Journal of endocrinology and diabetes最新文献

{"title":"Circulating Neurotoxic 5-HT2A Receptor Agonist Autoantibodies in Adult Type 2 Diabetes with Parkinson's Disease.","authors":"Mark B Zimering","doi":"10.15226/2374-6890/5/2/01102","DOIUrl":"10.15226/2374-6890/5/2/01102","url":null,"abstract":"<p><strong>Aims: </strong>To test whether circulating neurotoxic autoantibodies increase in adult type 2 diabetes mellitus with Parkinson's disease (PD) or dementia. To identify the G-protein coupled receptor on neuroblastoma cells mediating neural inhibitory effects in diabetic Parkinson's disease plasma autoantibodies. To determine the mechanism of accelerated neuroblastoma cell death and acute neurite retraction induced by diabetic Parkinson's disease and dementia autoantibodies.</p><p><strong>Methods: </strong>Protein-A eluates from plasma of twelve older adult male diabetic patients having Parkinson's disease (n=10) or dementia (n=2), and eight age-matched control diabetic patients were tested for ability to cause accelerated N2A neuroblastoma cell death and acute neurite retraction. Specific antagonists of G protein coupled receptors belonging to the G alpha q subfamily of heterotrimetric G-proteins, the phospholipase C/inositol triphosphate/Ca2+ pathway, or the RhoA/Rho kinase pathway were tested for ability to block diabetic Parkinson's disease/dementia autoantibody-induced neurite retraction or N2A accelerated cell loss. Sequential Liposorber LA-15 dextran sulfate cellulose/protein-A affinity chromatography was used to obtain highly-purified fractions of diabetic Parkinson's disease autoantibodies.</p><p><strong>Results: </strong>Mean accelerated neuroblastoma cell loss induced by diabetic Parkinson's disease or dementia autoantibodies significantly exceeded (P = 0.001) the level of N2A cell loss induced by an identical concentration of the diabetic autoantibodies in control patients without these two co-morbid neurodegenerative disorders. Co-incubation of diabetic Parkinson's disease and dementia autoantibodies with two-hundred nanomolar concentrations of M100907, a highly selective 5-HT2AR antagonist, completely prevented autoantibody-induced accelerated N2A cell loss and neurite retraction. A higher concentration (500 nM-10μM) of alpha-1 adrenergic, angiotensin II type 1, or endothelin A receptor antagonists did not substantially inhibit autoantibody-induced neuroblastoma cell death or prevent neurite retraction. Antagonists of the inositol triphosphate receptor (2-APB, 50μM), the intracellular calcium chelator (BAPTA-AM, 30 μM) and Y27632 (10 μM), a selective RhoA/Rho kinase inhibitor, each completely blocked acute neurite retraction induced by sixty nanomolar concentrations of diabetic Parkinson's disease autoantibodies. Co-incubation with 2-APB (1-2 μM) for 8 hours' prevented autoantibody-induced N2A cell loss. The highly-purified fraction obtained after Liposorber LA/protein-A affinity chromatography in hypertriglyceridemic diabetic dementia and Parkinson's disease plasmas had apparent MWs > 30 kD, and displayed enhanced N2A toxicity requiring substantially higher concentrations of 5-HT2AR antagonists (M100907, ketanserin, spiperone) to effectively neutralize.</p><p><strong>Conclusion: </strong>These data suggest increased autoant","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990037/pdf/nihms969963.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Social Determinants of Type 2 Diabetes in a Coastal Area of Kerala, India.","authors":"S Aswathy,&nbsp;V Lohidas,&nbsp;Nimitha Paul,&nbsp;T S Anish,&nbsp;Tinu Narayanan,&nbsp;Brian Oldenburg","doi":"10.15226/2374-6890/4/3/00181","DOIUrl":"https://doi.org/10.15226/2374-6890/4/3/00181","url":null,"abstract":"<p><strong>Introduction: </strong>Varying prevalence rates of type 2 diabetes have been observed in different parts of the southern state of Kerala, India which is in an advanced stage of epidemiologic transition. Social patterning is evident in diabetes and therefore it was decided to undertake a study on estimating the prevalence of diabetes and associated social determinants.</p><p><strong>Methodology: </strong>The adopted local self administration unit of the Medical College which is also the field practice area with a population of 25,096 was taken for the study. All the households in the area were visited and the details regarding self reported diabetes was collected after obtaining informed consent and analysis done by multivariate logistic regression.