oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2019 ( 1 )

2018 ( 4 )

2016 ( 3 )

2015 ( 41 )

Custom range...

Search Results: 1 - 10 of 552 matches for " Edoardo Mannucci "
All listed articles are free for downloading (OA Articles)
Page 1 /552
Display every page Item
Insulin Therapy and Cancer in Type 2 Diabetes
Edoardo Mannucci
ISRN Endocrinology , 2012, DOI: 10.5402/2012/240634
Abstract: Despite the availability of many other agents, insulin is widely used as a treatment for type 2 diabetes. In vitro, insulin stimulates the growth of cancer cells, through the interaction with insulin-like growth factor-1 (IGF-1) receptors and its own receptors. In observational surveys on type 2 diabetes, insulin therapy is associated with an increased incidence of several forms of cancer, although it is difficult to discriminate the effect of confounders from that of insulin itself. Randomized trials do not confirm the increased risk associated with insulin therapy, although they do not allow to rule out some negative effects on specific forms of cancer, at least at higher doses. Among insulin analogues, glargine has a higher affinity for the IGF-1 receptor and a greater mitogenic potency in vitro than human insulin, but it is extensively metabolized in vitro to products with low IGF-1 receptor affinity. Overall, epidemiological studies suggest a possible increase of risk with glargine, with respect to human insulin, only at high doses and for some forms of cancer (i.e., breast). Data from clinical trials do not confirm, but are still insufficient to totally exclude, such increased risk. However, beneficial effects of insulin outweigh potential cancer risks. 1. Introduction Type 2 diabetes is associated with an increased incidence of malignancies and cancer-related mortality [1]. In particular, the risk of liver [1–3] and pancreas [1, 4] cancer is markedly increased in patients with type 2 diabetes, whereas other cancer types (e.g., bowel [5], stomach [6], leukemia/lymphoma [7], and breast [8]) are only moderately augmented, and other forms of malignancies (e.g., lung cancer [1]) seem to be unaffected by diabetes. As an exception, individuals with type 2 diabetes seem to be protected from prostate cancer [9]. The mechanisms underlying the association of type 2 diabetes with cancer are complex and not yet fully understood. The elevated incidence of hepatocellular carcinoma in patients with diabetes could be related to the common association of diabetes with nonalcoholic fatty liver disease, and with viral hepatic disease, which are both risk factors for hepatic cancer [3]. It has also been suggested that chronic exposure to hyperglycemia and hyperinsulinemia, in patients with type 2 diabetes, could contribute to the proliferation of hepatic stem cells, at higher risk for malignant transformation [10]. As for pancreatic cancer, undiagnosed neoplastic proliferation, leading to impaired insulin secretion, could facilitate the development of hyperglycemia;
Incretins and the specific mechanism of action of liraglutide, the first applicable human glucagon-like peptide 1 analog in the treatment of type 2 diabetes
Edoardo Mannucci, Caterina Lamanna
Journal of Receptor, Ligand and Channel Research , 2010, DOI: http://dx.doi.org/10.2147/JRLCR.S6345
Abstract: cretins and the specific mechanism of action of liraglutide, the first applicable human glucagon-like peptide 1 analog in the treatment of type 2 diabetes Review (3412) Total Article Views Authors: Edoardo Mannucci, Caterina Lamanna Published Date September 2010 Volume 2010:3 Pages 105 - 112 DOI: http://dx.doi.org/10.2147/JRLCR.S6345 Edoardo Mannucci, Caterina Lamanna Diabetes Agency, Careggi Teaching Hospital, Florence, Italy Abstract: Liraglutide is a once-daily glucagon-like peptide 1 (GLP-1) receptor agonist, approved for use as a treatment of type 2 diabetes. Like other drugs of the same class, liraglutide stimulates insulin secretion in a glucose-dependent fashion, has the potential of preventing β-cell mass decline, and inhibits food intake. In addition, experimental studies suggest that the GLP-1 receptor agonists could protect myocardium from ischemic injury, enhancing cardiac function. In clinical trials, liraglutide (in monotherapy or as add-on to 1 or 2 oral drugs) is as effective as, or more effective than, other agents (sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, insulin, and exenatide) in reducing hemoglobin A1c; induces weight loss; and has a blood pressure-lowering effect. The possible beneficial cardiovascular effects need to be confirmed by specifically designed long-term studies.
Incretins and the specific mechanism of action of liraglutide, the first applicable human glucagon-like peptide 1 analog in the treatment of type 2 diabetes
Edoardo Mannucci,Caterina Lamanna
Journal of Receptor, Ligand and Channel Research , 2010,
Abstract: Edoardo Mannucci, Caterina LamannaDiabetes Agency, Careggi Teaching Hospital, Florence, ItalyAbstract: Liraglutide is a once-daily glucagon-like peptide 1 (GLP-1) receptor agonist, approved for use as a treatment of type 2 diabetes. Like other drugs of the same class, liraglutide stimulates insulin secretion in a glucose-dependent fashion, has the potential of preventing β-cell mass decline, and inhibits food intake. In addition, experimental studies suggest that the GLP-1 receptor agonists could protect myocardium from ischemic injury, enhancing cardiac function. In clinical trials, liraglutide (in monotherapy or as add-on to 1 or 2 oral drugs) is as effective as, or more effective than, other agents (sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, insulin, and exenatide) in reducing hemoglobin A1c; induces weight loss; and has a blood pressure-lowering effect. The possible beneficial cardiovascular effects need to be confirmed by specifically designed long-term studies.Keywords: liraglutide, type 2 diabetes, GLP-1 receptor agonist
