15^th World Congress on Endocrinology & Diabetes September 20-21, 2019 | Prague, Czech Republic

Biography:

Wei-Chiang Shen is a Professor in Pharmaceutical Sciences at the University Of Southern California School Of Pharmacy. His research interests focus on the development of novel systems for improving peptide and protein drug delivery. He has published more than 150 papers in different areas of biomedical sciences. He is a Co-Author of the textbook “Immunology” for Pharmacy Students and a Co-editor of the book “Antibody-Drug Conjugates – the 21st Century Magic Bullets for Cancer”. He was elected to Fellow of the American Association of Pharmaceutical Scientists in 1992 and Fellow of the American Association for the Advancement of Sciences in 2000

Wei-Chiang Shen is a Professor in Pharmaceutical Sciences at the University Of Southern California School Of Pharmacy. His research interests focus on the development of novel systems for improving peptide and protein drug delivery. He has published more than 150 papers in different areas of biomedical sciences. He is a Co-Author of the textbook “Immunology” for Pharmacy Students and a Co-editor of the book “Antibody-Drug Conjugates – the 21st Century Magic Bullets for Cancer”. He was elected to Fellow of the American Association of Pharmaceutical Scientists in 1992 and Fellow of the American Association for the Advancement of Sciences in 2000

Abstract:

We have recently prepared a recombinant proinsulin-transferrin fusion protein (ProINS-Tf). ProINS-Tf is an inactive form of insulin analog, but can be selectively absorbed, activated, and retained in the liver. We have demonstrated in type 1 diabetes mouse models that ProINS-Tf is a highly liver-targeted and long-lasting insulin prodrug. Due to the binding to both insulin and transferrin receptor, the liver-activated ProINS-Tf exhibited a significantly higher affinity to insulin receptor when compared with the native insulin. The bivalent binding of activated ProINS-Tf induces a longer and stronger activation of insulin receptor as demonstrated in the enhanced and prolonged Akt phosphorylation with hepatoma cells. Furthermore, ProINS-Tf can overcome insulin resistance in palmitate-treated HepG2 cells, as well as in severe hyperglycemic NOD mice. Therefore, ProINS-Tf can potentially be developed into a safe and effective insulin prodrug for the control of basal glycaemia in diabetes and for the treatment/prevention of insulin resistance- associated diseases

Biography:

Ravi Muppirala is a Biophysicist who has held academic appointments at TIFR, Carnegie-Mellon, Syracuse University and University of Michigan. His expertise and interests span bio-molecular structure-dynamics, origins of primitive cells and type-2 diabetes

Abstract:

It is argued - why the preferred method to maintain euglycemia in type-2 should be prioritizing the endogenous insulin secretion, while suggesting possible approaches to research further in that direction. It is known, that most types of peripherally administered insulin (PAI) have drawbacks; viz. being non-native, lacking c-peptide, not mimicking physiological insulin secretion oscillations (ISO) that reduce insulin receptor saturation, contributing to weight gain (often as visceral fat). Also, PAI is far less effective in countering gluconeogenesis, a contributor to hyperglycemia, as it doesn’t mimic pancreatic release of insulin into the hepatic entrance of the portal vein as triggered by feeding. Merely maintaining tight-glycemic control may not necessarily reduce endothelial dysfunction. Hence, it may be more beneficial to steer away from PAI as well as exogenous insulin. Although, recent research demonstrates the merits of portally administered insulin, access to the portal vein is not practical. Clearly, stem cells are the right approach and deserve high priority. While DPP4-I/GLP-1, even with concomitant Glitazones, is good therapeutic approaches, they remain insufficient to achieve tight glycemic control. They, also, fail to mimic the ISO and feeding correlated hepatic portal secretion. Meanwhile it may be beneficial to revisit insulin secretagogues (IS) and modify traditional therapy, while improving approaches to endogenous secretion and concomitantly minimizing side effects. Dosage of sulfonylureas should be reduced to maintain a very basal secretion. This should be co-administered with a short acting IS (e.g. meglitinides) prior to feeding. This approach can be titrated to mimic native secretion. Effort should be made to find new molecules that enhance secretion efficiency while minimizing side effects. While β-cell ion channels have been exploited, more effort is needed to exploit the glycolysis/glucokinase aspect

Biography:

Walid Al-Qerem has received his PhD in Clinical Pharmacy Sunderland University in 2013. He has been working as an Assistant Professor at the Faculty of Pharmacy of Al-Zaytoonah University of Jordan since 2014. His research interests include Quality of Life especially for diabetics and respiratory medicine, which involves the standardization of spirometry.

