Search results for "Insulin"

DRB1*0401-restricted human T cell clone specific for the major proinsulin73-90 epitope expresses a down-regulatory T helper 2 phenotype.

2006

Recently, we have identified proinsulin (P-Ins) 73-90 as an immunodominant T cell epitope of HLA-DRB1*0401 (DR4) subjects with β-islet cell autoimmunity and of HLA-DR4/CD4 double-transgenic mice immunized with human P-Ins. We have compared the fine specificities of one human CD4 T cell clone and two mouse T cell hybridoma clones recognizing this epitope, and, although these three clones all recognized the same core region (LALEGSLQK), there were major differences in how they interacted with the peptide (p)/HLA complex, reflecting the fact that human P-Ins is a foreign antigen in the mouse and an autoantigen in the type 1 diabetes patient. The human T cell clone was forkhead transcription f…

Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes.

2020

Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammatio…

Retinal neurodegenerative changes in the adult insulin receptor substrate-2 deficient mouse.

2014

Abstract Insulin receptor substrate-2 (Irs2) mediates peripheral insulin action and is essential for retinal health. Previous investigations have reported severe photoreceptor degeneration and abnormal visual function in Irs2-deficient mice. However, molecular changes in the Irs2 − / −  mouse retina have not been described. In this study, we examined retinal degenerative changes in neuronal and glial cells of adult (9- and 12-week old) Irs2 − / −  mice by immunohistochemistry. 9-week old Irs2 − / −  mice showed significant thinning of outer retinal layers, concomitant to Muller and microglial cell activation. Photoreceptor cells displayed different signs of degeneration, such as outer/inner…

Magnesium homeostasis and aging.

2010

Aging is very often associated with magnesium (Mg) deficit. Total plasma magnesium concentrations are remarkably constant in healthy subjects throughout life, while total body Mg and Mg in the intracellular compartment tend to decrease with age. Dietary Mg deficiencies are common in the elderly population. Other frequent causes of Mg deficits in the elderly include reduced Mg intestinal absorption, reduced Mg bone stores, and excess urinary loss. Secondary Mg deficit in aging may result from different conditions and diseases often observed in the elderly (i.e. insulin resistance and/or type 2 diabetes mellitus) and drugs (i.e. use of hypermagnesuric diuretics). Chronic Mg deficits have been…

The nucleotide and partial amino acid sequences of rat fetuin. Identity with the natural tyrosine kinase inhibitor of the rat insulin receptor.

1992

Fetuins are among the major plasma proteins, yet their biological role has remained elusive. Here we report the molecular cloning of rat fetuin and the sequence analysis of a full-length clone, RF619 of 1456 bp with an open reading frame of 1056 bp encoding 352 amino acid residues. The coding part of RF619 was identical with the cDNA sequence of the natural inhibitor of the insulin receptor tyrosine kinase from rat (pp63) except for four substitutions and a single base insertion causing divergence of the predicted protein sequences. Partial amino acid sequences of rat plasma fetuin were in agreement with the predictions based on the RF619 cDNA. Purified rat fetuin inhibited the insulin rece…

Endotoxaemia resulting from decreased serotonin tranporter (5-HTT) function: A reciprocal risk factor for depression and insulin resistance?

2015

International audience; Depression and diabetes are serious diseases with an increasing global prevalence. Intriguingly, recent meta-analyses have highlighted an asymmetrical relationship between the two conditions as depressed patients were found to display a higher risk of developing type 2 diabetes than those individuals suffering from diabetes are to become depressed. Based on recent findings, we favor a hypothesis where by decreased peripheral serotonin (5-HT) transporter (5-HTT) function is a reciprocal risk factor for the comorbidity of depression and diabetes, as it can trigger inflammatory pathogenetic mechanisms of both conditions. Higher intestinal levels of 5-HT and 5-HT3 recept…

ANP and insulin presence in human foetal pancreas

2009

Aim of this work is to investigate the presence of Atrial natriuretic peptide (ANP) and insulin in human foetal pancreas from not diabetic and diabetic mothers. The data literature evidenced that relationship between serum ANP and insulin. This work carried out on the sections immunostained for ANP and nsulin showed positivity for ANP and insulin in beta-cells of pancreas from diabetic mothers, while positivity for insulin in beta-cells of foetuses from not diabetic mothers. Results indicate that the insulin presence stimulates the ANP synthesis in pancreas of human foetuses from diabetic mothers. Aim of this work is to investigate the presence of Atrial natriuretic peptide (ANP) and insuli…

Immunolocalization of ANP and insulin in pancreas of human foetuses from diabetic mothers.

2009

ADIPOSE TISSUE-TARGETED STEM CELL TRANSPLANTATION FOR INSULIN RESISTANCE-RELATED CNS DEFICITS

Compelling evidence indicates that Type 2 Diabetes (T2D) and Alzheimer’s Disease (AD) may possibly share a common pathological origin, but the underlying mechanisms remain poorly understood. T2D is a known risk factor for AD and insulin resistance (hallmark of T2D) has been extensively documented in AD patients. Notably, insulin is important for learning and memory due to its role in LTP and LTD modulation. Adipose tissue (AT) dysfunction is a risk factor for T2D, in fact elevated levels of free fatty acids are prodromal to insulin resistance and have been reported in AD brains, as well. In this study, I used a mouse model (AtENPP1Tg mouse) that recapitulates typical characteristics of huma…

Insulin Nanogels: a New Strategy for the Treatment of Alzheimer’s Disease

2016

A growing body of evidence shows that Insulin, Insulin Receptor (IR) and IR signaling are involved in brain cognitive functions and their dysfunction is implicated in Alzheimer’s disease (AD) degeneration. Thus, administration of insulin could be a strategy for AD treatment. For this aim we have designed, synthesized and characterized a nanogel system (NG) to deliver insulin to the brain, as a tool for the development of a new therapy for AD. A carboxyl-functionalized poly(N-vinyl pyrrolidone) nanogel system produced by ionizing radiation was chosen as substrate for the covalent attachment of insulin or fluorescent molecules relevant for its characterization. Biocompatibility of the naked c…