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1.
Am J Transplant ; 18(4): 945-951, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28941330

RESUMO

In allogenic islet transplantation (IT), high purity of islet preparations and low contamination by nonislet cells are generally favored. The aim of the present study was to analyze the relation between the purity of transplanted preparations and graft function during 5 years post-IT. Twenty-four patients with type 1 diabetes, followed for 5 years after IT, were enrolled. Metabolic parameters and daily insulin requirements were compared between patients who received islet preparations with a mean purity <50% (LOW purity) or ≥50% (HIGH purity). We also analyzed blood levels of carbohydrate antigen 19-9 (CA 19-9)-a biomarker of pancreatic ductal cells-and glucagon, before and after IT. At 5 years, mean hemoglobin A1c (HbA1c levels) (P = .01) and daily insulin requirements (P = .03) were lower in the LOW purity group. Insulin independence was more frequent in the LOW purity group (P < .05). CA19-9 and glucagon levels increased post-IT (P < .0001) and were inversely correlated with the degree of purity. Overall, our results suggest that nonislet cells have a beneficial effect on long-term islet graft function, possibly through ductal-to-endocrine cell differentiation. ClinicalTrial.gov NCT00446264 and NCT01123187.


Assuntos
Glicemia/metabolismo , Separação Celular/métodos , Diabetes Mellitus Tipo 1/terapia , Hemoglobinas Glicadas/metabolismo , Sobrevivência de Enxerto , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/citologia , Adulto , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Seguimentos , Humanos , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
2.
Int J Obes (Lond) ; 41(4): 664-668, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28093571

RESUMO

Roux-en-Y gastric bypass (RYGB) surgery is widely used in the management of morbid obesity. RYGB improves metabolism independently of weight loss by still unknown mechanisms. Bile acids (BAs) are good candidates to explain this benefit, since they regulate metabolic homeostasis and their systemic concentrations increase upon RYGB. Here we analyzed the mechanisms underlying the increase in systemic BA concentrations after RYGB and the role of the liver therein. To this aim, we used the Göttingen-like minipig, a human-size mammalian model, which allows continuous sampling and simultaneous analysis of pre-hepatic portal and systemic venous blood. BA concentrations and pool composition were measured in portal blood, containing intestinal reabsorbed BAs and compared to systemic blood during a standardized meal test before and after RYGB. Systemic total BA concentrations increased after RYGB, due to an increase in conjugated BAs. Interestingly, the ratio of portal:systemic conjugated BAs decreased after RYGB, indicating a role for the liver in systemic BA concentrations changes. In line, hepatic expression of BA transporter genes decreased after RYGB. Our results show that the increase in systemic BAs after surgery is due to decreased selective hepatic recapture. Thus, alterations in hepatic function contribute to the increase in systemic BAs after RYGB.


Assuntos
Ácidos e Sais Biliares/metabolismo , Derivação Gástrica , Fígado/metabolismo , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Porco Miniatura/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Suínos , Redução de Peso/fisiologia
3.
Int J Obes (Lond) ; 40(8): 1260-7, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27089995

RESUMO

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is the most widely used bariatric surgery procedure, which induces profound metabolic and physiological effects, such as substantial improvements in obesity, type 2 diabetes and their comorbidities. Increasing evidence identifies bile acids (BAs) as signaling molecules that contribute to the metabolic improvement after RYGBP. However, how and to what extent BAs mediate the metabolic effects of RYGBP still remains unclear and requires mechanism of action studies using preclinical models. In this study, we compared plasma BA profiles before and after RYGBP in two animal models, rats and pigs, with humans to evaluate their translational potential. METHODS: Plasma BAs were profiled in rats, pigs and humans by liquid chromatography coupled with tandem mass spectrometry before and after RYGBP. RESULTS: RYGBP increased baseline plasma total BA concentrations in humans and in the two animal models to a similar extent (∼3-fold increase), despite differences in presurgery BA levels and profiles between the models. However, qualitatively, RYGBP differently affected individual plasma BA species, with similar increases in some free species (cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)), different increases in glyco-conjugated species depending on the model and globally no increase in tauro-conjugated species whatever the model. CONCLUSIONS: The tested animal models share similar quantitative RYGBP-induced increases in peripheral blood BAs as humans, which render them useful for mechanistic studies. However, they also present qualitative differences in BA profiles, which may result in different signaling responses. Such differences need to be taken into account when translating results to humans.