Abstract:

Diabetes quality of life (DQOL) instrument has been broadly used to evaluate quality of life among diabetics. This study aims to develop a revised validated Arabic version of DQOL questionnaire in diabetic patients in Jordan. Patients were enrolled in this cross-sectional study from 1^st, January through April/2019 at several public health clinics in Jordan. The original DQOL questionnaire was translated to Arabic and then back-translated by a different translator, then the two versions were compared. Prior to circulating the final version of the questionnaire cognitive validity test were applied to ensure that all the questions were clear. Then a questionnaire that included demographical and other health related questions in addition to the final Arabic version of the DQOL was circulated to the participants. The data of the questionnaire were analyzed using exploratory factor analysis and confirmatory factor analysis after excluding duplicated questions and questions that included more than 15% missing data, also Cronbach alpha was conducted to confirm internal consistency. This study developed a validated Arabic version of DQOL that can measure quality of life of diabetics in the Arabic speaking world.

Biography:

Sergio Wehinger Wehinger has completed his PhD in Biomedical Sciences from University of Chile in 2013 and actually is an Associate Professor and Director of Magister in Biomedical Sciences of University of Talca in Chile. He had published papers in the field of Metabolism and Diabetes and he is currently investigating the molecular mechanisms involved in the cellular failure of the beta pancreatic islets, which is induced by elevated free fatty acids and oxidative stress levels, to elucidate how to prevent these processes

Abstract:

Background: Deleterious effects of high levels of free fatty acids lead to a phenomenon known as “lipotoxicity”, associated with insulin resistance and beta pancreatic cell damage, key events in development of type 2 diabetes mellitus. Lipotoxicity has been associated with cellular oxidative stress and beta-cell apoptosis. Caveolin-1 is a membrane protein that has been associated with many cellular functions as cell signalling regulation and apoptosis, and it is normally present in beta pancreatic cells. We previously reported that the expression of the membrane protein Caveolin-1 promotes free fatty acids-induced apoptosis in vitro in a mouse beta cell line; remains to be elucidated if this phenomenon is relevant in vivo.

Methods: We used C57BL6J mice lacking expression of Caveolin-1 (CAV-1 K.O. mice). We evaluated free fatty acids and triglycerides levels in blood in fasting conditions, oral glucose tolerance test (OTTG), carbonylated proteins in serum and C-peptide in wild type (WT) and Caveolin-1 K.O. and wild type mice exposed to a high fat diet for three months. Also, the presence of apoptosis was evaluated by TUNEL staining in beta pancreatic islets.

Results: The results indicated that we found that CAV-1 K.O. mice fed with high fat diet showed higher levels of triglycerides, cholesterol, free fatty acids and carbonylated proteins, although also a better response OGTT and C-peptide levels. Islets from K.O. mice showed lower levels of apoptosis.

Conclusion: Although K.O. mice showed a lipotoxic profile, our results suggest that their pancreatic islets were more resistant to the high fat diet deleterious effects over beta cells

Biography:

Kseniia Sokolova entered PhD student’s courses at Ural Federal University in 2016. She is a Junior Researcher at the Chair of Medicine Biochemistry and Biophysics of Ural State University and at the Laboratory of Biochemistry and Biophysics of Institute of Immunology and Physiology Ural Branch Russian Academy of Science. She is interested in Diabetes and Regeneration. Since 2016 she has published 14 papers and conference abstracts.

Abstract:

Introduction: Diabetes mellitus type 2 (DM2) is always accompanied by inflammation and destruction of β-cells. Cytokines, secreted by macrophages, are the main mediators of inflammatory and regenerative processes. In previous studies we demonstrated partial recovery of functional activity of β-cells at the injections of sodium phthalhydrazide, which changes macrophage phenotype M1→M2 and reduce inflammation.

Objective: The main objective of this study is the peculiarities of islet β-cells regeneration at DM2 and at modulation activity of macrophages.

Materials & Methods: Twenty (20) Wistar adult rats were divided into four groups: one –control; two and three – 30 and 60 days of streptozotocin/nicotinamide-induced diabetes correspondingly; four – 30 days of diabetes + injections of sodium phthalhydrazide. White blood parameters were evaluated on a hemoanalyzer. Cytokines were measured in blood and pancreas using ELISA method. Insulin+, KI67+cells were detected by immunohistochemistry. Detection of DNA fragmentation in apoptotic cells was made by TUNEL method kits.

