Spatial Regulation of Reactive Oxygen Species via G6PD in Brown Adipocytes Supports Thermogenic Function
Reactive oxygen species (ROS) are associated with various roles of brown adipocytes. Glucose-6-phosphate dehydrogenase (G6PD) controls cellular redox potentials by producing NADPH. Although G6PD upregulates cellular ROS levels in white adipocytes, the roles of G6PD in brown adipocytes remain elusive. Here, we found that G6PD defect in brown adipocytes impaired thermogenic function through excessive cytosolic ROS accumulation. Upon cold exposure, G6PD-deficient mutant (G6PDmut) mice exhibited cold intolerance and downregulated thermogenic gene expression in brown adipose tissue (BAT). In addition, G6PD-deficient brown adipo...
Source: Diabetes - September 14, 2021 Category: Endocrinology Source Type: research
Coxsackievirus B Vaccines Prevent Infection-Accelerated Diabetes in NOD Mice and Have No Disease-Inducing Effect
Enteroviruses, including the Coxsackievirus Bs (CVB), have been implicated as causal agents in human type 1 diabetes. Immunization of at-risk individuals with a CVB vaccine provides an attractive strategy for elucidating the role of CVBs in the disease etiology. Previously, we have shown that an inactivated whole-virus vaccine covering all CVB serotypes (CVB1 –6) is safe to administer and highly immunogenic in preclinical models, including nonhuman primates. Before initiating clinical trials with this type of vaccine, it was also important to address1) whether the vaccine itself induces adverse immune reactions, includin...
Source: Diabetes - September 8, 2021 Category: Endocrinology Source Type: research
Chromogranin A Deficiency Confers Protection From Autoimmune Diabetes via Multiple Mechanisms
Recognition of β-cell antigens by autoreactive T cells is a critical step in the initiation of autoimmune type1 diabetes. A complete protection from diabetes development in NOD mice harboring a point mutation in the insulin B-chain 9–23 epitope points to a dominant role of insulin in diabetogenesis. Generation of NOD mice lacking the chromogranin A protein (NOD.ChgA−/−) completely nullified the autoreactivity of the BDC2.5 T cell and conferred protection from diabetes onset. These results raised the issue concerning the dominant antigen that drives the autoimmune process. Here we revisited the NOD.ChgA−/− mice a...
Source: Diabetes - September 8, 2021 Category: Endocrinology Source Type: research
Multicomponent Plasmid Protects Mice From Spontaneous Autoimmune Diabetes
Type 1 diabetes is an autoimmune disease in which insulin-secreting β-cells are destroyed, leading to a lifelong dependency on exogenous insulin. There are no approved disease-modifying therapies available, and future immunotherapies would need to avoid generalized immune suppression. We developed a novel plasmid expressing preproinsulin2 and a combination of immun omodulatory cytokines (transforming growth factor-β1, interleukin [IL]-10, and IL-2) capable of near-complete prevention of autoimmune diabetes in nonobese diabetic mice. Efficacy depended on preproinsulin2, suggesting antigen-specific tolerization, and on the...
Source: Diabetes - August 13, 2021 Category: Endocrinology Source Type: research
Issues and Events
(Source: Diabetes)
Source: Diabetes - October 23, 2017 Category: Endocrinology Tags: Issues and Events Source Type: research
Haptoglobin 1-1 Genotype Modulates the Association of Glycemic Control With Hippocampal Volume in Elderly Individuals With Type 2 Diabetes
Recent evidence suggests that glycemic control is associated with cognitive function in older patients with type 2 diabetes who are carriers of the haptoglobin (Hp) 1-1 genotype compared with noncarriers. We assessed whether poor glycemic control in Hp 1-1 carriers is more strongly associated with smaller hippocampal volume than in noncarriers. Hippocampal volume was generated from high-resolution structural T1 MRI obtained for 224 participants (28 Hp 1-1 carriers [12.5%] and 196 noncarriers [87.5%]) from the Israel Diabetes and Cognitive Decline (IDCD) study, who had a mean (SD) number of years in the Maccabi Healthcare S...
