Search results for "Insulin"
showing 10 items of 1360 documents
Induction of apoptosis in human retinoblastoma cells by topoisomerase inhibitors
1998
PURPOSE:To examine the apoptotic effect induced in human retinoblastoma Y79 cells by camptothecin, etoposide, and amsacrine, to examine the effect of these drugs on the expression of many apoptosis-related modulators, and to test the antiapoptotic effect exerted by insulin-like growth factor-I (IGF-I). METHODS:Morphologic features of apoptosis were demonstrated using acridine orange- ethidium bromide staining and electron microscopy. DNA fragmentation was determined by means of an in situ cell detection procedure (TdT-dUTP terminal nick-end labeling [TUNEL]) or by electrophoresis on agarose gels and was quantified by enzyme-linked immunosorbent assay. The expression of apoptosis-related mod…
Kinetics of different processes in human insulin amyloid formation.
2007
Human insulin has long been known to form amyloid fibrils under given conditions. The molecular basis of insulin aggregation is relevant for modeling the amyloidogenesis process, which is involved in many pathologies, as well as for improving delivery systems, used for diabetes treatments. Insulin aggregation displays a wide variety of morphologies, from small oligomeric filaments to huge floccules, and therefore different specific processes are likely to be intertwined in the overall aggregation. In the present work, we studied the aggregation kinetics of human insulin at low pH and different temperatures and concentrations. The structure and the morphogenesis of aggregates on a wide range…
The kinetic behavior of insulin fibrillation is determined by heterogeneous nucleation pathways
2005
When subjected to acidic conditions and high temperature, insulin is known to produce fibrils that display the common properties of disease amyloids. Thus, clarifying the mechanisms of insulin fibrillation can help the general understanding of amyloidal aggregation. Insulin fibrillation exhibits a very sharp time dependence, with a pronounced lag phase and subsequent explosive growth of amyloidal aggregates. Here we show that the initial stages of this process can be well described by exponential growth of the fibrillated proteins. This indicates that the process is mainly controlled by a secondary nucleation pathway.
Secondary nucleation and accessible surface in insulin amyloid fibril formation.
2008
At low pH insulin is highly prone to self-assembly into amyloid fibrils. The process has been proposed to be affected by the existence of secondary nucleation pathways, in which already formed fibrils are able to catalyze the formation of new fibrils. In this work, we studied the fibrillation process of human insulin in a wide range of protein concentrations. Thioflavin T fluorescence was used for its ability to selectively detect amyloid fibrils, by mechanisms that involve the interaction between the dye and the accessible surface of the fibrils. Our results show that the rate of fibrillation and the Thioflavin T fluorescence intensity saturate at high protein concentration and that, surpr…
Polysorbate 80 controls Morphology, structure and stability of human insulin Amyloid-Like spherulites
2022
AbstractAmyloid protein aggregates are not only associated with neurodegenerative diseases and may also occur as unwanted by-products in protein-based therapeutics. Surfactants are often employed to stabilize protein formulations and reduce the risk of aggregation. However, surfactants alter protein-protein interactions and may thus modulate the physicochemical characteristics of any aggregates formed. Human insulin aggregation was induced at low pH in the presence of varying concentrations of the surfactant polysorbate 80. Various spectroscopic and imaging methods were used to study the aggregation kinetics, as well as structure and morphology of the formed aggregates. Molecular dynamics s…
Metabolic impact of adult-onset, isolated, growth hormone deficiency (AOiGHD) due to destruction of pituitary somatotropes.
2011
Growth hormone (GH) inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD) was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre) with inducible diphtheria toxin receptor mice (iDTR) and treating adult Cre(+/-), iDTR(+/-) offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre(-/-), iDTR(+/-) mice were used as GH-intact controls. AOiGHD im…
Der Einfluß von extremen Ausdauerbelastungen auf den Eiweißstoffwechsel des Menschen mit besonderer Berücksichtigung des Immunsystems
1985
In summer 1981, six long-distance runners covered a 1100-km-course across the Federal Republic of Germany within 20 days. Four of them were on a more or less ovo-lacto-vegetable and two a vegetarian diet. In spite of a high absolute but indeed low relative protein supply, a continuous decrease of the total protein content could be noticed in the serum. The alterations of the protein fractions corresponded to those of an acute-phase reaction. The Immunoglobulin-G and the Immunoglobulin-A content decreased continuously. The cortisol level was always above the norm, the insulin level always below. The glucagon level increased continuously in the course of the day. The urea-N-level moved around…
Mullarian-inhibiting substance reflects ovarian findings in women with polycystic ovary syndrome better than does inhibin-B
2005
Objective: To investigate Müllerian-inhibiting substance (MIS) levels in women with polycystic ovary syndrome (PCOS), as well as relationships to ovarian morphology, levels of inhibin B, and other reproductive hormones. Design: Prospective clinical study. Setting: Academic endocrinology centers in Palermo, Italy and New York. Patient(s): Forty-six women with PCOS, recruited on the basis of the classic criteria of chronic anovulation and hyperandrogenism, and 25 age-matched ovulatory controls. Intervention(s): Fasting blood was obtained in all subjects in the early follicular phase (days 5–6) after spontaneous or induced menses (in PCOS), and transvaginal ultrasounds were performed. Main Out…
Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with coronary artery disease.
2005
Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the classical nonlipid risk factors and/or high plasma lipid levels and evaluated the plasma concentration of TRL subspecies in comparison with healthy controls. Patients with CAD and controls had total cholesterol and TG levels within the normal range (despite slightly, even…
Relationship Between the Apolipoprotein E Genotype and LDL Particle Size in Patients With Obstructive Sleep Apnea.
2016
Obstructive sleep apnea (OSA) is associated with dyslipidemia and increased cardiovascular risk. We assessed the effects of apolipoprotein E ( APOE) genotype on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size and lipid subclasses (separated by gradient gel electrophoresis) in patients with OSA. Stable patients (n = 181) prospectively recruited underwent full polysomnography. Both LDL particle size and LDL I proportion were reduced from ∊3∊3 homozygotes to ∊2 carriers and to ∊4 carriers (analysis of variance: P = .024; P = .040, respectively); carriers of the ∊4 allele of the APOE genotype had significantly lower LDL particle size and LDL I proportion compared…