In This Issue of Diabetes
(Source: Diabetes)
Source: Diabetes - May 22, 2017 Category: Endocrinology Tags: In This Issue Source Type: research
Issues and Events
(Source: Diabetes)
Source: Diabetes - April 20, 2017 Category: Endocrinology Tags: Issues and Events Source Type: research
Statement of Retraction. The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes. Diabetes 2010;59:1870-1878. DOI: 10.2337/db09-1503. PMID: 20460426
(Source: Diabetes)
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Boström, P.; Andersson, L.; Vind, B.; Haversen, L.; Rutberg, M.; Wickström, Y.; Larsson, E.; Jansson, P.-A.; Svensson, M. K.; Branemark, R.; Ling, C.; Beck-Nielsen, H.; Boren, J.; Hojlund, K.; Olofsson, S.-O. Tags: Statement of Retraction Source Type: research
Genetics of Type 2 Diabetes in U.S. Hispanic/Latino Individuals: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in U.S. Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2,499 T2D case subjects and 5,247 control subjects from six Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance levels. Conditional analysis on known index single nucleotide polymorphisms (SNPs) indicated an additional independent signal at KCNQ1, represented by an African ancestry&...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Qi, Q.; Stilp, A. M.; Sofer, T.; Moon, J.-Y.; Hidalgo, B.; Szpiro, A. A.; Wang, T.; Ng, M. C. Y.; Guo, X.; MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium; Chen, Y.-D. I.; Taylor, K. D.; Aviles-Santa, M. L.; Papanicolaou, G.; Pank Tags: Genetics/Genomes/Proteomics/Metabolomics Source Type: research
Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice
In conclusion, butyrate and its more palatable synthetic derivative, FBA, modulating mitochondrial function, efficiency, and dynamics, can be considered a new therapeutic strategy to counteract obesity and insulin resistance. (Source: Diabetes)
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Mollica, M. P.; Mattace Raso, G.; Cavaliere, G.; Trinchese, G.; De Filippo, C.; Aceto, S.; Prisco, M.; Pirozzi, C.; Di Guida, F.; Lama, A.; Crispino, M.; Tronino, D.; Di Vaio, P.; Berni Canani, R.; Calignano, A.; Meli, R. Tags: Pharmacology and Therapeutics Source Type: research
Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy
Efficient biomarkers for diabetic nephropathy (DN) have not been established. Using ELISA, we found previously that urinary levels of full-length megalin (C-megalin), a multiligand endocytic receptor in proximal tubules, was positively correlated with DN progression in patients with type 2 diabetes mellitus (T2DM). Here, we found that urinary extracellular vesicle (UEV) excretion and C-megalin content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in patients with T2DM. Cultured immortalized rat proximal tubule cells (IRPTCs) treated with fatty acid–free BSA or ad...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: De, S.; Kuwahara, S.; Hosojima, M.; Ishikawa, T.; Kaseda, R.; Sarkar, P.; Yoshioka, Y.; Kabasawa, H.; Iida, T.; Goto, S.; Toba, K.; Higuchi, Y.; Suzuki, Y.; Hara, M.; Kurosawa, H.; Narita, I.; Hirayama, Y.; Ochiya, T.; Saito, A. Tags: Complications Source Type: research
Spinal Disinhibition in Experimental and Clinical Painful Diabetic Neuropathy
Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal -aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin sup...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Marshall, A. G.; Lee-Kubli, C.; Azmi, S.; Zhang, M.; Ferdousi, M.; Mixcoatl-Zecuatl, T.; Petropoulos, I. N.; Ponirakis, G.; Fineman, M. S.; Fadavi, H.; Frizzi, K.; Tavakoli, M.; Jeziorska, M.; Jolivalt, C. G.; Boulton, A. J. M.; Efron, N.; Calcutt, N. A.; Tags: Complications Source Type: research
Nonsuppressed Glucagon After Glucose Challenge as a Potential Predictor for Glucose Tolerance
Glucagon levels are classically suppressed after glucose challenge. It is still not clear as to whether a lack of suppression contributes to hyperglycemia and thus to the development of diabetes. We investigated the association of postchallenge change in glucagon during oral glucose tolerance tests (OGTTs), hypothesizing that higher postchallenge glucagon levels are observed in subjects with impaired glucose tolerance (IGT). Glucagon levels were measured during OGTT in a total of 4,194 individuals without diabetes in three large European cohorts. Longitudinal changes in glucagon suppression were investigated in 50 particip...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Wagner, R.; Hakaste, L. H.; Ahlqvist, E.; Heni, M.; Machann, J.; Schick, F.; Van Obberghen, E.; Stefan, N.; Gallwitz, B.; Tuomi, T.; Häring, H.-U.; Groop, L.; Fritsche, A. Tags: Pathophysiology Source Type: research
Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules
In this study, we tested the hypothesis that autophagy could contribute to the degradation of AGEs in the diabetic kidney by modulating lysosomal biogenesis. Both a high-glucose and exogenous AGE overload gradually blunted autophagic flux in the cultured PTECs. AGE overload upregulated lysosomal biogenesis and function in vitro, which was inhibited in autophagy-deficient PTECs because of the impaired nuclear translocation of transcription factor EB. Consistently, streptozotocin-treated, PTEC-specific, autophagy-deficient mice failed to upregulate lysosomal biogenesis and exhibited the accumulation of AGEs in the glomeruli ...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Takahashi, A.; Takabatake, Y.; Kimura, T.; Maejima, I.; Namba, T.; Yamamoto, T.; Matsuda, J.; Minami, S.; Kaimori, J.-y.; Matsui, I.; Matsusaka, T.; Niimura, F.; Yoshimori, T.; Isaka, Y. Tags: Pathophysiology Source Type: research