Assuntos
Ácidos e Sais Biliares/sangue , Derivação Gástrica , Obesidade/sangue , Obesidade/cirurgia , Adulto , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Ratos , Transdução de Sinais , Suínos , Porco Miniatura , Resultado do Tratamento , Redução de Peso
4.
Eur Surg Res ; 52(1-2): 41-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24557358

RESUMO

BACKGROUND: Gastric bypass in obese patients induces a dramatic increase of postprandial insulin and glucagon-like peptide-1 (GLP-1) secretion, independently of weight loss. We explored postprandial insulin and GLP-1 secretion in nonobese minipigs before and after RYGB. METHODS: Lean adult Göttingen minipigs (n = 7) were submitted to an open gastric bypass surgery mimicking the clinical procedure in humans (30-cm(3) gastric pouch/150-cm alimentary limb/70-cm biliary limb). All animals were evaluated at baseline and then 10 and 30 days after surgery. At each time point, serum glucose, insulin, GLP-1 and D-xylose levels were measured 3 h after a standardized mixed meal. RESULTS: Weight remained stable during follow-up. Insulin and GLP-1 responses to the test meal were dramatically and similarly increased at 10 days and 1 month after RYGB. Maximal postprandial insulin and GLP-1 levels were 16.3 ± 1.7 mIU/l and 71.7 ± 16.5 pmol/l at baseline, 111.5 ± 38.9 mIU/l and 320.8 ± 84.0 pmol/l at 10 days and 96.6 ± 10.4 mIU/l and 297.3 ± 79.1 pmol/l at 1 month, respectively. D-Xylose absorption remained unchanged before and after surgery. CONCLUSIONS: RYGB induced a dramatic increase of postprandial insulin and GLP-1 secretion in nonobese minipigs. This preclinical model could help to understand the underlying metabolic effects of RYGB, focusing on the role of postsurgical anatomical rearrangement, especially duodenojejunal exclusion and ileal brake. This study supports the use of RYGB in diabetic nonobese patients in absence of obesity.


Assuntos
Derivação Gástrica , Peptídeo 1 Semelhante ao Glucagon/sangue , Insulina/sangue , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Humanos , Modelos Anatômicos , Modelos Animais , Obesidade/sangue , Obesidade/cirurgia , Período Pós-Prandial/fisiologia , Suínos , Porco Miniatura , Xilose/sangue
5.
Diabetologia ; 56(2): 350-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23192693

RESUMO

AIMS/HYPOTHESIS: In this study, we used an immunodeficient mouse model to explore, in vivo, the longitudinal adaptation of human islets to an obesogenic environment. METHODS: Non-diabetic Rag2 (-/-) mice (n = 61) were transplanted with human islets (400 islet equivalents [IEQ]) from six pancreases: four non-diabetic and two with overt metabolic dysfunction (older, high HbA(lc) or history of diabetes). Animals were fed for 12 weeks with a control or high-fat diet (HFD), and followed for weight, serum triacylglycerol, fasting blood glucose and human C-peptide. After the mice were killed, human grafts and the endogenous pancreas were analysed for endocrine volume, distribution of beta and alpha cells, and proliferation. RESULTS: Transplanted mice on an HFD gained significantly more weight (p < 0.001) and had higher fasting glycaemia (2-12 weeks; p = 0.0002) and consistently higher fasting human C-peptide levels (2-12 weeks; p = 0.04) compared with those on the control diet. Histology demonstrated doubling of human islet graft volume at 12 weeks in animals on the HFD and increased beta cell volume (p < 0.001), but no change in alpha cell volume. Human islet function (hyperbolic product HOMA2%BS) at 12 weeks was four times lower in HFD animals (p < 0.001 vs controls) because of insufficient beta cell adaptation to decreased (70%) sensitivity (HOMA%S). Human islets obtained from donors with metabolic dysfunction failed to adapt to the HFD. CONCLUSIONS/INTERPRETATION: This longitudinal study provides direct evidence that human islets adapt both endocrine and beta cell mass, function and gene expression to obesity in vivo. The present model will facilitate the identification of mechanisms by which human islets adapt to obesity in vivo and the cell type(s) responsible, and factors predisposing human beta cells to decompensation.


