Juan Pablo Diez - Academia.edu (original) (raw)

Papers by Juan Pablo Diez

Journal of Biological Chemistry, 1993

Isolated connexin-32s from rat and mouse liver are proteolyzed in vitro by the intracellular Ca2+... more Isolated connexin-32s from rat and mouse liver are proteolyzed in vitro by the intracellular Ca2+-dependent neutral proteases, p-calpain and m-calpain, producing a major fragment of 26 kDa. Connexin-26 is not proteolyzed by calpain. Calpain cleaves connexin-32 at its C-terminal end as shown by '261-calmodulin binding experiments. Connexin-32, but not connexin-26, is phosphorylated by both protein kinase A and protein kinase C in serine residues and the sites of phosphorylation by both kinases remain in the major 26-kDa fragment resulting from calpain proteolysis. Phosphorylation of connexin-32 by protein kinase C, but not by protein kinase A, prevents the proteolytic attack of p-calpain and m-calpain. Phosphorylation of connexin-32 by protein kinase A and protein kinase C does not prevent its proteolysis by papain, a-chymotrypsin, proteinase K, and trypsin.

Endocrinología y Nutrición, 2005

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Medicina clínica, Jan 6, 1998

Advances in peritoneal dialysis. Conference on Peritoneal Dialysis, 2002

Atherosclerosis is an important cause of morbidity and mortality in peritoneal dialysis (PD) pati... more Atherosclerosis is an important cause of morbidity and mortality in peritoneal dialysis (PD) patients. Oxidative stress plays a role in the pathogenesis of uremic atherosclerosis. Although antioxidant substances (vitamins A and E) are elevated in the plasma of dialysis patients, intracellular and clinical signs of hypovitaminosis are frequently found. Recently, the importance of vitamin/carrier complexes as a marker of vitamin bioavailability has been demonstrated. In the present study, we analyzed vitamin A and E bioavailability, measured as vitamin/carrier complexes, and the relationship of those measurements with clinical atherosclerosis status in PD patients. We studied 45 patients (15 men, 30 women), who were divided into four groups according to clinical atherosclerotic score (CAS). Five cases were scored as CAS grade 1 (low CAS); 9 as CAS-2; 18 as CAS-3; and 13 as CAS-4. Vitamins A and E and their carriers [prealbumin and retinol binding protein (vitamin A), and cholesterol a...

Journal of thyroid research, 2012

Despite that thyroid cancer accounts for over 90% of tumors that arise from the endocrine system,... more Despite that thyroid cancer accounts for over 90% of tumors that arise from the endocrine system, these tumors barely represent 2% of solid tumors in adults. Many entities are grouped under the general term of thyroid cancer, and they differ in histological features as well as molecular and clinical behavior. Thus, the prognosis for patients with thyroid cancer ranges from a survival rate of >97% at 5 years, in the case of differentiated thyroid tumors sensitive to radioactive iodine, to a 4-month median survival for anaplastic tumors. The high vascularity in these tumors and the important role that oncogenic mutations may have in the RAS/RAF/MEK pathway and oncogenicity (as suggested by activating mutations and rearrangements of the RET gene) have led to the development of multitarget inhibitors in different histological subgroups of patients. The correct molecular characterization of patients with thyroid cancer is thought to be a key aspect for the future clinical management o...

European journal of endocrinology / European Federation of Endocrine Societies, 2006

Type 2 diabetes is a well recognised cause of chronic renal failure (CRF). Only few oral antidiab... more Type 2 diabetes is a well recognised cause of chronic renal failure (CRF). Only few oral antidiabetic drugs can be used for treating type 2 diabetes in patients with CRF. Among them are repaglinide, a rapid-acting prandial insulin releaser, and peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, such as rosiglitazone and pioglitazone. These compounds are metabolised in the liver, therefore accumulation of the drug and the risk of severe and prolonged hypoglycaemia are minimised. PPARgamma receptors are expressed in many tissues including the kidney. Recently, numerous healthful effects of PPARgamma agonists on several aspects related to renal function have been increasingly reported. These drugs have shown to possess many advantageous anti-inflammatory, haemodynamic, vascular and metabolic effects. In the present paper we have reviewed the more recent experimental studies that evaluated these potential beneficial effects of PPARgamma agonists on renal function and...