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Livny, A.; Ravona-Springer, R.; Heymann, A.; Priess, R.; Kushnir, T.; Tsarfaty, G.; Rabinov, L.; Moran, R.; Tik, N.; Moshier, E.; Cooper, I.; Greenbaum, L.; Silverman, J.; Levy, A.; Sano, M.; Bendlin, B. B.; Buchman, A. S.; Schnaider-Beeri, M. Tags: Genetics-Type 2 Diabetes Genetics/Genomes/Proteomics/Metabolomics Source Type: research
A Mendelian Randomization Study of Metabolite Profiles, Fasting Glucose, and Type 2 Diabetes
Mendelian randomization (MR) provides us the opportunity to investigate the causal paths of metabolites in type 2 diabetes and glucose homeostasis. We developed and tested an MR approach based on genetic risk scoring for plasma metabolite levels, utilizing a pathway-based sensitivity analysis to control for nonspecific effects. We focused on 124 circulating metabolites that correlate with fasting glucose in the Erasmus Rucphen Family (ERF) study (n = 2,564) and tested the possible causal effect of each metabolite with glucose and type 2 diabetes and vice versa. We detected 14 paths with potential causal effects by MR, foll...
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Liu, J.; van Klinken, J. B.; Semiz, S.; van Dijk, K. W.; Verhoeven, A.; Hankemeier, T.; Harms, A. C.; Sijbrands, E.; Sheehan, N. A.; van Duijn, C. M.; Demirkan, A. Tags: Genetics-Type 2 Diabetes Genetics/Genomes/Proteomics/Metabolomics Source Type: research
A Loss-of-Function Splice Acceptor Variant in IGF2 Is Protective for Type 2 Diabetes
Type 2 diabetes (T2D) affects more than 415 million people worldwide, and its costs to the health care system continue to rise. To identify common or rare genetic variation with potential therapeutic implications for T2D, we analyzed and replicated genome-wide protein coding variation in a total of 8,227 individuals with T2D and 12,966 individuals without T2D of Latino descent. We identified a novel genetic variant in the IGF2 gene associated with ~20% reduced risk for T2D. This variant, which has an allele frequency of 17% in the Mexican population but is rare in Europe, prevents splicing between IGF2 exons 1 and 2. We sh...
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Mercader, J. M.; Liao, R. G.; Bell, A. D.; Dymek, Z.; Estrada, K.; Tukiainen, T.; Huerta-Chagoya, A.; Moreno-Macias, H.; Jablonski, K. A.; Hanson, R. L.; Walford, G. A.; Moran, I.; Chen, L.; Agarwala, V.; Ordonez-Sanchez, M. L.; Rodriguez-Guillen, R.; Rod Tags: Genetics-Type 2 Diabetes Genetics/Genomes/Proteomics/Metabolomics Source Type: research
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10–8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associa...
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Scott, R. A.; Scott, L. J.; Mägi, R.; Marullo, L.; Gaulton, K. J.; Kaakinen, M.; Pervjakova, N.; Pers, T. H.; Johnson, A. D.; Eicher, J. D.; Jackson, A. U.; Ferreira, T.; Lee, Y.; Ma, C.; Steinthorsdottir, V.; Thorleifsson, G.; Qi, L.; Van Zuydam, Tags: Genetics-Type 2 Diabetes Genetics/Genomes/Proteomics/Metabolomics Source Type: research
Inhibition of 12/15-Lipoxygenase Protects Against {beta}-Cell Oxidative Stress and Glycemic Deterioration in Mouse Models of Type 1 Diabetes
Islet β-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-Lipoxygenase (12/15-LOX) is induced in β-cells and macrophages during T1D and produces proinflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency. Only ML351 exhibited no ap...
