E L Los

Publication Details
Article Title: Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus.

First Author: E L Los

All Authors: Los EL, Deen PM, Robben JH

Journal Title: Journal of neuroendocrinology

Abstract: According to the body's need, water is reabsorbed from the pro-urine that is formed by ultrafiltration in the kidney. This process is regulated by the antidiuretic hormone arginine-vasopressin (AVP), which binds to its type 2 receptor (V2R) in the kidney. Mutations in the gene encoding the V2R often lead to the X-linked inheritable form of nephrogenic diabetes insipidus (NDI), a disorder in which patients are unable to concentrate their urine despite the presence of AVP. Many of these mutations are missense mutations that do not interfere with the intrinsic functionality of V2R, but cause its retention in the endoplasmic reticulum (ER), making it unavailable for AVP binding. Because the current treatments for NDI relieve its symptoms to some extent, but do not cure the disorder, cell-permeable antagonists (pharmacological chaperones) have been successfully used to stabilise the mutant receptors and restore their plasma membrane localisation. Recently, cell-permeable agonists also were shown to rescue ER-retained V2R mutants, leading to increased cAMP levels and translocation of aquaporin-2 to the apical membrane. This makes V2R-specific cell-permeable agonists very promising therapeutics for NDI as a result of misfolded V2R receptors.

Related Articles

Short Communication Open Access Canada Journal of Psychiatry and Psychiatric Disorders Volume 1, Issue 5

The Diathesis-Stress Model: Psychosocial Stressors, Trauma and Diabetes

Research Article Open Access Ghana Archives of Clinical and Biomedical Research Volume 1, Issue 4
Prevalence and Risk Factors of Diabetes Mellitus Among the Inhabitants of Kumasi Metropolis
Research Article Open Access Ghana Archives of Clinical and Biomedical Research Volume 1, Issue 5
Prevalence of the Complications of Diabetes in Developing Countries
Review Article Open Access India Archives of Clinical and Biomedical Research Volume 1, Issue 1
Biochemistry and Pathophysiology of Glycation of DNA: Implications in Diabetes
Case Report Open Access Turkey Archives of Clinical and Medical Case Reports Volume 1, Issue 3

Severe Rhino-orbital Mucormycosis Infection of anIntensive Care Unit Patient: A Case Report

Research Article Open Access Iraq Archives of Internal Medicine Research Volume 1, Issue 1

Knowledge and Attitude About Sweeteners Among Type 2 Diabetic Patients

Research Article Open Access Ireland Archives of Clinical and Medical Case Reports Volume 2, Issue 6

Motivational Interviewing for Poorly Controlled Type 2 Diabetics in a Rural South African Community

Research Article Open Access Saudi Arabia Archives of Clinical and Medical Case Reports Volume 2, Issue 5

Evaluate the Effect of Education Interventions in the Prevention of Diabetic Foot Ulcers through Knowledge of the Disease and Self-Care Practices in Saudi Arabia

Mini Review Article Open Access Colombia Cardiology and Cardiovascular Medicine Volume 1, Issue 4

Diabetic Cardiomyopathy: Cause or Consequence of Diabetes Mellitus?

Reproductive health
Validation of a symphysis-fundal height chart developed for pregnancy complicated by diabetes and hyperglycemia: an observational study.

Authors: de Sousa Basso NA, Morceli G, Costa R, Dias A, Rudge MVC, Calderon IMP

Abstract: The present study validates a symphysis-fundal height chart (SFH-chart) for pregnant women with type 2 diabetes mellitus (DM2), gestational diabetes mellitus (GDM) and mild gestational hyperglycemia (MGH) attending at the Diabetes and Pregnancy Reference Service of the Botucatu Medical School, UNESP, Brazil.A cross-sectional study was carried out to evaluate the performance of the specific FHC in predicting small (SGA) and large (LGA) for gestational age newborns (NB). We evaluated 206 pregnant women with DM2, GDM or MGH and their NB. The last symphysis-fundal height measure, taken at birth, was used to determine the sensitivity index (Sens), specificity index (Spe), positive prediction value (PPV), negative prediction value (NPV) and accuracy in predicting SGA and LGA. The gold standard was the Lubchenco birth weight/gestational age ratio evaluated at birth.The mothers showed adequate glycemic control; 91.3 % of all pregnant women achieved HbA1c?