Medicina Clínica, 2015

Resumen Las recientes guias clinicas sobre disfuncion tiroidea y embarazo han cambiado la atencio... more Resumen Las recientes guias clinicas sobre disfuncion tiroidea y embarazo han cambiado la atencion sanitaria que se presta a la mujer gestante, pero sus recomendaciones estan en constante revision. Existe la necesidad de disponer de valores de referencia de la hormona estimulante del tiroides por trimestre y area geografica para el correcto diagnostico de disfuncion tiroidea. No hay dudas sobre la necesidad de tratamiento del hipotiroidismo franco, pero hay opiniones variables sobre el tratamiento del subclinico. Los efectos adversos de la hipotiroxinemia aislada y de la autoinmunidad tiroidea requieren nuevas investigaciones. Es fundamental diferenciar el hipertiroidismo por enfermedad de Graves del llamado hipertiroidismo gestacional transitorio, habitualmente autolimitado. Es importante reconocer los factores de riesgo para la tiroiditis posparto. Para evitar graves consecuencias en la descendencia, se recomienda mantener una adecuada nutricion de yodo durante el embarazo mediante suplementos de este oligoelemento. Continua la polemica sobre el cribado universal o selectivo de disfuncion tiroidea durante la gestacion, aunque las tendencias de algunas sociedades y de los ultimos estudios de coste-beneficio son favorables al cribado universal. Los estudios aleatorizados y controlados en desarrollo actualmente deberan reducir las incertidumbres que aun persisten en el area de la disfuncion tiroidea y el embarazo.

Proceedings of the National Academy of Sciences, 2010

Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear wha... more Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances the human β cell's sensitivity and responsiveness to glucose fluctuations. By using in situ hybridization, RT-PCR, immunohistochemistry, and Western blotting as well as recordings of cytoplasmic-free Ca 2+ concentration, [Ca 2+ ] i , and hormone release in vitro, we show that human β cells express ionotropic ATP receptors of the P2X 3 type and that activation of these receptors by ATP coreleased with insulin amplifies glucose-induced insulin secretion. Released ATP activates P2X 3 receptors in the β-cell plasma membrane, resulting in increased [Ca 2+ ] i and enhanced insulin secretion. Therefore, in human islets, released ATP forms a positive autocrine feedback loop that sensitizes the β cell's secretory machinery. This may explain how the human pancreatic β cell can respond so ef...

Journal of Medical Genetics, 2003

Journal of Histochemistry & Cytochemistry, 2009

The development of efficient, reproducible protocols for directed in vitro differentiation of hum... more The development of efficient, reproducible protocols for directed in vitro differentiation of human embryonic stem (hES) cells into insulin-producing β cells will benefit greatly from increased knowledge regarding the spatiotemporal expression profile of key instructive factors involved in human endocrine cell generation. Human fetal pancreases 7 to 21 weeks of gestational age, were collected following consent immediately after pregnancy termination and processed for immunostaining, in situ hybridization, and real-time RT-PCR expression analyses. Islet-like structures appear from approximately week 12 and, unlike the mixed architecture observed in adult islets, fetal islets are initially formed predominantly by aggregated insulin- or glucagon-expressing cells. The period studied (7–22 weeks) coincides with a decrease in the proliferation and an increase in the differentiation of the progenitor cells, the initiation of NGN3 expression, and the appearance of differentiated endocrine c...

The Journal of Clinical Endocrinology & Metabolism, 2004

European Journal of Human Genetics, 2002

Familial paraganglioma is a dominantly inherited disorder characterised by the development of hig... more Familial paraganglioma is a dominantly inherited disorder characterised by the development of highly vascular tumours in the head and neck. Recently, a relationship between hereditary tumours derived from the autonomic nervous system and germline mutations in the gene encoding succinate dehydrogenase complex subunit D (SDHD) is increasingly a subject of study. Familial paraganglioma syndrome is embryologically related to phaeochromocytoma, another neuroendocrine tumour that shows great aetiological and genetic heterogeneity. Some hereditary phaeochromocytomas may be associated with germline mutations in VHL, RET and NF1 genes in genetic disorders such as von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN 2) and neurofibromatosis type 1 (NF 1), respectively. However, there are many cases that cannot be explained by mutations in these genes. In this report, we describe two previously unreported mutations in two patients from 25 unrelated kindreds with phaeochromocytoma and/or paraganglioma disorders and with or without familial antecedents: a mutation featuring the change of tryptophan to a termination codon in exon 2, and a 4-bp deletion in exon 4 that results in a truncated protein. We also describe one missense substitution of uncertain significance. The patients had previously tested negative for germline mutations in VHL and RET genes and had not been previously selected. The involvement of SDHD mutations in familial phaeochromocytoma and/or paraganglioma predisposition is of considerable interest since other studies have shown these alterations to be associated with highly expressed angiogenic factors.

European Journal of Endocrinology, 2008

Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Convers... more Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Conversely, the kidney is not only an organ for metabolism and elimination of TH, but also a target organ of some of the iodothyronines' actions. Thyroid dysfunction causes remarkable changes in glomerular and tubular functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by a decrease in glomerular filtration, hyponatremia, and an alteration of the ability for water excretion. Excessive levels of TH generate an increase in glomerular filtration rate and renal plasma flow. Renal disease, in turn, leads to significant changes in thyroid function. The association of different types of glomerulopathies with both hyper- and hypofunction of the thyroid has been reported. Less frequently, tubulointerstitial disease has been associated with functional thyroid disorders. Nephrotic syndrome is accompanied by changes in the concentrations of TH due primarily to loss of protein...