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Hernandez-Perez, M.; Chopra, G.; Fine, J.; Conteh, A. M.; Anderson, R. M.; Linnemann, A. K.; Benjamin, C.; Nelson, J. B.; Benninger, K. S.; Nadler, J. L.; Maloney, D. J.; Tersey, S. A.; Mirmira, R. G. Tags: Islet Biology-Apoptosis Pharmacology and Therapeutics Source Type: research
Long-term Hyperglycemia Naturally Induces Dental Caries but Not Periodontal Disease in Type 1 and Type 2 Diabetic Rodents
In conclusion, long-term hyperglycemia naturally induces dental caries but not PD in type 1 and type 2 diabetic rodents. (Source: Diabetes)
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Nakahara, Y.; Ozaki, K.; Matsuura, T. Tags: Diabetes Education Complications Source Type: research
Pancreatic {beta}-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation
Pancreatic islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these "isletokines" in health and disease is largely unknown. We observed that islets release multiple inflammatory mediators in patients undergoing islet transplants within hours of infusion. The proinflammatory cytokine interferon-–induced protein 10 (IP-10/CXCL10) was among the highest released, and high levels correlated with poor islet transplant outcomes. Transgenic mouse studies confirmed that donor islet–specific expression of IP-10 contributed to islet inflammation ...
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Yoshimatsu, G.; Kunnathodi, F.; Saravanan, P. B.; Shahbazov, R.; Chang, C.; Darden, C. M.; Zurawski, S.; Boyuk, G.; Kanak, M. A.; Levy, M. F.; Naziruddin, B.; Lawrence, M. C. Tags: Islet Biology-Signal Transduction Immunology and Transplantation Source Type: research
The Myokine Irisin Is Released in Response to Saturated Fatty Acids and Promotes Pancreatic {beta}-Cell Survival and Insulin Secretion
In conclusion, irisin can promote β-cell survival and enhance GSIS and may thus participate in the communication between skeletal muscle and β-cells under conditions of excess saturated fatty acids. (Source: Diabetes)
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Natalicchio, A.; Marrano, N.; Biondi, G.; Spagnuolo, R.; Labarbuta, R.; Porreca, I.; Cignarelli, A.; Bugliani, M.; Marchetti, P.; Perrini, S.; Laviola, L.; Giorgino, F. Tags: Integrated Physiology-Other Hormones Islet Studies Source Type: research
Atrial Natriuretic Peptide Affects Stimulus-Secretion Coupling of Pancreatic {beta}-Cells
Atrial natriuretic peptide (ANP) influences glucose homeostasis and possibly acts as a link between the cardiovascular system and metabolism, especially in metabolic disorders like diabetes. The current study evaluated effects of ANP on β-cell function by the use of a β-cell–specific knockout of the ANP receptor with guanylate cyclase activity (βGC-A-KO). ANP augmented insulin secretion at the threshold glucose concentration of 6 mmol/L and decreased KATP single-channel activity in β-cells of control mice but not of βGC-A-KO mice. In wild-type β-cells but not β-cells lacking functio...
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Undank, S.; Kaiser, J.; Sikimic, J.; Düfer, M.; Krippeit-Drews, P.; Drews, G. Tags: Islet Biology-Signal Transduction Islet Studies Source Type: research
Defining a Novel Role for the Pdx1 Transcription Factor in Islet {beta}-Cell Maturation and Proliferation During Weaning
The transcription factor encoded by the Pdx1 gene is a critical transcriptional regulator, as it has fundamental actions in the formation of all pancreatic cell types, islet β-cell development, and adult islet β-cell function. Transgenic- and cell line–based experiments have identified 5'-flanking conserved sequences that control pancreatic and β-cell type–specific transcription, which are found within areas I (bp –2694 to –2561), II (bp –2139 to –1958), III (bp –1879 to –1799), and IV (bp –6200 to –5670). Because of the presence in area IV of bindi...
Source: Diabetes - October 23, 2017 Category: Endocrinology Authors: Spaeth, J. M.; Gupte, M.; Perelis, M.; Yang, Y.-P.; Cyphert, H.; Guo, S.; Liu, J.-H.; Guo, M.; Bass, J.; Magnuson, M. A.; Wright, C.; Stein, R. Tags: Islet Biology-Beta Cell-Development and Postnatal Growth Islet Studies Source Type: research
