Search results for " Type 1"
showing 10 items of 430 documents
Enhanced Lipid Peroxidation and Platelet Activation in the Early Phase of Type 1 Diabetes Mellitus
2003
Background— To investigate early events possibly related to the development of diabetic angiopathy, we examined whether 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) formation, a marker of in vivo oxidant stress, is altered in different stages of type 1 diabetes (T1DM) and whether it correlates with the rate of thromboxane (TX) A 2 biosynthesis, a marker of in vivo platelet activation. We also investigated the relationship between inflammatory markers and F 2 -isoprostane formation in this setting. Methods and Results— A cross-sectional study was performed in 23 insulin-treated patients aged <18 years with new-onset T1DM (≤6 weeks, group A), matched for age and gender with 23 patients with s…
The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
2021
Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiati…
Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease
2021
Abstract Context We previously presented evidence that TSH receptor (TSHR)-stimulating autoantibodies (TSAbs) bind to and activate TSHRs but do not bind to IGF1 receptors (IGF1Rs). Nevertheless, we showed that IGF1Rs were involved in thyroid eye disease (TED) pathogenesis because TSAbs activated crosstalk between TSHR and IGF1R. Teprotumumab, originally generated to inhibit IGF1 binding to IGF1R, was recently approved for the treatment of TED (Tepezza). Objective To investigate the role of TSHR/IGF1R crosstalk in teprotumumab treatment of TED. Design We used orbital fibroblasts from patients with TED (TEDOFs) and measured stimulated hyaluronan (HA) secretion as a measure of orbital fibrobla…
Effects of combined hormone replacement therapy or its effective agents on the IGF-1 pathway in skeletal muscle.
2010
Objectives To investigate the effects of combined hormone replacement therapy (HRT) and its effective agents on the IGF-1 signaling pathway. Design and methods To examine the effects of HRT on skeletal muscle in vivo, we utilized pre- and post-intervention samples from a randomized double blinded trial with 50–57-year-old women. The intervention included the year-long use of either HRT preparation (2 mg 17β-estradiol, E2; 1 mg norethisterone acetate, NETA, n = 10) or placebo (CO, n = 9). Microarray technology and quantitative PCR (qPCR) were used to study the expression of insulin-like growth factor I (IGF-1) and its splice variants as well as IGF-1 receptor, Akt1, mTOR, FOXO1, FOXO3, atrog…
Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis
2012
Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review the series of 54 distinct mutations identified in 48 unrelated families. Most of them are no…
IgG anti-endothelial cell antibodies (AECA) in type I diabetes mellitus; induction of adhesion molecule expression in cultured endothelial cells
1998
SUMMARYAECA were detected in 25 of 71 patients with type 1 diabetes mellitus and in two of 33 healthy subjects. Patients with diabetes of &lt; 1 year duration and those with long-standing disease had the highest levels of these antibodies. Inhibition studies suggest that at least part of the AECA reactivity is due to cross-reactive anti-ssDNA antibodies. AECA-positive sera were able to increase intercellular adhesion molecule-1 (ICAM-1) and E-selectin on human umbilical vein endothelial cells (HUVEC). Increased binding of polymorphonuclear (PMN) cells was also found to accompany raised E-selectin expression. Soluble ICAM-1 and E-selectin were also found to be increased in the sera of AE…
AT1 Receptor Gene Polymorphisms in relation to Postprandial Lipemia
2011
Background. Recent data suggest that the renin-angiotensin system may be involved in triglyceride (TG) metabolism. We explored the effect of the common A1166C and C573T polymorphisms of the angiotensin II type 1 receptor (AT1R) gene on postprandial lipemia.Methods. Eighty-two subjects measured daytime capillary TG, and postprandial lipemia was estimated as incremental area under the TG curve. The C573T and A1166C polymorphisms of the AT1R gene were determined.Results. Postprandial lipemia was significantly higher in homozygous carriers of the 1166-C allele (9.39±8.36 mM*h/L) compared to homozygous carriers of the 1166-A allele (2.02±6.20 mM*h/L) (P<0.05). Postprandial lipemia was similar…
Experiences with Blockade of the Renin System in Human Hypertension Using Converting Enzyme Inhibitor SQ 20,881 and Saralasin
1980
The development of agents which are capable of producing in vivo angiotensin II blockade has provided to investigators and clinicians alike the opportunity to determine and to quantify the extent to which the renin-angiotensin system participates in the maintenance of hypertensive states. High levels of plasma renin activity relative to the state of sodium balance have been documented in patients with malignant, surgically remediable renovascular hypertension and also in some patients with essential hypertension.1 The recent development of the angiotensin II analogue sar1-ala8-angiotensin II (saralasin) provided evidence to support the concept that these elevated renin levels are in fact pa…
Neprilysin inhibition, endorphin dynamics, and early symptomatic improvement in heart failure: a pilot study
2020
Altres ajuts: This work was supported in part by Fundació La Marató de TV3 (201516-10, 201502-30), Societat Catalana de Cardiologia, "la Caixa" Banking Foundation. Altres ajuts: PERIS/SLT002-16-00234 Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor developed for the treatment of heart failure with reduced ejection fraction. Its benefits are achieved through the inhibition of neprilysin (NEP) and the specific blockade of the angiotensin receptor AT1. The many peptides metabolized by NEP suggest multifaceted potential consequences of its inhibition. We sought to evaluate the short-term changes in serum endorphin (EP) values and their relation with patients' p…
Oxidative stress and endothelial dysfunction: therapeutic implications.
2011
In a previous issue of Annals of Medicine, we presented evidence in support of the concept that an abnormally increased production of reactive oxygen species plays a central role in the genesis and progression of cardiovascular disease. While a number of preclinical lines of evidence support this concept, and despite the results of many studies suggesting a beneficial impact of antioxidant drugs on endothelial function, large clinical trials have failed to demonstrate a benefit of antioxidants on cardiovascular outcomes. Studies exploring the possibility that classical antioxidants such as vitamin C, vitamin E, selenium, or folic acid may improve the prognosis of patients with cardiac disea…