</p><p><strong>Result: </strong>The prevalence of self reported diabetes in this coastal area was found to be low at 7.4%. Type 2 diabetes was also found to occur significantly earlier among the respondents belonging to the below poverty line. Age above 40 years (OR 2 95% CI 1.5-2.7, p=.000), marital status (OR 1.9 95% CI 1.1-2.1, p=.006) presence of comorbidities (OR 635 95% CI 389-969, p=.000), more than 8 years of schooling (OR 0.64 95% CI 0.46-0.86, p=.004), living conditions as represented by presence of household source of drinking water(OR 1.4 95% CI 1.01-1.5) were found to be independent predictors. Though there was increasing trend of diabetes among the forward caste line families after backward logistic regression this disappeared leaving behind the proxy of socioeconomic status, household source of drinking water.</p><p><strong>Conclusion: </strong>Though, the state of Kerala is in an advanced stage of epidemiologic transition, coastal areas are still in the earlier phases of transition with low prevalence of type 2 diabetes mellitus. Higher education and better living conditions are important social determinants of diabetes though further studies are necessary to delineate the impact of economic status and education.</p>","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815305/pdf/nihms916780.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35842947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes Autoantibodies Mediate Neural- and Endothelial Cell- Inhibitory Effects Via 5-Hydroxytryptamine- 2 Receptor Coupled to Phospholipase C/Inositol Triphosphate/Ca2+ Pathway.","authors":"Mark B Zimering","doi":"10.15226/2374-6890/4/4/00184","DOIUrl":"10.15226/2374-6890/4/4/00184","url":null,"abstract":"<p><strong>Aims: </strong>To identify the G-protein coupled receptor(s) on neuroblastoma and endothelial cells which mediate neural- and endothelial cell-inhibitory effects in plasma autoantibodies from a subset of older type 2 diabetes with neurologic and vascular co-morbidity. To determine the mechanism(s) of neurite retraction induced by diabetic pathologies' auto antibodies.</p><p><strong>Methods: </strong>Protein-A eluates from plasma of 11 diabetic patients having nephropathy, moderate-severe obesity and/or complications in which increased inflammation plays a role (depression, Parkinson's disease, atrial fibrillation, obstructive sleep apnea) were tested for neurite retraction and decreased survival in N2A neuroblastoma cells, and decreased survival in pulmonary artery endothelial cells. Specific antagonists of G protein coupled receptors belonging to the G alpha q subfamily of hetero trimetric G proteins or the phospholipase C/inositol triphosphate/Ca2+ pathway were tested for modulatory effects on diabetic pathologies' autoantibody-induced N2A neurite retraction, or cell survival.</p><p><strong>Results: </strong>Co-incubation with specific antagonists of the 5-hydroxytryptamine- 2A receptor significantly prevented acute N2A neurite retraction induced by 50-100 nM concentrations of diabetic pathologies' autoantibodies. Protection against neurite retraction (M100907> spiperone> ketanserin) closely paralleled the antagonists' potency order at the 5-HT2-AR. Neuroblastoma or endothelial cell death (after 24 hours incubation) with 50-100 nM autoantibodies was completely or nearly completely (91%) prevented by co-incubation with 200 nM M100907, a highly selective 5-HT2-AR antagonist. Alpha-1 adrenergic, angiotensin II, metabotropic glutamate 5, or endothelin A (100 nM-10µM) receptor antagonists did not substantially inhibit autoantibody-induced cell death. The intracellular calcium chelator (BAPTA-AM, 50 µM) and inhibitors of the inositol triphosphate (IP3) receptor (2-APB, 50µM), and phospholipase C-gamma (U73144, 1µM) each significantly protected against autoantibody-induced acute N2A neurite retraction.</p><p><strong>Conclusion: </strong>These data suggest that neural- and endothelial- inhibitory effects in autoantibodies from older adult diabetes with nephropathy and obesity/inflammation-associated complications are mediated by agonist autoantibodies directed against the 5-hydroxytryptamine 2 receptor positively coupled to the phospholipase C/inositol triphosphate/ cytosolic Ca2+ release pathway.</p>","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964990/pdf/nihms968539.