Hyperglycemia-Induced Changes in ZIP7 and ZnT7 Expression Cause Zn2+ Release From the Sarco(endo)plasmic Reticulum and Mediate ER Stress in the Heart
Changes in cellular free Zn2+ concentration, including those in the sarco(endo)plasmic reticulum [S(E)R], are primarily coordinated by Zn2+ transporters (ZnTs) whose identity and role in the heart are not well established. We hypothesized that ZIP7 and ZnT7 transport Zn2+ in opposing directions across the S(E)R membrane in cardiomyocytes and that changes in their activity play an important role in the development of ER stress during hyperglycemia. The subcellular S(E)R localization of ZIP7 and ZnT7 was determined in cardiomyocytes and in isolated S(E)R preparations. Markedly increased mRNA and protein levels of ZIP7 were o...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Tuncay, E.; Bitirim, V. C.; Durak, A.; Carrat, G. R. J.; Taylor, K. M.; Rutter, G. A.; Turan, B. Tags: Pathophysiology Source Type: research
Increase in Pancreatic Proinsulin and Preservation of {beta}-Cell Mass in Autoantibody-Positive Donors Prior to Type 1 Diabetes Onset
Type 1 diabetes is characterized by the loss of insulin production caused by β-cell dysfunction and/or destruction. The hypothesis that β-cell loss occurs early during the prediabetic phase has recently been challenged. Here we show, for the first time in situ, that in pancreas sections from autoantibody-positive (Ab+) donors, insulin area and β-cell mass are maintained before disease onset and that production of proinsulin increases. This suggests that β-cell destruction occurs more precipitously than previously assumed. Indeed, the pancreatic proinsulin-to-insulin area ratio was also increased in thes...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Rodriguez-Calvo, T.; Zapardiel-Gonzalo, J.; Amirian, N.; Castillo, E.; Lajevardi, Y.; Krogvold, L.; Dahl-Jorgensen, K.; von Herrath, M. G. Tags: Pathophysiology Source Type: research
Cardiac Autonomic Regulation and Repolarization During Acute Experimental Hypoglycemia in Type 2 Diabetes
We examined changes in cardiac autonomic function and repolarization during sustained experimental hypoglycemia. Twelve adults with T2DM and 11 age- and BMI-matched control participants without diabetes underwent paired hyperinsulinemic clamps separated by 4 weeks. Glucose was maintained at euglycemia (6.0 mmol/L) or hypoglycemia (2.5 mmol/L) for 1 h. Heart rate, blood pressure, and heart rate variability were assessed every 30 min and corrected QT intervals and T-wave morphology every 60 min. Heart rate initially increased in participants with T2DM but then fell toward baseline despite maintained hypoglycemia at 1 h accom...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Chow, E.; Bernjak, A.; Walkinshaw, E.; Lubina-Solomon, A.; Freeman, J.; Macdonald, I. A.; Sheridan, P. J.; Heller, S. R. Tags: Pathophysiology Source Type: research
Cotransplantation of Mesenchymal Stem Cells With Neonatal Porcine Islets Improve Graft Function in Diabetic Mice
Mesenchymal stem cells (MSCs) possess immunoregulatory, anti-inflammatory, and proangiogenic properties and, therefore, have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow–derived MSCs have on neonatal porcine islets (NPIs) in vitro and determined islet engraftment and metabolic outcomes when cotransplanted in a mouse model. NPIs cocultured with MSCs had greater cellular insulin content and increased glucose-stimulated insulin secretion. NPIs were cotransplanted with or without MSCs in diabetic B6.129S7-Rag1tm1Mom/J mice. Blood glucose and weight were monitored until...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Hayward, J. A.; Ellis, C. E.; Seeberger, K.; Lee, T.; Salama, B.; Mulet-Sierra, A.; Kuppan, P.; Adesida, A.; Korbutt, G. S. Tags: Immunology and Transplantation Source Type: research
Local Sphingosine Kinase 1 Activity Improves Islet Transplantation
Pancreatic islet transplantation is a promising clinical treatment for type 1 diabetes, but success is limited by extensive β-cell death in the immediate posttransplant period and impaired islet function in the longer term. Following transplantation, appropriate vascular remodeling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase (SK) pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown. We observed that donor islets from mice deficient in SK1 (Sphk1 knockout) contain a reduced number of resident intrai...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Rojas-Canales, D.; Penko, D.; Myo Min, K. K.; Parham, K. A.; Peiris, H.; Haberberger, R. V.; Pitson, S. M.; Drogemuller, C.; Keating, D. J.; Grey, S. T.; Coates, P. T.; Bonder, C. S.; Jessup, C. F. Tags: Immunology and Transplantation Source Type: research
Mafa Enables Pdx1 to Effectively Convert Pancreatic Islet Progenitors and Committed Islet {alpha}-Cells Into {beta}-Cells In Vivo
Among the therapeutic avenues being explored for replacement of the functional islet β-cell mass lost in type 1 diabetes (T1D), reprogramming of adult cell types into new β-cells has been actively pursued. Notably, mouse islet α-cells will transdifferentiate into β-cells under conditions of near β-cell loss, a condition similar to T1D. Moreover, human islet α-cells also appear to poised for reprogramming into insulin-positive cells. Here we have generated transgenic mice conditionally expressing the islet β-cell–enriched Mafa and/or Pdx1 transcription factors to examine their pote...
Source: Diabetes - April 20, 2017 Category: Endocrinology Authors: Matsuoka, T.-a.; Kawashima, S.; Miyatsuka, T.; Sasaki, S.; Shimo, N.; Katakami, N.; Kawamori, D.; Takebe, S.; Herrera, P. L.; Kaneto, H.; Stein, R.; Shimomura, I. Tags: Islet Studies Source Type: research