Results: The results indicated that at the experimental diabetes quantity of white blood cells (WBC), lymphocytes and pro-inflammatory cytokines TNFα and Ifnγ in blood significantly increases. Concentration of anti-inflammatory TGFβ decreases both in blood and in pancreas. Sodium phthalhydrazide reduces quantity of WBC and lymphocytes and concentration of Ifnγ in blood and level of TNFα in pancreas. At 30th day of diabetes quantity of apoptotic β-cells increases and Ki67+β-cells are appeared. At sodium phthalhydrazide, quantity of Ki67+ β-cells increases significantly, while the quantity of apoptotic cells decreases. General and local inflammation at diabetes leads to the destructive-degenerative processes in pancreas, while modulation activity of macrophages, which reduces inflammation, intensifies islet regeneration.

Biography:

Angelo Michele Carella (MD) has completed his graduation in Medicine, after graduating he has obtained specialization in Internal Medicine, university Master in Healthcare Management and postgraduate courses on Diabetes and Obesity. He is a Medical Doctor at the Internal Medicine in the Department of "T. Masselli - Mascia" Hospital in San Severo (Italy). He was a past teacher in Health Professions degree course of Foggia University.And served as an Editorial Board Member/Reviewer of several scientific journals, author of about 50 scientific publications (Google Scholar h-index 5). He is a Member of D&CVD EASD Study Group, Investigator in clinical studies (DAVID, ESPORT, ATA-AF, DIAMOND) published in international journals, and Speaker at numerous scientific congresses and meetings. Rregistered in Google Scholar and Research Gate.

Abstract:

microRNAs (miRNAs), short noncoding RNA sequences, regulate several biological processes as cell differentiation, proliferation and development, cell-to-cell communication, cell metabolism and apoptosis. miRNAs seem also regulate insulin signaling, immune-mediated inflammation, adipokine expression, adipogenesis, lipid metabolism, and food intake. miRNAs may have a role in molecular mechanisms linked to cellular pathways of some diseases, as viral infections, cancer, diabetes, obesity and cardiovascular disease. Dysregulation of several miRNAs involves different aspects of diabetic disease: glycemic control, residual beta cell function, insulin secretion and sensitivity, micro- and macro-vascular complications as endothelial dysfunction, renal disease and retinopathy. The recent discovery of circulating miRNAs (c-miRNAs) easily detectable and measurable in plasma and other body fluids, led to the hypothesis of their potential role as disease indicators. Altered levels of several c-miRNAs were found to be linked to type 1 and type 2 diabetes, both at onset and in advanced disease. A lot of c-miRNAs are consistently dysregulated in diabetic patients and miR-126 was confirmed to be the most linked to pathways and development of type 1 and type 2 diabetes and their complications. Altered expression of other c-miRNAs correlates to obesity and its complications. Different levels of some c-miRNAs were found significantly associated with weight gain, but most of the data concern comorbidities and complications of obesity as insulin resistance, pre-diabetes, diabetes, dyslipidemia, adipogenesis dysregulation and inflammatory processes. Moreover, several evidences were obtained in obese children, in newborns and in maternal pre-gestational and gestational obesity. In particular the expression of some c-miRNAs differs in infants born to obese women compared with those born to lean women and these biomarkers might be useful in predicting future risk of obesity in children. At last, down-regulation of different c-miRNAs was observed in overweight/obese subjects after low or high glycemic index diet and after low-fat diet; c-miRNAs might also be potential novel biomarkers for the benefits of bariatric surgery and the effects of mild exercise. In conclusion, there are scientific evidences suggesting a potential role of c-miRNAs detection as diagnostic, prognostic and therapeutic biomarkers in obese and diabetic patients. Major limits: number, duration and sample size of clinical studies are small; source of c-miRNAs, extraction procedures, quantities of blood samples and methods of analysis were promiscuous and not well standardized; high costs required for c-miRNAs detection. The uncertainty observed in literature highlights the need for reproducible and well standardized methods as well as low-cost and wide availability assays to detect c-miRNAs with high sensitivity/specificity. Large, long-term and randomized controlled clinical studies are need to determine whether c-miRNAs can play a role as biomarkers for obesity and diabetes in daily clinical practice.