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9597834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Neuronal Depolarization Evoked by Autoantibodies in Diabetic Obstructive Sleep Apnea: Role for Inflammatory Protease(s) in Generation of Neurotoxic Immunoglobulin Fragment.","authors":"Mark B Zimering, Zui Pan","doi":"10.15226/2374-6890/4/1/00168","DOIUrl":"10.15226/2374-6890/4/1/00168","url":null,"abstract":"<p><strong>11 aim: </strong>Obstructive sleep apnea increases in diabetes and morbid obesity. We tested a hypothesis that circulating autoantibodies in adult type 2 diabetes which increase in association with morbid obesity are capable of causing long-lasting neuronal depolarization and altered calcium release in mouse atrial cardiomyocytes.</p><p><strong>12 methods: </strong>Protein-A eluates from plasma of 14 diabetic obstructive sleep apnea patients and 17 age-matched diabetic patients without sleep apnea were tested for effects on depolarization and neurite out growth in N2a mouse neuroblastoma cells. The mechanism of autoantibody-mediated neurite outgrowth inhibition was investigated in co-incubation experiments of diabetic obstructive sleep apnea autoantibodies with specific antagonists of G-protein coupled receptors or the RhoA/Rho kinase signaling pathway. Following long-term storage of the protein-A eluates (to allow spontaneous proteolysis and IgG subunit dissociation), plasma autoantibodies from diabetic obstructive sleep apnea, cancer or control patients were compared for enhancement of inhibitory effects on endothelial cell survival. Size exclusion chromatography performed (in the presence or absence of a specific membrane type 1-matrix metalloproteinase inhibitor) was used to characterize the IgG autoantibody subunit(s) or fragments associated with peak neurotoxicity in diabetic obstructive sleep apnea.</p><p><strong>13 results: </strong>Diabetic obstructive sleep apnea (n = 14) autoantibodies caused a significant increase (P = 0.01) in membrane depolarization in N2a mouse neuroblastoma cells compared to control diabetic patients (n = 15) not suffering with obstructive sleep apnea. Process extension in N2A mouse neuroblastoma cells was significantly inhibited (P = 0.01) by diabetic obstructive sleep apnea (n = 9) autoantibodies compared to effects from identical 10 <i>μ</i>g/mL concentrations of control diabetic autoantibodies in patients without obstructive sleep apnea. Ten micromolar concentrations of SCH-202676, a G-protein coupled receptor antagonist (n = 5) or ten micromolar concentration of Y27632, a selective Rho kinase inhibitor (n = 6), each significantly prevented (P < 0.001) neurite outgrowth inhibition by diabetic obstructive sleep apnea autoantibodies. Autoantibodies in representative patients with obstructive sleep apnea and either atrial fibrillation or left ventricular hypertrophy evoked acute large increases in intracellular Ca²⁺ in HL-1 mouse atrial cardiomyocytes. The magnitude of intracellular Ca²⁺ release was dose-dependently significantly correlated to the electrocardiographic Cornell voltage-duration product. Gel filtration of diabetic obstructive sleep apnea autoantibodies revealed peak neurotoxicity associated with MWs corresponding to IgG light chain dimer(s), monomers or half-light chains as well as a novel <i>∼</i> 5.5 kD putative light chain fragment.</p><p><strong>14 conclusions: <","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966027/pdf/nihms967349.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9603702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxic Immunoglobulin Light Chain Autoantibodies are Associated with a Cluster of Severe Complications in Older Adult Type 2 Diabetes.","authors":"Mark B Zimering, N Mirkovic, M Pandya, J H Zimering, J A Behnke, S Thakker-Varia, J Alder, R J Donnelly","doi":"10.15226/2374-6890/3/1/00141","DOIUrl":"10.15226/2374-6890/3/1/00141","url":null,"abstract":"<p><strong>Aims: </strong>To assess neuronal depolarization evoked by autoantibodies in diabetic depression compared to depolarization evoked by autoantibodies in control patients. To determine whether a subset of severe (late-onset) diabetic complications may be mediated in part by toxic immunoglobulin light chains that may increase in diabetic nephropathy.