Assuntos
Ilhotas Pancreáticas/fisiologia , Animais , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Dieta Hiperlipídica/efeitos adversos , Humanos , Imuno-Histoquímica , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Transplante das Ilhotas Pancreáticas , Masculino , Camundongos , Obesidade/metabolismo , Reação em Cadeia da Polimerase
6.
Am J Transplant ; 13(4): 891-898, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23496914

RESUMO

The liver may not be an optimal site for islet transplantation due to obstacles by an instant blood-mediated inflammatory response (IBMIR), and low revascularization of transplanted islets. Therefore, intramuscular islet transplantation (IMIT) offers an attractive alternative, based on its simplicity, enabling easier access for noninvasive graft imaging and cell explantation. In this study, we explored the outcome of autologous IMIT in the minipig (n = 30). Using the intramuscular injection technique, we demonstrated by direct histological evidence the rapid revascularization of islets autotransplanted into the gracilius muscle. Islet survival assessment was performed using immunohistochemistry staining for insulin and glucagon up to a period of 6 months. Furthermore, we showed the crucial role of minimizing mechanical trauma to the myofibers and limiting exocrine contamination. Intramuscular islet graft function after transplantation was confirmed by documenting the acute insulin response to intravenous glucose in 5/11 pancreatectomized animals. Graft function after IMIT remained however significantly lower than the function measured in 12 out of 18 minipigs who received a similar islet volume in the liver through intraportal infusion. Collectively, these results demonstrated in a clinically relevant preclinical model, suggest IMIT as a promising alternative to intraportal infusion for the transplantation of ß cells in certain medical situations.


Assuntos
Sobrevivência de Enxerto , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/citologia , Músculos/citologia , Transplante Heterotópico , Animais , Sobrevivência Celular , Fibrose , Glucagon/metabolismo , Glucose/metabolismo , Hipóxia , Injeções Intramusculares , Insulina/metabolismo , Músculos/irrigação sanguínea , Neovascularização Fisiológica , Pâncreas/cirurgia , Suínos , Porco Miniatura , Transplante Autólogo
7.
Langenbecks Arch Surg ; 398(5): 729-33, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23250652

RESUMO

PURPOSE: The aim of this study was to assess the safety and efficacy of adrenalectomy on patients with pheochromocytoma diagnosed at the time of an acute heart failure (AHF). METHODS: We reported cases of patients who presented an AHF secondary to a pheochromocytoma during a period of 10 years. The diagnosis of AHF was defined by a left ventricular ejection fraction of less than 30 % or the use of circulatory assistance. They had adrenalectomy as emergency surgery or later. Morbidity and mortality of surgery were studied. RESULTS: Thirteen patients required an adrenalectomy for AHF secondary to pheochromocytoma. Four patients (31 %) had an adrenalectomy in emergency. Nine patients (69 %) had a delayed surgery with a median delay of 25 days (7-180). Eight patients had circulatory assistance (61 %). Five of them had a circulatory assistance and a delayed surgery (38 %), two of them had a circulatory assistance followed by emergency surgery (at 1.5 and 3 days) and one had emergency surgery immediately followed by circulatory assistance. Emergency surgery was performed by laparotomy in all cases and delayed surgery by laparoscopy for seven patients (54 %). Perioperative complications consisted in: one circulatory arrest, two bleedings requiring transfusion, one intestinal ischaemia, one haemoperitoneum with re-operation (day 8). One patient died on day 5. Post-operative course of patients with delayed surgery was uneventful. CONCLUSIONS: AHF revealing a pheochromocytoma is a rare and serious event. Patients with emergency surgery have more complications than those with delayed surgery.


Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Insuficiência Cardíaca/etiologia , Feocromocitoma/complicações , Feocromocitoma/cirurgia , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
J Visc Surg ; 160(2S): S55-S62, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36774271

RESUMO

Anatomical modifications implemented during bariatric surgery not only result in weight loss, but also lead to metabolic corrections that translate into better glycemia stability and improvement in cardiovascular and liver disorders. The logical extension of surgical indications beyond mere reduction of the body mass index (BMI) (i.e. patients with<35kg/m2) is a hot topic today in France and worldwide. Metabolic surgeries make use of multiple modalities (endoscopic, mini-invasive, invasive) that should be carried out by trained physicians and within the same type of multidisciplinary formation as that for bariatric surgery. The aim of this update is to describe the physiological mechanisms that result in the benefits of bariatric surgery, the various procedures currently available and the perspectives for this new field in visceral and digestive surgery.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Humanos , Cirurgia Bariátrica/métodos , Índice de Massa Corporal , França , Obesidade Mórbida/cirurgia , Resultado do Tratamento , Redução de Peso/fisiologia
9.
Diabetologia ; 55(12): 3296-307, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22945304

RESUMO

AIMS/HYPOTHESIS: Diabetes is characterised by loss and dysfunction of the beta cell. A major goal of diabetes therapy is to promote the formation of new beta cells. Polymorphisms of T cell factor 7-like 2 (TCF7L2) are associated with type 2 diabetes, negatively regulating beta cell survival and function. Here, we provide evidence for a role of TCF7L2 in beta cell proliferation and regeneration. METHODS: Pancreatic sections from three mouse models (high-fat diet, exendin-4 and streptozotocin-treated mice) and from healthy individuals and patients with type 2 diabetes were used to investigate the association of beta cell regeneration and TCF7L2 levels. To analyse a direct effect of TCF7L2 on duct cell to beta cell conversion, TCF7L2 was overexpressed in isolated exocrine cells. RESULTS: TCF7L2 levels correlated with beta cell compensation during high-fat diet feeding. TCF7L2 was increased together with pancreatic duct cell proliferation and differentiation. Small islet-like cell clusters (ICCs) that contained TCF7L2 originated in the vicinity of the ductal epithelium. In human isolated exocrine tissue, TCF7L2 overexpression induced proliferation of pancreatic duct cells and ICC formation next to duct cells, an effect dependent on the JAK2/STAT3 pathway. CONCLUSIONS/INTERPRETATION: The present study demonstrates that TCF7L2 overexpression fosters beta cell regeneration. Our findings imply correlation of TCF7L2 levels and new beta cell formation.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Envelhecimento , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Dieta Hiperlipídica , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/metabolismo , Pâncreas/patologia , Regeneração , Transdução de Sinais
10.
Diabetologia ; 55(10): 2677-2681, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22911383

RESUMO

AIMS/HYPOTHESIS: Transcription factor 7-like 2 (TCF7L2) is a Wnt-signalling-associated transcription factor. Genetic studies have clearly demonstrated that DNA polymorphisms within TCF7L2 confer the strongest known association with increased risk of type 2 diabetes. However, the impact of the TCF7L2 type-2-diabetes-associated rs7903146 T allele on biological function and morphology of human pancreatic islets is unknown. METHODS: Paraffin sections of pancreases from 187 brain-deceased donors (HbA(1c) <6.5% [48 mmol/mol]) were used to genotype the TCF7L2 variant rs7903146 and evaluate its impact on islet morphology and alpha and beta cell subpopulations following immunostaining for glucagon and C-peptide. Following islet isolation, we investigated the correlation between TCF7L2 genotype and in vitro islet functional variables from our in-house pancreatic database. RESULTS: TCF7L2 rs7903146 (T/T) was associated with reduced basal and glucose-stimulated insulin secretion in isolated human islets, and reduced islet density in whole pancreas. Morphological analysis demonstrated islet size was increased in T/T carriers. Furthermore, rs7903146 was associated with an increased glucagon/C-peptide ratio, especially in bigger islets. CONCLUSION/INTERPRETATION: The TCF7L2 variant rs7903146 risk allele is associated with impaired insulin secretion, reduction of total islet number and quantitative as well as qualitative morphological changes in human islets. Understanding how the TCF7L2 genotype modulates its activity and how TCF7L2 impacts the islet morphology may aid the design of new therapeutic approaches for the treatment of type 2 diabetes.