Bone: Incretin Hormones Perceiver or Receiver?
Ilaria Dicembrini,Edoardo Mannucci,Carlo Maria Rotella
Experimental Diabetes Research , 2012, DOI: 10.1155/2012/519784
Abstract: Novel incretin-based drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), have been last introduced in the pharmacological treatment of type 2 diabetes. In the last few years, the interest on the relationship of gut hormones with bone metabolism in diabetes has been increasing. The aim of present paper is to examine in vitro and in vivo evidence on the connections between incretin hormones and bone metabolism. We also discuss results of clinical trials and metaanalysis, explore the effects of incretin drugs in vitro on osteogenic cells and osteoclasts, and speculate on the possibility of different effects of GLP-1 RA and DPP-4i on the risk of bone fractures risk in humans. Although existing preliminary evidence suggests a protective effect on the bone, at least for DPP-4i, further controlled, long-term studies with measurement of bone markers, bone density, and clinical fractures rates are needed to substantiate and confirm those findings.
Bone: Incretin Hormones Perceiver or Receiver?
Ilaria Dicembrini,Edoardo Mannucci,Carlo Maria Rotella
Journal of Diabetes Research , 2012, DOI: 10.1155/2012/519784
Abstract: Novel incretin-based drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), have been last introduced in the pharmacological treatment of type 2 diabetes. In the last few years, the interest on the relationship of gut hormones with bone metabolism in diabetes has been increasing. The aim of present paper is to examine in vitro and in vivo evidence on the connections between incretin hormones and bone metabolism. We also discuss results of clinical trials and metaanalysis, explore the effects of incretin drugs in vitro on osteogenic cells and osteoclasts, and speculate on the possibility of different effects of GLP-1 RA and DPP-4i on the risk of bone fractures risk in humans. Although existing preliminary evidence suggests a protective effect on the bone, at least for DPP-4i, further controlled, long-term studies with measurement of bone markers, bone density, and clinical fractures rates are needed to substantiate and confirm those findings. 1. Introduction Glucose, protein, and fat and mixed meal ingestion is associated with a significant reduction in markers of bone resorption, detectable by twenty minutes after feeding [1]. Bone formation is also influenced, but it seems to be less responsive to nutrients than resorption [2]. Biochemical assessment of bone turnover demonstrates that food intake is the major cause of the reduced bone turnover during daytime, which is followed by a nocturnal increase [3]. In addition, the observation that parenteral feeding is related to bone mass reduction [4] suggests a functional link between gut and bone metabolism through hormones responding to nutrients absorption, such as, incretins. The concept of incretins has been introduced to define gastrointestinal hormones released after meal ingestion, which modulate glucose homeostasis, mainly through both glucose-induced enhancement of insulin secretion and inhibition of glucagon release, such as glucagon-like peptide-1 (GLP-1). Beneficial extraglycemic actions on body weight, blood pressure, dyslipidemia, cardiac and endothelial function are further reported. Novel drugs based on the incretin system, such as, glucagon-like peptide-1 receptor agonists (GLP-1 RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i), have been approved for the therapy of type 2 diabetes [5]. In the last few years, the interest on the relationship of gut hormones with bone formation and turnover in diabetes has been increasing, with preliminary data suggesting the possibility of positive effects of GLP-1 RA and DPP-4i on bone health.
Effects of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight: A Meta-Analysis
Matteo Monami,Ilaria Dicembrini,Niccolò Marchionni,Carlo M. Rotella,Edoardo Mannucci
Experimental Diabetes Research , 2012, DOI: 10.1155/2012/672658
Abstract: Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for “exenatide,” “liraglutide,” “albiglutide,” “semaglutide,” and “lixisenatide” was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of −1.0 [−1.3; −0.6] kg/m2. Considering the average BMI at baseline (32.4 kg/m2) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction.
Losartan counteracts the hyper-reactivity to angiotensin II and ROCK1 over-activation in aortas isolated from streptozotocin-injected diabetic rats
Paola Failli, Chiara Alfarano, Sergio Franchi-Micheli, Edoardo Mannucci, Elisabetta Cerbai, Alessandro Mugelli, Laura Raimondi
Cardiovascular Diabetology , 2009, DOI: 10.1186/1475-2840-8-32