</p><p><strong>Methods: </strong>Protein-A eluates from plasma of 21 diabetic depression patients and 37 age-matched controls were tested for depolarization in hippocampal or immature neurons. Subsets of depolarizing or non-depolarizing autoantibodies were tested for neurite outgrowth inhibition in N2A neuroblastoma cells or the ability to modulate Ca²⁺ release in HL-1 atrial cardiomyocytes or in endothelial cells. The stability of depolarizing autoantibodies was investigated by heat treatment (56°C × 30 minutes) or following prolonged exposure to the pro-protein convertase, furin. Gel filtration of active depolarizing autoantibodies was performed to determine the apparent molecular mass of peak neurotoxicity associated with the autoantibodies.</p><p><strong>Results: </strong>Diabetic depression (n = 21) autoantibodies caused significantly greater mean depolarization in neuroblastoma cells (<i>P < 0.01</i>) compared to autoantibodies in diabetic (n = 15) or non-diabetic (n = 11) patients without depression. Depolarizing autoantibodies caused significantly more (<i>P=0.011</i>) inhibition of neurite outgrowth in neuroblastoma cells than non-depolarizing autoantibodies (n = 10) and they evoked sustained, global intracellular Ca²⁺ release in atrial cardiomyocytes or in endothelial cells. A subset of older diabetic patients suffering with a cluster of nephropathy, non-ischemic cardiomyopathy and/or depression demonstrated the presence of stable light chain dimers having apparent MW of 46 kD and associated with peak neurotoxicity in neuroblastoma cells.</p><p><strong>Conclusion: </strong>These data suggest that autoantibodies in older adult diabetic depression cause long-lasting depolarization in hippocampal neurons including adult dentate gyrus neural progenitor cells. The autoantibodies may impair adult dentate gyrus neurogenesis associated with treatment-refractory depression via several mechanisms including suppression of neurite outgrowth, and alteration of membrane excitability. Stable, toxic light chain autoantibody components may contribute to a cluster of severe (late-onset) complications characterized by dysfunction in highly vascularized tissues.</p>","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963888/pdf/nihms967346.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9603700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Confronting Complacency in the Face of Calamity: Mobilizing for the Home Front War against Diabetes.","authors":"Dean Schillinger","doi":"10.15226/2374-6890/3/5/00163","DOIUrl":"https://doi.org/10.15226/2374-6890/3/5/00163","url":null,"abstract":"<p><p>Despite the damage Type 2 Diabetes (DM2) is wreaking on vulnerable families and communities, the US clinical, public health and scientific communities have not yet mobilized for a public health war against DM2. This war requires us to confront our \"diabetogenic\" society - characterized by sedentary lifestyles, marketing that push diets engorged with processed sugars, and neighborhoods where it is easier and safer to drive than walk. I describe 6 causes for this complacency, and highlight solutions from other recent socio-medical epidemics in which we overcame complacency to generate lifesaving policies. It is time for those fighting DM2 one small clinical battle at a time to become more active in shaping DM2 policy and enlist <i>en masse</i> in the larger policy war against DM2.</p>","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"3 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754011/pdf/nihms856489.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35714399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fitness Level is Associated with Sex-Specific Regional Fat Differences in Normal Weight Young Adults.","authors":"T. Bosch, D. Dengel, J. Ryder, A. Kelly, L. Chow","doi":"10.15226/2374-6890/2/3/00122","DOIUrl":"https://doi.org/10.15226/2374-6890/2/3/00122","url":null,"abstract":"OBJECTIVES\u0000To characterize regional body composition and insulin sensitivity differences between young adults who were normal weight with either high or low fitness determined by VO2 peak. We hypothesized that higher fitness levels would be associated with reduced visceral fat (VAT) and improved insulin sensitivity.\u0000\u0000\u0000DESIGN\u0000A cross-sectional comparison of normal weight males and females with high or low fitness matched on age and sex.\u0000\u0000\u0000METHODS\u0000A total of 38 (20M/18F) individuals were recruited for this study. Thirty-two young adults (18M/14F) were matched on age (mean 22.5 ± 3 yrs.) and BMI (22.4 ± 2.4 kg/m2) and sex and classified by high or low fitness based on VO2 peak difference (≥ 8ml/kg/min). Total and regional body composition, including VAT, was measured by Dual Energy X-Ray Absorptiometry (DXA). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. An analysis of variance compared regional body composition and insulin sensitivity between high and low fitness young adults with a normal BMI.\u0000\u0000\u0000RESULTS\u0000Higher fitness was associated with significantly lower percent body fat, lower android fat mass and higher insulin sensitivity in males (-7.2%, P<0.001; -0.5kg, P=0.048; 5.6mg/kg (FFM)/min, p=0.002). In females, higher fitness was associated with significantly lower percent body fat, lower leg fat but no difference in insulin sensitivity (-6.7%, P=0.001; -2.7kg, P<0.001; 2.5 mg/kg(FFM)/min, P=0.40). No differences in VAT were observed between high and low fitness groups. Interestingly in females, there was no difference in total lean mass, trunk lean mass or leg lean mass (P=0.59, P=0.17, P=0.99).\u0000\u0000\u0000CONCLUSION\u0000Higher fitness does not influence VAT in normal weight individuals. Sex influenced regional fat and insulin sensitivity differences between high fitness and low fitness groups.","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"198 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67332784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies in Human Diabetic Depression Inhibit Adult Neural Progenitor Cells <i>In vitro</i> and Induce Depressive-Like Behavior in Rodents.","authors":"Mark B Zimering, Joseph A Behnke, Smita Thakker-Varia, Janet Alder","doi":"10.15226/2374-6890/2/2/00119","DOIUrl":"10.15226/2374-6890/2/2/00119","url":null,"abstract":"<p><strong>Aim: </strong>Diabetic depression increases in association with microvascular complications. We tested a hypothesis that circulating autoantibodies having anti-endothelial and anti-neuronal properties increase in subsets of diabetes with co-morbid depression.</p><p><strong>Methods: </strong>Protein-A eluates from plasma of 20 diabetic depression patients and 30 age-matched controls were tested for effects on endothelial cell survival, neurite outgrowth in rat pheochromocytoma (PC12) cells, or process extension and survival in adult rat dentate gyrus neural progenitor cells. The protein-A eluates from depressed or non-depressed, diabetic patients were injected (via intracerebroventricular route) into mice and 7-10 days later behavioral tests (sucrose preference, and tail suspension tests) were conducted to determine whether the autoantibodies induced anhedonia or despair.</p><p><strong>Results: </strong>Diabetic depression (n=20) autoantibodies caused a significant inhibition of PC12 cell neurite outgrowth (<i>P<0.001</i>) or endothelial cell proliferation compared to autoantibodies in control, diabetic (n=20) or non-diabetic (n=10) patients without depression. Process extension and survival in adult rat dentate gyrus neural progenitor cells was significantly reduced (<i>P<0.001</i>) by diabetic depression autoantibodies (n= 11) compared to the effects from similar concentrations (5-7 μg/mL) of autoantibodies in diabetic (n=12) or non-diabetic patients without depression (n=7). Ten micromolar concentrations of Y27632, a selective Rho-Associated Protein Kinase (ROCK) inhibitor, significantly prevented (<i>P<0.0001</i>) neural progenitor cell process retraction induced by diabetes depression autoantibodies (n=5). Mice treated with diabetic depression autoantibodies (n=16 from two different patients' autoantibodies) exhibited significantly reduced (<i>P=0.027</i>) sucrose preference (anhedonia) compared to mice treated with diabetic control autoantibodies (n=16 from two different patients' autoantibodies).</p><p><strong>Conclusion: </strong>These data suggest that autoantibodies in a subset of older adult diabetic depression inhibit endothelial cell survival, and impair process extension and survival in adult dentate gyrus neural progenitor cells <i>in vitro.</i></p>","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963887/pdf/nihms967347.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9603699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telemedicine and Diabetic Retinopathy: Review of Published Screening Programs.","authors":"Kevin Tozer,&nbsp;Maria A Woodward,&nbsp;Paula A Newman-Casey","doi":"10.15226/2374-6890/2/4/00131","DOIUrl":"https://doi.org/10.15226/2374-6890/2/4/00131","url":null,"abstract":"<p><strong>Background: </strong>Diabetic Retinopathy (DR) is a leading cause of blindness worldwide even though successful treatments exist. Improving screening and treatment could avoid many cases of vision loss. However, due to an increasing prevalence of diabetes, traditional in-person screening for DR for every diabetic patient is not feasible. Telemedicine is one viable solution to provide high-quality and efficient screening to large number of diabetic patients.