Assuntos
Ilhotas Pancreáticas/patologia , Ilhotas Pancreáticas/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Alelos , Células Cultivadas , Genótipo , Glucagon/metabolismo , Células Secretoras de Glucagon/metabolismo , Células Secretoras de Glucagon/patologia , Glucose/farmacologia , Humanos , Técnicas In Vitro , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Ilhotas Pancreáticas/efeitos dos fármacos , Estudos Retrospectivos
11.
Ann Endocrinol (Paris) ; 83(6): 440-453, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36336101

RESUMO

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid with benign and non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies, the French Society of Endocrinology (SFE), the French Association of Endocrine Surgery (AFCE) and the French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This specific text is a summary chapter taking up the recommendations from specific sections and presenting algorithms for the exploration and management of thyroid nodules.


Assuntos
Endocrinologia , Medicina Nuclear , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/terapia , Nódulo da Glândula Tireoide/patologia , Consenso , Algoritmos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/patologia
12.
Diabetologia ; 54(12): 3150-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21968977

RESUMO

AIMS/HYPOTHESIS: Human adipose tissue macrophages (ATMs) display an alternatively activated (M2) phenotype, but are still able to produce excessive inflammatory mediators. However, the processes driving this particular ATM phenotype are not understood. Genome-wide association studies associated the CDKN2A locus, encoding the tumour suppressor p16(INK4A), with the development of type 2 diabetes. In the present study, p16(INK4A) levels in human ATMs and the role of p16(INK4A) in acquiring the ATM phenotype were assessed. METHODS: Gene expression of p16 ( INK4A ) in ATMs was analysed and compared with that in monocyte-derived macrophages (MDMs) from obese patients or with macrophages from human atherosclerotic plaques (AMs). Additionally, p16(INK4A) levels were studied during macrophage differentiation and polarisation of monocytes isolated from healthy donors. The role of p16(INK4A) in MDMs from healthy donors was investigated by small interfering (si)RNA-mediated silencing or adenovirus-mediated overproduction of p16(INK4A). RESULTS: Compared with MDMs and AMs, ATMs from obese patients expressed lower levels of p16 ( INK4A ). In vitro, IL-4-induced M2 polarisation resulted in lower p16(INK4A) protein levels after differentiation of monocytes from healthy donors in macrophages. Silencing of p16(INK4A) in MDMs mediated by siRNA increased the expression of M2 marker genes and enhanced the response to lipopolysaccharide (LPS), to give a phenotype resembling that of ATM. By contrast, adenovirus-mediated overproduction of p16(INK4A) in MDMs diminished M2 marker gene expression and the response to LPS. Western blot analysis revealed that p16(INK4A) overproduction inhibits LPS- and palmitate-induced Toll-like receptor 4 (TLR4)-nuclear factor of κ light polypeptide gene enhancer in B cells (NF-κB) signalling. CONCLUSIONS/INTERPRETATION: These results show that p16(INK4A) inhibits the acquisition of the ATM phenotype. The age-related increase in p16(INK4A) level may thus influence normal ATM function and contribute to type 2 diabetes risk.


Assuntos
Tecido Adiposo/metabolismo , Polaridade Celular , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Macrófagos/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Diabetes Mellitus Tipo 2/metabolismo , Regulação para Baixo , Feminino , Inativação Gênica , Humanos , Masculino , NF-kappa B/metabolismo , Obesidade/metabolismo , Placa Aterosclerótica/metabolismo , RNA Interferente Pequeno/metabolismo , Receptor 4 Toll-Like/metabolismo
13.
Diabetologia ; 54(2): 390-402, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21046358