Abstract: We now aimed to investigate the effect of treating diabetic STZ-rats with losartan on diabetes vascular response to vasoconstrictors.Male Wistar rats were randomly divided in four groups, two of them were assigned to receive losartan in the drinking water (20 mg/kg/day) until the experiment ending (3 weeks afterward). After 1 week, two groups, one of which receiving losartan, were injected in the tail vein with citrate buffer (normoglycemic, N and normoglycemic, losartan-treated, NL). The remaining received a single injection of streptozotocin (50 mg/kg in citrate i.v.) thus becoming diabetic (D) and diabetic losartan-treated (DL). Plasma glycaemia and blood pressure were measured in all animals before the sacrifice (15 days after diabetes induction).In aortic strips isolated from N, NL, D and DL rats we evaluated i) the isometric concentration-dependent contractile response to phenylephrine (Phe) and to AT-II; ii) the RhoA-kinase (ROCK1) activity and expression by enzyme-immunoassay and Western blot respectively.The concentration-dependent contractile effect of Phe was similar in aortas from all groups, whereas at all concentrations tested, AT-II contraction efficacy was 2 and half and 1 and half times higher in D and DL respectively in comparison with N and NL. AT-II contracture was similarly reduced in all groups by AT-II receptor antagonists, irbesartan or irbesartan plus PD123319. HA-1077 (10 μM), an inhibitor of ROCK1 activity, reduced AT-II efficacy (Δmg/mg tissue w.w.) by -3.5 ± 1.0, -4.6 ± 1.9, -22.1 ± 2.2 and -11.4 ± 1.3 in N, NL, D and DL respectively). ROCK1 activity and expression were higher in D than in N/NL and DL aortas.Aortas isolated from STZ-rats present hyper-contracture to AT-II mainly dependent on the up-regulation of ROCK1 expression/activity. In vivo losartan treatment partially corrects AT-II hyper-contracture, limiting the increase in ROCK1 expression/activity. These data offer a new molecular mechanism supporting the rationale for using l
Effects of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight: A Meta-Analysis
Matteo Monami,Ilaria Dicembrini,Niccolò Marchionni,Carlo M. Rotella,Edoardo Mannucci
Journal of Diabetes Research , 2012, DOI: 10.1155/2012/672658
Abstract: Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for “exenatide,” “liraglutide,” “albiglutide,” “semaglutide,” and “lixisenatide” was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of ?1.0 [?1.3; ?0.6]?kg/m2. Considering the average BMI at baseline (32.4?kg/m2) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction. 1. Introduction Most drugs developed for the therapy of obesity have failed to show a sufficient efficacy and safety for long-term treatment. In particular, agents which stimulate energy expenditure (e.g., thyroid hormones, sympathoadrenergic drugs, or sibutramine) do not have an adequate cardiovascular safety, whereas centrally acting anorexants either are ineffective in the long term (e.g., serotonin reuptake inhibitors) or show neuropsychiatric adverse effects (e.g., amphetamine derivatives or cannabinoid receptor antagonists) [1]. As a result, orlistat, which inhibits lipid absorption, is the only available drug for obesity in many countries. Even for drugs which do not show relevant problems of long-term safety, such as orlistat, the unsatisfactory tolerability profile limits clinical use. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, produced mainly in the postprandial phase, which stimulates insulin secretion and inhibits glucagon release in a dose-dependent fashion [2]. Due to this properties, the hormone reduces hyperglycemia without inducing hypoglycemia in patients with type 2 diabetes [3]. The rapid inactivation of GLP-1 in vivo and the consequent short half-life (a few minutes after subcutaneous administration) prevents its therapeutic use. Long-acting GLP-1 receptor agonists, which can be administered
Glucagon-Like Peptide-1 and Diabetes 2012
Matteo Monami,Giovanni Di Pasquale,Anna Rowzee,Carlo Maria Rotella,Edoardo Mannucci
Journal of Diabetes Research , 2012, DOI: 10.1155/2012/768760
Abstract:
Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Events: A Meta-Analysis of Randomized Clinical Trials
Matteo Monami,Francesco Cremasco,Caterina Lamanna,Claudia Colombi,Carla Maria Desideri,Iacopo Iacomelli,Niccolò Marchionni,Edoardo Mannucci
Experimental Diabetes Research , 2011, DOI: 10.1155/2011/215764
Abstract: Objective. Data from randomized clinical trials with metabolic outcomes can be used to address concerns about potential issues of cardiovascular safety for newer drugs for type 2 diabetes. This meta-analysis was designed to assess cardiovascular safety of GLP-1 receptor agonists. Design and Methods. MEDLINE, Embase, and Cochrane databases were searched for randomized trials of GLP-1 receptor agonists (versus placebo or other comparators) with a duration ≥12 weeks, performed in type 2 diabetic patients. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for major cardiovascular events (MACE), on an intention-to-treat basis, excluding trials with zero events. Results. Out of 36 trials, 20 reported at least one MACE. The MH-OR for all GLP-1 receptor agonists was 0.74 (0.50–1.08), =.12 (0.85 (0.50–1.45), =.55, and 0.69 (0.40–1.22), =.20, for exenatide and liraglutide, resp.). Corresponding figures for placebo-controlled and active comparator studies were 0.46 (0.25–0.83), =.009, and 1.05 (0.63–1.76), =.84, respectively. Conclusions. To date, results of randomized trials do not suggest any detrimental effect of GLP-1 receptor agonists on cardiovascular events. Specifically designed longer-term trials are needed to verify the possibility of a beneficial effect.
Page 1 /552
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.