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101.
S. Giannini B. Cresci C. Manuelli Y. Fujita-Yamaguchi P. Romagnani S. Mohan C.M. Rotella 《Metabolism: clinical and experimental》1997,46(12):1367-1379
Retinopathy is the most frequent microangiopathic complication in diabetes. Many circulating hormones and locally produced mitogenic factors have been involved. Bovine retinal endothelial cells (BRECs) were cultured to investigate if insulin, insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and a chronic high-glucose condition could control endothelial cell growth. Specific IGF-I receptors with two binding sites with high (Kd 0.03 nmol/L) and low (Kd 1.3 nmol/L) affinity were found when analyzing families of displacement curves between IGF-I versus IGF-I and IGF-I versus insulin. However, IGFs failed to be mitogenic factors in these cells. This could be explained by an inhibitory effect due to the presence of specific IGFBPs with a molecular weight between 24 and 43 kd. Using Western blot and immunoblot analysis, Northern blot study, and specific radioimmunoassay (RIA), these IGFBPs have been identified as IGFBP-3, -2, -5, and -4. Insulin, which does not bind to IGFBPs, was a potent mitogenic factor in these cells at a high concentration (10 nmol/L), suggesting a cross-reaction to IGF-I receptor. These IGFBPs, except the 24-kd form (IGFBP-4), were modulated by both IGF-I and IGF-II, with a maximum effect at 100 and 10 nmol/L, respectively. This regulation on IGFBPs was IGF-I receptor—independent. In fact, (1) IGFBP mRNA levels were not modified after stimulation with 100 nmol/L IGF-I, (2) 100 nmol/L IGF plus an equimolar concentration of αIR3 did not affect IGFBP production, (3) Des(1–3)IGF-I had no effect on IGFBP modulation, whereas at 10 nmol/L it enhanced BREC thymidine cell incorporation, and (4) 100 nmol/L insulin, which at this concentration can cross-react with the IGF-I receptor, did not modify the IGFBP pattern. Chronic exposure (4 weeks) of BRECs to 25 mmol/L glucose had no effect on cell growth. However, after 3 weeks, we observed a decreased IGFBP detection, and addition of 100 nmol/L IGF-I did not change IGFBP levels and did not modify cell growth. Conversely, BRECs grown in regular medium for 4 weeks showed increased IGFBP production. In conclusion, we showed that conditions mimicking hyperinsulinemia, rather than high levels of IGFs, could regulate BREC growth and that the IGF-I analog, Des(1–3), even with reduced affinity for IGFBPs but in part capable of binding to IGFBP-3, significantly stimulated BRECs growth only at 10 nmol/L. IGF actions are modulated by locally produced endothelial IGFBPs, and in turn, these endothelial IGFBPs are regulated, via an IGF-I receptor—independent mechanism, by the presence of IGFs. The autoregulatory IGF system together with the direct glucose modulation of IGFBPs could contribute in diabetic subjects to the retinal endothelial cell growth and metabolism through local changes in IGF bioavailability. 相似文献
102.
P Gorwood J Adès L Bellodi E Cellini D A Collier D Di Bella M Di Bernardo X Estivill F Fernandez-Aranda M Gratacos J Hebebrand A Hinney X Hu A Karwautz A Kipman M C Mouren-Siméoni B Nacmias M Ribasés H Remschmidt V Ricca C M Rotella S Sorbi J Treasure 《Molecular psychiatry》2002,7(1):90-94
Several case-control association studies have raised the possibility that the A allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar chi(2) = 0.29, df = 1, P = 0.59). Also, the haplotype-based haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre (chi(2) < 2.15, df = 1, P > 0.14) and in the total sample (chi(2) = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples (chi(2) = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT(2A) gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size). 相似文献
103.
AimsGlucagon-like peptide-1 (GLP-1), a gastrointestinal hormone mainly produced in the post-prandial state, reduces blood glucose through the stimulation of insulin secretion and the inhibition of glucagon release. Long-acting GLP-1 receptor agonists, and dipeptidyl-peptidase-4 (DPP-4) inhibitors which increase GLP-1 levels, are used as hypoglycemic treatments in type 2 diabetes. This paper aims at reviewing the potential benefit of those treatments in the prevention of cardiovascular risk in type 2 diabetic patients.Data synthesisExperimental studies have shown that GLP-1 has several potentially beneficial actions on cardiovascular risk. Some of those, such as protection from myocardial ischemic damage and improvement of cardiac function, have also been demonstrated in humans. However, the equivalence of GLP-1 agonists and DPP-4 inhibitors with GLP-1, with respect to cardiovascular risk profile, cannot be assumed or taken for granted. Drugs of those two classes have been shown to effectively reduce glycated hemoglobin and to have a specific effect on post-prandial glucose; furthermore, they seem to reduce blood pressure and to have some favorable effects on lipid profiles. Additionally, GLP-1 agonists induce weight loss in diabetic patients.ConclusionThe profile of action of GLP-1 receptor agonists and DPP-4 inhibitors suggests the possibility of an actual reduction in cardiovascular risk, which needs to be confirmed by large long-term clinical trials. 相似文献
104.
Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects 总被引:3,自引:0,他引:3
Mannucci E Ognibene A Cremasco F Bardini G Mencucci A Pierazzuoli E Ciani S Messeri G Rotella CM 《Diabetes care》2001,24(3):489-494
OBJECTIVE: To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels. RESEARCH DESIGN AND METHODS: A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7-36)amide/(7-37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7-36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied. RESULTS: Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7-36)amide/(7-37) at 30 and 60 min after the oral glucose load (63.8 +/- 29.0 vs. 50.3 +/- 15.6 pmol/l and 75.8 +/- 35.4 vs. 46.9 +/- 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels were observed in the control group. In pooled human plasma, metformin (0.1-0.5 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees C; similar results were obtained in a buffer solution containing DPP-IV. CONCLUSIONS: Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation. 相似文献
105.
Monami M Colombi C Balzi D Dicembrini I Giannini S Melani C Vitale V Romano D Barchielli A Marchionni N Rotella CM Mannucci E 《Diabetes care》2011,34(1):129-131
OBJECTIVE
Metformin is associated with reduced cancer-related morbidity and mortality. The aim of this study was to assess the effect of metformin on cancer incidence in a consecutive series of insulin-treated patients.RESEARCH DESIGN AND METHODS
A nested case-control study was performed in a cohort of 1,340 patients by sampling, for each case subject, age-, sex-, and BMI-matched control subjects from the same cohort.RESULTS
During a median follow-up of 75.9 months, 112 case patients who developed incident cancer and were compared with 370 control subjects. A significantly lower proportion of case subjects were exposed to metformin and sulfonylureas. After adjustment for comorbidity, glargine, and total insulin doses, exposure to metformin, but not to sulfonylureas, was associated with reduced incidence of cancer (odds ratio 0.46 [95% CI 0.25–0.85], P = 0.014 and 0.75 [0.39–1.45], P = 0.40, respectively).CONCLUSIONS
The reduction of cancer risk could be a further relevant reason for maintaining use of metformin in insulin-treated patients.Several studies have shown that metformin is associated with reduced cancer-related morbidity and mortality (1–4), due to improvement in insulin sensitivity (5) or to the activation of AMP-activated protein kinase (6). In insulin-treated patients, the reduction in insulin doses determined by metformin (7) could theoretically produce a decrease in cancer incidence. 相似文献106.
Lack of adequate mesiodistal space and/or incorrect implant placement may not provide adequate space for the fabrication, insertion, and maintenance of implant crowns. This report describes the clinical presentation of a patient requiring restoration of a dental implant without adequate interproximal space due to mesial drift of the adjacent tooth. Orthodontic tooth movement was achieved with an osseointegrated dental implant and orthodontic elastics. 相似文献
107.
108.
109.
Lisa Lazzeretti Francesco Rotella Laura Pala Carlo Maria Rotella 《World Journal of Psychiatry》2015,5(1):56-67
Obesity is a multifactorial disease and the prominent factors playing a role in its pathogenesis are biological, environmental and psychological. There is a growing interest in understanding psychological functioning of obese subjects and the influence of psychological factors on treatment outcome. The aim of the present narrative review is to critically analyze the current literature, in order to point out the most common psychological constructs studied in obesity and to give an overview of the main existing tools investigating psychological features which have been considered significant for the prediction of success in weight loss and maintenance programs in obese patients. In this framework, the most common psychological constructs studied are: self-motivation, self-efficacy, locus of control, health related quality of life, self-esteem, self-control, concerns about body image, outcome expectations, and personality traits. These features have been explored through a wide variety of psychometric instruments. However, as an overall, studies evaluating the association between psychological features and treatment outcome failed to give consistent results. A possible explanation may consist on the fact that many tools widely used to explore psychological features were not specifically designed for obese patients and none of them was comprehensive of all possible psychological features involved. The identification of well-defined sub-groups of patients and the validation of more reliable and comprehensive tools, specifically designed for obese subjects, should be forecasted in order to reach a better knowledge of psychological functioning of obese individuals and to improve the outcome of weight loss programs. 相似文献
110.
Egidio Imbalzano Marco Vatrano Sebastiano Quartuccio Roberto Ceravolo Vincenzo Antonio Ciconte Paola Rotella Renato Pardeo Giovanni Trapani Pasquale De Fazio Cristina Segura‐Garcia Rossella Costantino Antonino Saitta Giuseppe Mandraffino 《Clinical cardiology》2018,41(3):321-325