Social science & medicine (1982)
What do physicians gain (and lose) with experience? Qualitative results from a cross-national study of diabetes.

Authors: Elstad EA, Lutfey KE, Marceau LD, Campbell SM, von dem Knesebeck O, McKinlay JB

Abstract: An empirical puzzle has emerged over the last several decades of research on variation in clinical decision making involving mixed effects of physician experience. There is some evidence that physicians with greater experience may provide poorer quality care than their less experienced counterparts, as captured by various quality assurance measures. Physician experience is traditionally narrowly defined as years in practice or age, and there is a need for investigation into precisely what happens to physicians as they gain experience, including the reasoning and clinical skills acquired over time and the ways in which physicians consciously implement those skills into their work. In this study, we are concerned with 1) how physicians conceptualize and describe the meaning of their clinical experience, and 2) how they use their experience in clinical practice. To address these questions, we analyzed qualitative data drawn from in-depth interviews with physicians from the United States, United Kingdom, and Germany as a part of a larger factorial experiment of medical decision making for diabetes. Our results show that common measures of physician experience do not fully capture the skills physicians acquire over time or how they implement those skills in their clinical work. We found that what physicians actually gain over time is complex social, behavioral and intuitive wisdom as well as the ability to compare the present day patient against similar past patients. These active cognitive reasoning processes are essential components of a forward-looking research agenda in the area of physician experience and decision making. Guideline-based outcome measures, accompanied by underdeveloped age- and years-based definitions of experience, may prematurely conclude that more experienced physicians are providing deficient care while overlooking the ways in which they are providing more and better care than their less experienced counterparts.

BMC medical genetics
A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population.

Authors: Sugunan D, Nair AK, Kumar H, Gopalakrishnapillai A

Abstract: Glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which plays a crucial role in the secretion of insulin upon food stimulus and in the regulation of postprandial glucose level. It also exerts an effect on the synthesis and secretion of lipoprotein lipase, from adipocytes, important for lipid metabolism. The aim of our study was to do a case-control association analysis of common variants in GIP in association with type 2 diabetes and related biochemical parameters.A total of 2000 subjects which includes 1000 (584M/416F) cases with type 2 diabetes and 1000 (470M/530F) normoglycemic control subjects belonging to Dravidian ethnicity from South India were recruited to assess the effect of single nucleotide polymorphisms (SNPs) in GIP (rs2291725, rs2291726, rs937301) on type 2 diabetes in a case-control manner. The SNPs were genotyped by using tetra primer amplification refractory mutation system-PCR (ARMS PCR). For statistical analysis, our study population was divided into sub-groups based on gender (male and female). Association analysis was carried out using chi-squared test and the comparison of biochemical parameters among the three genotypes were performed using analysis of covariance (ANCOVA).Initial analysis revealed that, out of the total three SNPs selected for the present study, two SNPs namely rs2291726 and rs937301 were in complete linkage disequilibrium (LD) with each other. Therefore, only two SNPs, rs2291725 and rs2291726, were genotyped for the association studies. No significant difference in the allele frequency and genotype distribution of any of the SNPs in GIP were observed between cases and controls (P > 0.05). Analysis of biochemical parameters among the three genotypes showed a significant association of total cholesterol (P = 0.042) and low density lipoprotein (LDL) with the G allele of the SNP rs2291726 in GIP (P = 0.004), but this was observed only in the case of female subjects. However this association does not remain significant after correction for multiple testing by Bonferroni's inequality method.No statistically significant association was observed between any of the SNPs analysed and type 2 diabetes in our population. But the analysis of biochemical parameters indicates that the G allele in rs2291726 may be a putative risk allele for increased LDL cholesterol and further studies in other population needs to be carried out for ascertaining its role in cholesterol metabolism and subsequent cardiovascular risk.

Vnitrni lekarstvi
[Treatment of diabetic macular oedema in a type 1 diabetes patient--mistakes in interdisciplinary collaboration].

Authors: Veith M

Abstract: Diabetic retinopathy (DR) is a significant microvascular complication of diabetes. High quality interdisciplinary collaboration is an important aspect ofa successful DR therapy. A case ofa 41-year-old diabetic is presented below, who has been in our care for almost four years. His Diabetes ID card only contains his current glycaemia values. Although the patient had been regularly given a report for his diabetologist with a request for additional information, we have only obtained one value of glycated haemoglobin through the course of the patient's dispensarisation. For this reason, and the non-stabilisation of DR, we have recommended that the patient starts to see a different diabetologist.