RESUMO

AIMS/HYPOTHESIS: Glucose and incretins regulate beta cell function, gene expression and insulin exocytosis via calcium and cAMP. Prolonged exposure to elevated glucose (also termed glucotoxicity) disturbs calcium homeostasis, but little is known about cAMP signalling. We therefore investigated long-term effects of glucose on this pathway with special regard to the incretin glucagon-like peptide 1 (GLP-1). METHODS: We exposed INS-1E cells and rat or human islets to different levels of glucose for 3 days and determined functional responses in terms of second messengers (cAMP, Ca(2+)), transcription profiles, activation of cAMP-responsive element (CRE) and secretion by measuring membrane capacitance. Moreover, we modulated directly the abundance of a calcium-sensitive adenylyl cyclase (ADCY8) and GLP-1 receptor (GLP1R). RESULTS: GLP-1- or forskolin-mediated increases in cytosolic calcium, cAMP-levels or insulin secretion were largely reduced in INS-1E cells cultured at elevated glucose (>5.5 mmol/l). Statistical analysis of transcription profiles identified cAMP pathways as major targets regulated by glucose. Quantitative PCR confirmed these findings and unravelled marked downregulation of the calcium-sensitive adenylyl cyclase ADCY8 also in rat and in human islets. Re-expression of ADCY8, but not of the GLP1R, recovered GLP-1 signalling in glucotoxicity in INS-1E cells and in rat islets. Moreover, knockdown of this adenylyl cyclase showed that GLP-1-induced cAMP generation, calcium signalling, activation of the downstream target CRE and direct amplification of exocytosis by cAMP-raising agents (evaluated by capacitance measurement) proceeds via ADCY8. CONCLUSIONS/INTERPRETATION: cAMP-mediated pathways are modelled by glucose, and downregulation of the calcium-sensitive ADCY8 plays a central role herein, including signalling via the GLP1R.


Assuntos
Adenilil Ciclases/metabolismo , AMP Cíclico/metabolismo , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Glucose/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Adenilil Ciclases/genética , Animais , Cálcio/metabolismo , Linhagem Celular , Células Cultivadas , Colforsina/farmacologia , Citofotometria , Eletrofisiologia , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Células Secretoras de Insulina/enzimologia , Modelos Biológicos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Ratos , Receptores de Glucagon/genética , Receptores de Glucagon/metabolismo
14.
Minerva Endocrinol ; 36(1): 23-39, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21460785

RESUMO

Type 1 diabetes is an intrinsically unstable condition because of the loss of both insulin secretion and glucose sensing. Guidelines to treat type 1 diabetes have become stricter since results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. Therapeutic strategies first require the treatment of underlying organic causes of the brittleness associated with the optimization of insulin therapy including continuous subcutaneous insulin infusion and glucose monitoring. Alternative approaches may still be needed for the most severely affected patients. During the last decade, islet transplantation has gone from an inconsistent 1-year rate of insulin independence of 10% to 80% and could reach 50% at 5 years, at the expense of non-negligible side effects. Among potential causes of islet transplantation success, sufficient islet mass and low levels of cellular autoimmunity are of critical importance. The main issues are currently the availability of an unlimited source of insulin-secreting cells, and the immunosuppressive drug side effects. Today, islet alone and islet after kidney transplantation are offered in a limited number of isolation centres, usually in clinical trials. Islet after kidney transplantation can be considered in type 1 diabetic patients with end-stage kidney disease that are ineligible for double kidney-pancreas transplantation. Islet transplantation alone is proposed to C-peptide negative adult diabetic patients with a body weight <80 kg or low daily insulin needs with creatinine clearance above 60 ml/min, albuminuria lower than 300mg/24H and without desire for pregnancy in women. Currently and until a more complete assessment of the 5- and probably 10-year overall benefit-risk ratio is available, islet transplantation remains a clinical research procedure.


Assuntos
Diabetes Mellitus/cirurgia , Transplante das Ilhotas Pancreáticas , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Ensaios Clínicos como Assunto , Diabetes Mellitus/sangue , Diabetes Mellitus Tipo 1/cirurgia , Hemoglobinas Glicadas/metabolismo , Humanos , Imunossupressores/administração & dosagem , Células Secretoras de Insulina/metabolismo , Transplante das Ilhotas Pancreáticas/efeitos adversos , Transplante das Ilhotas Pancreáticas/tendências , Rim/fisiopatologia , Guias de Prática Clínica como Assunto , Prognóstico , Qualidade de Vida , Medição de Risco , Fatores de Risco , Resultado do Tratamento
15.
Ann Chir Plast Esthet ; 56(4): 298-307, 2011 Aug.
Artigo em Francês | MEDLINE | ID: mdl-21741144