</p><p><strong>Purpose: </strong>To provide a narrative review of large DR telemedicine screening programs.</p><p><strong>Methods: </strong>Articles were identified through a comprehensive search of the English-language literature published between 2000 and 2014. Telemedicine screening programs were included for review if they had published data on at least 150 patients and had available validation studies supporting their model. Screening programs were then categorized according to their American Telemedicine Association Validation Level.</p><p><strong>Results: </strong>Seven programs from the US and abroad were identified and included in the review. Three programs were Category 1 programs (Ophdiat, EyePacs, and Digiscope), two were Category 2 programs (Eye Check, NHS Diabetic Eye Screening Program), and two were Category 3 programs (Joslin Vision Network, Alberta Screening Program). No program was identified that claimed category 4 status. Programs ranged from community or city level programs to large nationwide programs including millions of individuals. The programs demonstrated a high level of clinical accuracy in screening for DR. There was no consensus amongst the programs regarding the need for dilation, need for stereoscopic images, or the level of training for approved image graders.</p><p><strong>Conclusion: </strong>Telemedicine programs have been clinically validated and successfully implemented across the globe. They can provide a high-level of clinical accuracy for screening for DR while improving patient access in a cost-effective and scalable manner.</p>","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942133/pdf/nihms799190.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34581652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topiramate Protects Pericytes from Glucotoxicity: Role for Mitochondrial CA VA in Cerebromicrovascular Disease in Diabetes.","authors":"Ping Patrick,&nbsp;Tulin O Price,&nbsp;Ana L Diogo,&nbsp;Nader Sheibani,&nbsp;William A Banks,&nbsp;Gul N Shah","doi":"10.15226/2374-6890/2/2/00123","DOIUrl":"https://doi.org/10.15226/2374-6890/2/2/00123","url":null,"abstract":"<p><p>Hyperglycemia in diabetes mellitus causes oxidative stress and pericyte depletion from the microvasculature of the brain thus leading to the Blood-Brain Barrier (BBB) disruption. The compromised BBB exposes the brain to circulating substances, resulting in neurotoxicity and neuronal cell death. The decline in pericyte numbers in diabetic mouse brain and pericyte apoptosis in high glucose cultures are caused by excess superoxide produced during enhanced respiration (mitochondrial oxidative metabolism of glucose). Superoxide is precursor to all Reactive Oxygen Species (ROS) which, in turn, cause oxidative stress. The rate of respiration and thus the ROS production is regulated by mitochondrial carbonic anhydrases (mCA) VA and VB, the two isoforms expressed in the mitochondria. Inhibition of both mCA: decreases the oxidative stress and restores the pericyte numbers in diabetic brain; and reduces high glucose-induced respiration, ROS, oxidative stress, and apoptosis in cultured brain pericytes. However, the individual role of the two isoforms has not been established. To investigate the contribution of mCA VA in ROS production and apoptosis, a mCA VA overexpressing brain pericyte cell line was engineered. These cells were exposed to high glucose and analyzed for the changes in ROS and apoptosis. Overexpression of mCA VA significantly increased pericyte ROS and apoptosis. Inhibition of mCA VA with topiramate prevented increases both in glucose-induced ROS and pericyte death. These results demonstrate, for the first time, that mCA VA regulates the rate of pericyte respiration. These findings identify mCA VA as a novel and specific therapeutic target to protect the cerebromicrovascular bed in diabetes.</p>","PeriodicalId":73731,"journal":{"name":"Journal of endocrinology and diabetes","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495916/pdf/nihms-699862.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33898709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}