Diabetes & vascular disease research
Sensor and software use for the glycaemic management of insulin-treated type 1 and type 2 diabetes patients.

Authors: Ajjan RA, Abougila K, Bellary S, Collier A, Franke B, Jude EB, Rayman G, Robinson A, Singh BM

Abstract: Lowering glucose levels, while avoiding hypoglycaemia, can be challenging in insulin-treated patients with diabetes. We evaluated the role of ambulatory glucose profile in optimising glycaemic control in this population. Insulin-treated patients with type 1 and type 2 diabetes were recruited into a prospective, multicentre, 100-day study and randomised to control (n?=?28) or intervention (n?=?59) groups. The intervention group used ambulatory glucose profile, generated by continuous glucose monitoring, to assess daily glucose levels, whereas the controls relied on capillary glucose testing. Patients were reviewed at days 30 and 45 by the health care professional to adjust insulin therapy. Comparing first and last 2?weeks of the study, ambulatory glucose profile-monitored type 2 diabetes patients (n?=?28) showed increased time in euglycaemia (mean?±?standard deviation) by 1.4?±?3.5?h/day (p?=?0.0427) associated with reduction in HbA1c from 77?±?15 to 67?±?13?mmol/mol (p?=?0.0002) without increased hypoglycaemia. Type 1 diabetes patients (n?=?25) showed reduction in hypoglycaemia from 1.4?±?1.7 to 0.8?±?0.8?h/day (p?=?0.0472) associated with a marginal HbA1c decrease from 75?±?10 to 72?±?8?mmol/mol (p?=?0.0508). Largely similar findings were observed comparing intervention and control groups at end of study. In conclusion, ambulatory glucose profile helps glycaemic management in insulin-treated diabetes patients by increasing time spent in euglycaemia and decreasing HbA1c in type 2 diabetes patients, while reducing hypoglycaemia in type 1 diabetes patients.

BMC public health
Individual-based primary prevention of cardiovascular disease in Cambodia and Mongolia: early identification and management of hypertension and diabetes mellitus.

Authors: Otgontuya D, Oum S, Palam E, Rani M, Buckley BS

Abstract: To assess the coverage of individual-based primary prevention strategies for cardiovascular disease (CVD) in Cambodia and Mongolia: specifically the early identification of hypertension and diabetes mellitus, major proximate physiological CVD risk factors, and management with pharmaceutical and lifestyle advice interventions.Analysis of data collected in national cross-sectional STEPS surveys in 2009 (Mongolia) and 2010 (Cambodia) involving participants aged 25-64 years: 5433 in Cambodia and 4539 in Mongolia.Mongolia has higher prevalence of CVD risk factors than Cambodia--hypertension (36.5% versus 12.3%), diabetes (6.3% versus 3.1%), hypercholesterolemia (8.5% versus 3.2%), and overweight (52.5% versus 15.5%). The difference in tobacco smoking was less notable (32.1% versus 29.4%).Coverage with prior testing for blood glucose in the priority age group 35-64 years remains limited (16.5% in Cambodia and 21.7% in Mongolia). Coverage is higher for hypertension. A large burden of both hypertension and diabetes remains unidentified at current strategies for early identification: only 45.4% (Cambodia) to 65.8% (Mongolia) of all hypertensives and 22.8% (Mongolia) to 50.3% (Cambodia) of all diabetics in the age group 35-64 years had been previously diagnosed. Approximately half of all hypertensives and of all diabetics in both countries were untreated. 7.2% and 12.2% of total hypertensive population and 5.9% and 16.1% of total diabetic population in Cambodia and Mongolia, respectively, were untreated despite being previously diagnosed.Only 24.1% and 28.6% of all hypertensives and 15.9% and 23.9% of all diabetics in Mongolia and Cambodia, respectively were adequately controlled. Estimates suggest deficits in delivery of important advice for lifestyle interventions.Multifaceted strategies are required to improve early identification, initiation of treatment and improving quality of treatment for common CVD risk factors. Periodic population-based surveys including questions on medical and treatment history and the context of testing and treatment can facilitate monitoring of individual-based prevention strategies.