European Journal of Endocrinology, 2003

Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific prot... more Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree...

Endocrine Journal, 2004

Generalized lipodystrophy is a rare disorder of adipose tissue, whose etiology remains unknown. P... more Generalized lipodystrophy is a rare disorder of adipose tissue, whose etiology remains unknown. Pathophysiology of this disorder is characterized by generalized loss of body fat associated with an infrequent form of diabetes mellitus (lipoatrophic diabetes). Main features of this form of diabetes mellitus are the severe insulin resistance and the absence of ketoacidosis. Lipodystrophy can be congenital or acquired. In the acquired form, metabolic disturbances usually begin in the first years of life and the response to conventional treatment is very poor. Some alterations in serum adipocytokines have been described in this disease. We report the case of a 74-year-old woman with acquired generalized lipodystrophy who presented with low-normal serum concentrations of leptin, low adiponectin and resistin levels, and high serum levels of TNFa. Patient was initially treated with fenofibrate, metformin and high doses of subcutaneous insulin achieving an adequate metabolic control. During this period, serum adipocytokines were periodically measured. We comment on the different etiopathogenic mechanisms and the therapeutic modalities of this rare syndrome.

Diabetes, 2001

Type 1 diabetes results from the autoimmune destruction of pancreatic β-cells in genetically susc... more Type 1 diabetes results from the autoimmune destruction of pancreatic β-cells in genetically susceptible individuals. Growing evidence suggests that genetically determined variation in the expression of self-antigens in thymus may affect the shaping of the T-cell repertoire and susceptibility to autoimmunity. For example, both allelic variation and parent-of-origin effects influence the thymic expression of insulin (a known type 1 diabetes autoantigen), and insulin gene transcription levels in thymus inversely correlate with susceptibility in both humans and transgenic models. It is unclear why patients lose tolerance to IA-2 (insulinoma-associated tyrosine phosphatase-like protein, or islet cell antigen 512 [ICA512]), especially because IA-2 polymorphisms are not associated with type 1 diabetes. We report that alternative splicing determines differential IA-2 expression in islets compared with thymus and spleen. Islets express full-length mRNA and two alternatively spliced transcri...

BMC Genomics, 2010

Background MicroRNAs are non-coding RNAs that regulate gene expression including differentiation ... more Background MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study. Results The microRNA signature of human fetal pancreatic samples 10-22 weeks of gestational age (wga), was obtained by PCR-based high throughput screening with Taqman Low Density Arrays. This method led to identification of 212 microRNAs. The microRNAs were classified in 3 groups: Group number I contains 4 microRNAs with the increasing profile; II, 35 microRNAs with decreasing profile and III with 173 microRNAs, which remain unchanged. We calculated Pearson correlations between the expression prof...

Atención Primaria, 2005

Agradecemos sinceramente a D. Antonio Hidalgo el interés demostrado por nuestro artículo. Palabra... more Agradecemos sinceramente a D. Antonio Hidalgo el interés demostrado por nuestro artículo. Palabras clave: Epidemiología. Medidas de resultados. Valoración de resultados.

Biochemical Journal, 1999

The biogenesis of connexins and their assembly into functional gap junction hemichannels (connexo... more The biogenesis of connexins and their assembly into functional gap junction hemichannels (connexons) was studied with the use of a cell-free transcription\translation system. Velocity sedimentation on sucrose gradients showed that a small proportion of connexin (Cx) 26 and Cx32 that were co-translationally translocated into microsomes were oligomers of Cx26 and Cx32. Chemical cross-linking studies showed that these corresponded to hexameric connexons. Reconstitution of connexons synthesized in itro into liposomes induced permeability properties consistent with the view that open gap junction hemichannels were produced. By using an immunoprecipitation approach, a simultaneous translation of Cx26 and Cx32 incorporated into microsomes resulted in homomeric connexons. However, supplementation of the translation system in itro with liver Golgi Abbreviations used : Cx, connexin ; DMS, dimethyl suberimidate ; DSP, dithiobispropionate ; DTT, dithiothreitol ; TEA, triethanolamine. 1 To whom correspondence should be addressed (e-mail wmbwhe!cardiff.ac.uk). membranes produced heteromeric connexons constructed of Cx32 and Cx26, and also resulted in an increased oligomerization especially of Cx32. All of the connexins analysed were inserted co-translationally into canine pancreatic microsomal membranes. In addition, Cx26 and Cx43, but not Cx32, were also inserted into microsomal membranes post-translationally. Analysis of various connexin constructs in which the cytoplasmic carboxy tails were transposed, the cytoplasmic tail of Cx43 was truncated or a reporter protein, aequorin, was attached to the C-terminus showed that tail length was not the major determinant of the post-translational membrane insertion of connexins.