RESUMO

BACKGROUND: Cutting the excess of skin body contouring surgery in post-massive weight loss patients seems to only improve functional and aesthetic disorders. But other benefits can be determinated such as psychosocial effects. The first two are usually evaluated. The last two are rarely researched. The goal of this study is to evaluate the benefits of body contouring surgery by comparing patient satisfaction on these different aspects. METHODS: One hundred thirty-four patients with more that 30 kg's weight loss had body contouring surgery at the university hospital in Lille between June 2004 and June 2008. Seventy-eight patients agreed to respond to a study on quality-of-life improvements after body contouring surgery which evaluated aesthetic, functional, and psychosocial aspects. The data were compared before and after the surgery to assess the benefits of the surgery in these areas. RESULTS: All the aforementioned aspects were clearly improved with the body contouring surgery. However, the improvement in the physical aspects seems to be somehow disappointing, not living up to the patients expectations. Exactly 52.5 % of the patients wanted morphologic alteration, while the scars were well tolerated in 78.2 % of the cases. On the other hand, psychosocial discomfort was improved in ways not expected by the patients. Two new findings were remarkable: a decrease of 56.7 % in the sense of feeling depressed and an improvement in finding a job after body contouring surgery. CONCLUSION: The psychosocial improvements represent the true benefits of body contouring surgery.


Assuntos
Imagem Corporal , Procedimentos Cirúrgicos Dermatológicos , Obesidade Mórbida/psicologia , Obesidade Mórbida/cirurgia , Satisfação do Paciente , Procedimentos de Cirurgia Plástica/psicologia , Redução de Peso , Índice de Massa Corporal , Depressão , Emprego , França , Hospitais Universitários , Humanos , Qualidade de Vida , Estudos Retrospectivos , Autoimagem , Inquéritos e Questionários , Fatores de Tempo
16.
Br J Surg ; 97(6): 884-91, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20473998

RESUMO

BACKGROUND: The long-term outcome of type 2 diabetes mellitus after laparoscopic adjustable gastric banding (LAGB) is unknown. METHODS: A longitudinal cohort study was undertaken of patients with grade 3 obesity and type 2 diabetes or impaired fasting glucose (IFG) undergoing LAGB. Metabolic outcomes and quality of life (QoL) were assessed before and 5 years after LAGB. RESULTS: At 5 years, data for 22 out of 23 patients with type 2 diabetes and 51 out of 53 with IFG were available. Mean(s.d.) excess weight loss was 41(25) and 41(27) per cent in patients with type 2 diabetes and IFG respectively, and was associated with a significant decrease in haemoglobin (Hb) A1c, fasting and postprandial blood glucose, insulin and triglyceride levels, and in liver steatosis. There were significant increases in insulin sensitivity, beta-cell function, disposition index, high-density lipoprotein-cholesterol and QoL (Nottingham Health Profile). Good metabolic control (HbA1c 7 per cent or less) was obtained in 13 diabetic patients, but complete diabetes remission was maintained in only four. Longer duration of diabetes, and poor preoperative glucose control and beta-cell function at baseline were associated with a less favourable outcome. CONCLUSION: LAGB improved metabolic outcomes and QoL in patients with grade 3 obesity with IFG or type 2 diabetes but rarely led to prolonged remission in long-standing diabetes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Adulto , Cirurgia Bariátrica/métodos , Diabetes Mellitus Tipo 2/metabolismo , Jejum/sangue , Feminino , Humanos , Assistência de Longa Duração , Estudos Longitudinais , Masculino , Qualidade de Vida , Redução de Peso
17.
J Visc Surg ; 157(4): 317-327, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32600823

RESUMO

Bariatric/metabolic surgery was paused during the Covid-19 pandemic. The impact of social confinement and the interruption of this surgery on the population with obesity has been underestimated, with weight gain and worsened comorbidities. Some candidates for this surgery are exposed to a high risk of mortality linked to the pandemic. Obesity and diabetes are two major risk factors for severe forms of Covid-19. The only currently effective treatment for obesity is metabolic surgery, which confers prompt, lasting benefits. It is thus necessary to resume such surgery. To ensure that this resumption is both gradual and well-founded, we have devised a priority ranking plan. The flow charts we propose will help centres to identify priority patients according to a benefit/risk assessment. Diabetes holds a central place in the decision tree. Resumption patterns will vary from one centre to another according to human, physical and medical resources, and will need adjustment as the epidemic unfolds. Specific informed consent will be required. Screening of patients with obesity should be considered, based on available knowledge. If Covid-19 is suspected, surgery must be postponed. Emphasis must be placed on infection control measures to protect patients and healthcare professionals. Confinement is strongly advocated for patients for the first month post-operatively. Patient follow-up should preferably be by teleconsultation.