Noninvasive assessment of subclinical atherosclerosis in normotensive gravidae with gestational diabetes.

Authors: Atay AE, Simsek H, Demir B, Sakar MN, Kaya M, Pasa S, Demir S, Sit D

Abstract: Carotid artery intima-media thickness (CIMT), hyperhomocysteinemia, microalbuminuria, and nitric oxide reflect subclinical atherosclerosis and predict the risk of future cardiovascular events. We aimed to evaluate the presence of subclinical atherosclerosis and endothelial dysfunction in normotensive patients with gestational diabetes mellitus (GDM) noninvasively.We enrolled 41 normotensive patients with GDM and 44 healthy gravidae in the study. Serum homocysteine and nitric oxide levels, urinary albumin excretion (microalbuminuria), and CIMT were evaluated along with lipid parameters and anthropometric measurements.Patients with GDM had significantly higher levels of serum homocysteine, urinary albumin excretion, and increased CIMT (p?

Liver international : official journal of the International Association for the Study of the Liver
Diabetes pattern on the 75 g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus.

Authors: Konishi I, Hiasa Y, Shigematsu S, Hirooka M, Furukawa S, Abe M, Matsuura B, Michitaka K, Horiike N, Onji M

Abstract: Patients with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes mellitus (DM) has been proposed to be a risk factor for hepatocellular carcinoma (HCC).The aim of this study is to clarify the influence of glucose intolerance as evaluated by the 75 g oral glucose tolerance test (OGTT) on hepatocarcinogenesis in patients with HCV.This study was carried out in a cohort of 197 patients with HCV who had not been previously diagnosed as having DM. All patients underwent the 75 g OGTT at entry. They were also screened for HCC and, thereafter, the rate of hepatocarcinogenesis was compared between the patients with and without glucose intolerance.Based on the results of the 75 g OGTT, 125 (63%) had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance (IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients with the DM pattern than in patients with either NGT or IGT. Even in patients without advanced liver fibrosis, HCC was more frequently observed in patients with DM than in patients with NGT. A multiple logistic regression analysis showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age and gamma-glutamyltransferase to all be independent risk factors related to hepatocarcinogenesis.A DM pattern on the 75 g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g OGTT is considered to be useful for identifying this risk factor for HCC in patients with HCV.

Can technological solutions for diabetes replace islet cell function?

Authors: Gregory JM, Moore DJ

Abstract: The central objective of diabetes research and management is to restore the deficient secretion of insulin, thereby restoring a state of euglycemia and minimizing short- and long-term risks associated with poor glucose control. The development of the artificial pancreas seeks to imitate the action of the pancreatic beta cell by employing closed-loop control to respond to glycemic excursions by appropriately infusing appropriate amounts of insulin. This article examines progress towards implementing an artificial pancreas in the context of the pancreatic islet as the ideal model for controlling blood glucose. Physiologic insulin secretion will form our foundation for considering the technical design elements relevant to electromechanically imitating the beta cell. The most recent clinical trials using closed-loop control are reviewed and this modality is compared to other curative approaches including islet cell transplantation and preservation. Finally, the potential of the artificial pancreas as a method to adequately reestablish euglycemia is considered.

Thrombosis and haemostasis
Inflammation and thrombosis in diabetes.

Authors: Hess K, Grant PJ

Abstract: Patients with diabetes mellitus are at increased risk of cardiovascular morbidity and mortality. Atherothrombosis, defined as atherosclerotic lesion disruption with superimposed thrombus formation, is the most common cause of death among these patients. Following plaque rupture, adherence of platelets is followed by local activation of coagulation, the formation of a cross-linked fibrin clot and the development of an occlusive platelet rich fibrin mesh. Patients with diabetes exhibit a thrombotic risk clustering which is composed of hyper-reactive platelets, up regulation of pro-thrombotic markers and suppression of fibrinolysis. These changes are mainly mediated by the presence of insulin resistance and dysglycaemia and an increased inflammatory state which directly affects platelet function, coagulation factors and clot structure. This prothrombotic state is related to increased cardiovascular risk and may account for the reduced response to antithrombotic therapeutic approaches, underpinning the need for adequate antithrombotic therapy in patients with diabetes to reduce their cardiovascular mortality.

News & Announcements

Submit your latest research work to our esteemed journals and publish your articles withour any charges in some of our journals

Follow Us