Biography:

Angelo Michele Carella (MD) has completed his graduation in Medicine, after graduating he has obtained specialization in Internal Medicine, university Master in Healthcare Management and postgraduate courses on Diabetes and Obesity. He is a Medical Doctor at the Internal Medicine in the Department of "T. Masselli - Mascia" Hospital in San Severo (Italy). He was a past teacher in Health Professions degree course of Foggia University.And served as an Editorial Board Member/Reviewer of several scientific journals, author of about 50 scientific publications (Google Scholar h-index 5). He is a Member of D&CVD EASD Study Group, Investigator in clinical studies (DAVID, ESPORT, ATA-AF, DIAMOND) published in international journals, and Speaker at numerous scientific congresses and meetings. Rregistered in Google Scholar and Research Gate.

Abstract:

microRNAs (miRNAs), short noncoding RNA sequences, regulate several biological processes as cell differentiation, proliferation and development, cell-to-cell communication, cell metabolism and apoptosis. miRNAs seem also regulate insulin signaling, immune-mediated inflammation, adipokine expression, adipogenesis, lipid metabolism, and food intake. miRNAs may have a role in molecular mechanisms linked to cellular pathways of some diseases, as viral infections, cancer, diabetes, obesity and cardiovascular disease. Dysregulation of several miRNAs involves different aspects of diabetic disease: glycemic control, residual beta cell function, insulin secretion and sensitivity, micro- and macro-vascular complications as endothelial dysfunction, renal disease and retinopathy. The recent discovery of circulating miRNAs (c-miRNAs) easily detectable and measurable in plasma and other body fluids, led to the hypothesis of their potential role as disease indicators. Altered levels of several c-miRNAs were found to be linked to type 1 and type 2 diabetes, both at onset and in advanced disease. A lot of c-miRNAs are consistently dysregulated in diabetic patients and miR-126 was confirmed to be the most linked to pathways and development of type 1 and type 2 diabetes and their complications. Altered expression of other c-miRNAs correlates to obesity and its complications. Different levels of some c-miRNAs were found significantly associated with weight gain, but most of the data concern comorbidities and complications of obesity as insulin resistance, pre-diabetes, diabetes, dyslipidemia, adipogenesis dysregulation and inflammatory processes. Moreover, several evidences were obtained in obese children, in newborns and in maternal pre-gestational and gestational obesity. In particular the expression of some c-miRNAs differs in infants born to obese women compared with those born to lean women and these biomarkers might be useful in predicting future risk of obesity in children. At last, down-regulation of different c-miRNAs was observed in overweight/obese subjects after low or high glycemic index diet and after low-fat diet; c-miRNAs might also be potential novel biomarkers for the benefits of bariatric surgery and the effects of mild exercise. In conclusion, there are scientific evidences suggesting a potential role of c-miRNAs detection as diagnostic, prognostic and therapeutic biomarkers in obese and diabetic patients. Major limits: number, duration and sample size of clinical studies are small; source of c-miRNAs, extraction procedures, quantities of blood samples and methods of analysis were promiscuous and not well standardized; high costs required for c-miRNAs detection. The uncertainty observed in literature highlights the need for reproducible and well standardized methods as well as low-cost and wide availability assays to detect c-miRNAs with high sensitivity/specificity. Large, long-term and randomized controlled clinical studies are need to determine whether c-miRNAs can play a role as biomarkers for obesity and diabetes in daily clinical practice.

Biography:

Mukhlynina has completed her PhD from Ural Federal University. She is the Researcher of Institute of Immunology and Physiology, Laboratory of Morphology and Biochemistry. She has published more than seven papers in reputed journals. The field of her scientific interest belongs to connective tissue physiology and regeneration.

Abstract:

We have studied 2-aminopropylmorpholino-5-phenyl-6H-1, 3, 4-thiadisine dihydrobromide (L-14) and 2-morpholino-5-phenyl-6H-1, 3, 4-thiadiazine hydrobromide (L-17), which combine antioxidant and antiglycative properties. The absence of myelotoxic effect is required for antidiabetic agents. So the aim of this research is to reveal hematological changes in diabetes rats treated with L-14 and L-17. Forty (40) male Wistar rats were used in accordance with the ethical principles of the Directive 2010/63/EU, divided into four groups: control, alloxan diabetes (AD), alloxan diabetes plus L-14, alloxan diabetes plus L-17. Rats were given alloxan injections (100 mg/kg/day, i.p., three days) to induce type-1 diabetes. L-14 and L-17 was injected intramuscularly (40 mg/kg/day, simultaneously with alloxan, 12 injections for four weeks). Hematological analysis of peripheral blood was performed by hemoanalyser Celly70 (Biocode Hycel). Alloxan diabetes after 30 days leads to significantly increase of mean corpuscular hemoglobin concentration (MCHC), erythrocyte anisocytosis (RDW), neutrophilic leukopenia, low platelet count and mean platelet volume (MPV). L-14 reduces MCH, MCHC and WBC, but not the RDW-changes. L-14 also causes significant increase in platelet count in comparison to control rats and MPV-recovery. L-17-treatment leads to increase in hemoglobin, MCH, MPV and platelet distribution width. But MCHC and RDW return to the physiological norm. Neutrophilic leukopenia persists at the level of AD-group. We have not found any myelotoxic effects of L-14 and L-17. Some hematological changes of AD-rats were recovered by investigated compounds, so, L-14 and L-17 are promising for the metabolic correction in diabetic conditions. The study was supported by the Russian Science Foundation grant 16-15-0039-П

Biography:

Will Jervis has graduated in Medicine and Surgery from Newcastle University in 2017. He has recently completed his Foundation Training in East Yorkshire at Hull Royal Infirmary in 2019. During his foundation training he has worked in Diabetes and Endocrinology and developed a keen interest in Thyroid Disorders and Osteoporosis. Over the past year he has created and organized a regional teaching programme for medical students in association with Hull York Medical School and has a publication in BMJ case reports.

Abstract:

Denosumab is a monoclonal antibody that is approved in the United States and Europe for the treatment of osteoporosis. Denosumab is typically given every six months and there is no current requirement for monitoring or dose adjustment in renal impairment. We present a case of a patient with chronic kidney disease stage four who presented with a generalized tonic clonic seizure and prolonged QT secondary to severe hypocalcaemia (1.43 mmol/L) 13 days after receiving a single dose of denosumab as treatment for osteoporosis. The patient was therefore commenced on an intravenous calcium infusion, which restored her calcium to near normal range and she had no further seizure activity. This report highlights the severe hypocalcaemia that can develop from a single dose of denosumab. We recommend that further monitoring of eGFR/serum calcium/vitamin D is required prior and post dosing of denosumab to help immediately recognize and treat life-threatening hypocalcaemia following denosumab administration.

Biography:

Kamila Szymanska is a third year PhD student in the Department of Biochemistry and Molecular Biology at Medical University of Lublin. Her project under the supervision of Prof. Adolfo Rivero-Müller is aimed to create a molecular characterization of gonadotropins and gonadotropin receptors. She has published 12 papers, in which she is either an author or co-author, she took part in more than 15 conferences and received many scholarships for her scientific achievements. Furthermore, she is a Principal Investigator of pre-doctoral grant PRELUDIUM funded by National Science Centre in Poland

Abstract:

Three novel compound heterozygous mutations in LHCGR gene were identified in male patient with disorder of sex development (DSD). Two of these mutations, p.L16Q missense mutation and a deletion p.K12_L15del were of paternal origin, whereas the third of the mutations was a duplication p.L10_Q17dup of maternal origin. In order to understand the effect of these mutations on the phenotype observed in the patient, a number of molecular studies were carried out. First, we separated the missense mutation from p.K12_L15del and p.L10_Q17dup mutations, so we could study them separately. Analyses include the measurement of the membrane expression of the receptors, gene and protein expression, measurement of cAMP production and investigation of its cellular localization and transport. The results of the study revealed that the surface expression of mutants was decreased as compared to the WT LHCGR. Confocal microscopy showed intracellular expression of p.L10_Q17dup and p.L16Q mutations, whereas the intracellular expression of p.K12_L15del was negligible. The cAMP production was significantly lower in the case of p.L10_Q17dup mutant as compared to the WT LHCGR stimulation. The cAMP production of p.L16Q was 2.4 times lower, whereas p.K12_L15del did not show any response upon stimulation. Furthermore, both mRNA and protein expression of all three mutant receptors was decreased. We present here three novel mutations that lead to complete inactivation of LHCGR. Duplication mutant is most likely being degraded within the endoplasmic reticulum, p.K12_L15del results in mRNA degradation, whereas the expression of p.L16Q receptor is associated with decreased membrane expression of the receptor