Assuntos
Cirurgia Bariátrica/normas , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Controle de Infecções/normas , Obesidade/cirurgia , Pandemias/prevenção & controle , Assistência Perioperatória/normas , Pneumonia Viral/prevenção & controle , Cirurgia Bariátrica/métodos , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Procedimentos Clínicos/normas , Humanos , Controle de Infecções/métodos , Consentimento Livre e Esclarecido/normas , Obesidade/complicações , Seleção de Pacientes , Assistência Perioperatória/métodos , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , SARS-CoV-2
18.
J Chir Visc ; 157(4): 323-334, 2020 Aug.
Artigo em Francês | MEDLINE | ID: mdl-32834886

RESUMO

Bariatric/metabolic surgery was paused during the Covid-19 pandemic. The impact of social confinement and the interruption of this surgery on the population with obesity has been underestimated, with weight gain and worsened comorbidities. Some candidates for this surgery are exposed to a high risk of mortality linked to the pandemic. Obesity and diabetes are two major risk factors for severe forms of Covid-19. The only currently effective treatment for obesity is metabolic surgery, which confers prompt, lasting benefits. It is thus necessary to resume such surgery. To ensure that this resumption is both gradual and well-founded, we have devised a priority ranking plan. The flow charts we propose will help centres to identify priority patients according to a benefit/risk assessment. Diabetes holds a central place in the decision tree. Resumption patterns will vary from one centre to another according to human, physical and medical resources, and will need adjustment as the epidemic unfolds. Specific informed consent will be required. Screening of patients with obesity should be considered, based on available knowledge. If Covid-19 is suspected, surgery must be postponed. Emphasis must be placed on infection control measures to protect patients and healthcare professionals. Confinement is strongly advocated for patients for the first month post-operatively. Patient follow-up should preferably be by teleconsultation.

19.
J Visc Surg ; 157(1): 13-21, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31401070

RESUMO

BACKGROUND: Metabolic surgery is now considered as a therapeutic option in type 2 diabetes (T2D). However, few data are available regarding perioperative management of T2D. OBJECTIVES: To assess current practice among bariatric teams regarding perioperative management of T2D in order to propose guidelines. METHODS: A two-round Delphi method using online surveys was employed among bariatric teams experts (surgeons, diabetologists, anesthetists, nutritionists): first round, 63 questions covering 6 topics (characteristics of experts/teams, characteristics of patients, operative technique, pre/postoperative management, diabetes remission); second round, 44 items needing clarification. They were discussed within national congress of corresponding learned societies. Consensus was defined as ≥66% agreement. RESULTS: A total of 170 experts participated. Experts favored gastric bypass to achieve remission (76.7%). Screening for retinopathy, cardiac ultrasound, and reaching an HbA1c<8% are required in the pre-operative period for 67%, 75.3% and 56.7% of experts, respectively. After surgery, insulin pump should not be stopped, basal insulin should be halved, and bolus insulin should be stopped except if severe hyperglycemia. DPP-IV inhibitors and metformin are preferred after surgery. Patients should be seen by a diabetologist within one month if on oral antidiabetic agents (71.8% of experts), 2 weeks if on injectable treatments (77.1% of experts), and immediately after surgery if on insulin pump (93.5% of experts). Long-term monitoring of HbA1c is necessary even if diabetes remission (100%). CONCLUSION: Rapid postoperative modifications of blood glucose require a close monitoring and a prompt adjustment of diabetes medications.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/cirurgia , Cuidados Pós-Operatórios , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Glicemia/metabolismo , Técnica Delphi , Feminino , França , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade
20.
J Chir Visc ; 157(3): S44-S51, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32355510

RESUMO

The COVID-19 pandemic commands a major reorganization of the entire French healthcare system. In France, general rules have been issued nationally and implemented by each healthcare center, both public and private, throughout France. Guidelines drafted by an expert group led by the French-speaking Association of Endocrine Surgery (AFCE) propose specific surgical management principles for thyroid, parathyroid, endocrine pancreas and adrenal surgery during and after the COVID-19 epidemic.

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