Qualitative data analysis involved coding data and analysing the emerging themes to form the basis of the findings. The quantitative data was analysed using Stata version 13. The study findings indicated that the prevalence of diabetes at WSU is 16% and 57% participants were burned out. It was further found that the majority of participants (58%) who were diabetic also suffered from burnout. The relationship between diabetes and burnout was found to be significant.
CaweNovukela is currentlystudyingtowradsPh.D at Walter Sisulu University and is the Dean of the Faculty of Business Sciences. Dr M J Ntsaba is the Head of Department of Nursing at Walter Sisulu and has several peer reviewed publications and has supervised more than 25 Masters and Ph.D students. Prof S K Mfusi is the Head of Department of Psychology. He has several publications in reputable journals and has supervised more than 20 Masters and PhD students.
Background: Obesity, which is defined as the rate of body fat, was associated with a greater risk for development of chronic kidney disease (CKD) among subjects with and without hypertension, diabetes or cardiovascular disease. We aimed to consider the association between obesity and classified CKD according to both estimated glomerular filtration rate (e-GFR) and albuminuria categories in people with manifested hypertension. Methods: One hundred-two overweight and/or obese subjects with manifested hypertension were enclosed on mean age 72.07 ± 12.3 years old and they matched to thirty hypertensive control subjects with a normal body weight. Our participants were classified in both eGFR and albuminuria categories according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. The obesity was defined by both a high body mass index (BMI ≥ 25 Kg/m2 as overweight and/or ≥ 30 Kg/m2 as obese) and the existence of central obesity by waist circumference (WC) measurement. Results: We observed significant association between BMI classes and classified albuminuria (x2 =20.6, p=0.001). The high WC was significantly associated with classified albuminuria (x2 =18.3, p=0.001) in our high BMI participants and such as finding was also supported by an adjusted model using confounders. The relationship between eGFR categories and both BMI classes and high WC was found non-significant. The classified eGFR was significantly associated with high WC in lean/normal BMI control group (x2 =10.4, p=0.01). Conclusion: Obesity was significantly associated with classified albuminuria rather than classified glomerular filtration rate independently on the existence of hypertension as a comorbidity.
GOAL : Analysis and evaluation of different contraceptive methods used in women with diabetes and comparison to recommendations (WHO and ADA). PATIENTES / METHODS: Cross-sectional descriptive study of 50 diabetic women under contraception. RESULTS: -The tubal ligation (LT) was the most used from 38 years followed by the intrauterine device (IUD). -The different types of hormonal contraceptives used: the estrogen-progestogen microdosed pill, the progestogen micropill and the injectable progestins in 4.5% of the patients each. -All women using hormonal contraception were overweight or obese. -In multiparous women, LT was found with a rate of 59.5% followed by the IUD (43.7%). The IUD was the most used method (28%) in women with type 1 diabetes. -For type 2 diabetics, LT comes first with 30%, followed by the IUD (27%), the hormonal method (22.8%, predominance for progestins). - Patients with older diabetes who have been living for more than 15 years, used the majority (15%) of LT. -66.4% under IUDs had a genital infection. conclusion: The majority of the patients studied follow a contraceptive method adapted to their age, their gestures, their parity, the type, the seniority and the vascular complications of the diabetes. However, weight monitoring, metabolic and gynecological controls should be strengthened especially in cases of hormonal contraception and IUDs.
During the last two decades we have opened a new field of research on oxytocin (OT). The most important findings included discovery of entire OT system, including OT and OT receptor (OTR), in human and rodent hearts and explanation of its role in cardiogenesis and cardioprotection. Recently we investigated the role of OT treatment in diabetic cardiomyopathy on db/db mice model (C57BL/KsJ-db/db). Their lean littermates (db/+) served as control. Our experiments demonstrated for the first time that chronic treatment with OT (125 ng/kg • h) for a period of 12 weeks, significantly reduced the development of cardiomyopathy, obesity and diabetes in db/db mice. OT treatment increased circulating OT levels, significantly reduced serum resistin, body fat accumulation (19%; P < .001), fasting blood glucose levels by (23%; P < .001), and improved glucose tolerance and insulin sensitivity. OT also normalized cardiac OTR, ANP, and BNP, expressions and prevented systolic and diastolic dysfunction as well as cardiomyocyte hypertrophy, fibrosis, and apoptosis. Furthermore, OT reduced cardiac oxidative stress and inflammation and normalized the 5′-adenosine monophosphate-activated protein kinase signaling pathway. The normalization of cardiac structure and function by OT treatment in db/db mice contrasted with only partial improvement of hyperglycemia and hyperinsulinemia. The present study indicates that OT treatment was effective in restoring the cardioprotective OT-NP system and in preventing abnormal cardiac remodelling in the db/db mice. These observations strengthen our hypothesis that normalization of cardiac OT/NP system protects the heart in pathological conditions.
Jolanta Gutkowska is Professor of Medicine at UdeM and Experimental Medicine at McGill University. She is recognized by her works of cardiac hormones and diabetes. The most known her accomplishments include biology of natriuretic peptides and discovery of cardiac oxytocin and its role in cardiovascular system in normal and pathological conditions like heart failure. She is the director of Laboratory of Cardiovascular Biochemistry in Research Center CHUM, Montreal. She has published more than 470 papers and has been serving as a supervisor of numerous MS and PhD students.
Evidence from recent years has demonstrated that the neuropeptide hormone oxytocin (OT) has the capacity to prevent cardiomyopathy in animal models of diabetes and reduces ischemia-reperfusion injury (IR) in animal models. Presently, we investigated molecular mechanism of OT protection in the cardiac cell model of IR, H9c2. I-R was induced in an anoxic chamber for 2 hours and followed by 2 h of reperfusion. In comparison to normoxia, I-R decreased formazan production by H9c2 cells to 63.5 ± 1.7% (MTT assay) and enhanced apoptosis from 1.7 ± 0.3% to 2.8 ± 0.4% (Tunel test). Using these assays we found that treatment with OT (1 to 500 nM) exerted dose-dependent protection during I-R, especially when OT was added at the time of reperfusion. We found that OT directly acts on H9c2 cells to improve their survival during the acute phase of simulated ischemia and reperfusion. OT treatment increases intracellular Ca2+, which corroborates the observation that an elevation in intracellular Ca2+ results in mitochondrial Ca2+ overload and ROS generation. Further findings by confocal microscopy indicated that OT-induced mitochondrial ROS production and eNOS activation may be mediated by OT receptor-linked transactivation of the upstream kinases Akt and ERK1/2 as later indicated by Western blot. The following eNOS phosphorylation resulted in nitric oxide (NO) production. In conclusion: The OTR protected H9c2 cells against I-R, especially if activated at the onset of reperfusion. The OTR-transduced signals include Akt and PKG. These kinases translocate to the mitochondria, where they act in a localized signalosome.
Marek Jankowski is recognized by his work in molecular biology of hormones involved in cardioprotection. The most known his accomplishments include biology of natriuretic peptides, estrogen receptors and molecular biology of oxytocin in cardiovascular system. He is working in Laboratory of Cardiovascular Biochemistry in Research Center CHUM, Montreal. He has published more than 130 papers in reputed journals and has been serving as a supervisor of numerous MS and PhD students.