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1.
iScience ; 26(11): 108190, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37953952

RESUMO

Inhibitors of neprilysin improve glycemia in patients with heart failure and type 2 diabetes (T2D). The effect of weight loss by diet, surgery, or pharmacotherapy on neprilysin activity (NEPa) is unknown. We investigated circulating NEPa and neprilysin protein concentrations in obesity, T2D, metabolic dysfunction-associated steatotic liver disease (MASLD), and following bariatric surgery, or GLP-1-receptor-agonist therapy. NEPa, but not neprilysin protein, was enhanced in obesity, T2D, and MASLD. Notably, MASLD associated with NEPa independently of BMI and HbA1c. NEPa decreased after bariatric surgery with a concurrent increase in OGTT-stimulated GLP-1. Diet-induced weight loss did not affect NEPa, but individuals randomized to 52-week weight maintenance with liraglutide (1.2 mg/day) decreased NEPa, consistent with another study following 6-week liraglutide (3 mg/day). A 90-min GLP-1 infusion did not alter NEPa. Thus, MASLD may drive exaggerated NEPa, and lowered NEPa following bariatric surgery or liraglutide therapy may contribute to the reported improved cardiometabolic effects.

2.
Gastroenterology ; 161(2): 536-547.e2, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33848536

RESUMO

OBJECTIVE: Hypothalamic melanocortin 4 receptors (MC4R) are a key regulator of energy homeostasis. Brain-penetrant MC4R agonists have failed, as concentrations required to suppress food intake also increase blood pressure. However, peripherally located MC4R may also mediate metabolic benefits of MC4R activation. Mc4r transcript is enriched in mouse enteroendocrine L cells and peripheral administration of the endogenous MC4R agonist, α-melanocyte stimulating hormone (α-MSH), triggers the release of the anorectic hormones Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in mice. This study aimed to determine whether pathways linking MC4R and L-cell secretion exist in humans. DESIGN: GLP-1 and PYY levels were assessed in body mass index-matched individuals with or without loss-of-function MC4R mutations following an oral glucose tolerance test. Immunohistochemistry was performed on human intestinal sections to characterize the mucosal MC4R system. Static incubations with MC4R agonists were carried out on human intestinal epithelia, GLP-1 and PYY contents of secretion supernatants were assayed. RESULTS: Fasting PYY levels and oral glucose-induced GLP-1 secretion were reduced in humans carrying a total loss-of-function MC4R mutation. MC4R was localized to L cells and regulates GLP-1 and PYY secretion from ex vivo human intestine. α-MSH immunoreactivity in the human intestinal epithelia was predominantly localized to L cells. Glucose-sensitive mucosal pro-opiomelanocortin cells provide a local source of α-MSH that is essential for glucose-induced GLP-1 secretion in small intestine. CONCLUSION: Our findings describe a previously unidentified signaling nexus in the human gastrointestinal tract involving α-MSH release and MC4R activation on L cells in an autocrine and paracrine fashion. Outcomes from this study have direct implications for targeting mucosal MC4R to treat human metabolic disorders.


Assuntos
Células Enteroendócrinas/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Mucosa Intestinal/metabolismo , Peptídeo YY/metabolismo , Pró-Opiomelanocortina/metabolismo , Receptor Tipo 4 de Melanocortina/metabolismo , alfa-MSH/metabolismo , Comunicação Autócrina , Glicemia/metabolismo , Estudos de Casos e Controles , Células Enteroendócrinas/efeitos dos fármacos , Glucose/administração & dosagem , Teste de Tolerância a Glucose , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mutação com Perda de Função , Comunicação Parácrina , Pró-Opiomelanocortina/genética , Receptor Tipo 4 de Melanocortina/agonistas , Receptor Tipo 4 de Melanocortina/genética , Via Secretória , Transdução de Sinais , Fatores de Tempo , alfa-MSH/farmacologia
3.
Cell Rep Med ; 1(1): 100006, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33205056

RESUMO

Individuals with obesity due to pathogenic heterozygous melanocortin 4 receptor (MC4R) mutations can be treated efficiently with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide. Here, we report the effect of 16 weeks of liraglutide 3 mg/day treatment in a woman with morbid obesity and type 2 diabetes (T2D) due to homozygous pathogenic MC4R mutation. The body weight loss was 9.7 kg, similar to weight loss in heterozygous MC4R mutation carriers and common obesity. In addition, the treatment led to clinically relevant decreases in fasting glucose, triglycerides, systolic blood pressure, and normalization of glucose tolerance. We conclude that liraglutide reduces body weight and blood glucose levels in hetero- and homozygous MC4R mutation carriers. This serves as proof-of-concept that MC4Rs are not required for the body weight and glucose lowering effects of GLP-1 RAs and that liraglutide may be used as part of the treatment of obesity and T2D due to MC4R mutations.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Liraglutida/uso terapêutico , Obesidade Mórbida/tratamento farmacológico , Receptor Tipo 4 de Melanocortina/genética , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Dinamarca , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Homozigoto , Humanos , Pessoa de Meia-Idade , Mutação , Obesidade Mórbida/complicações , Obesidade Mórbida/genética , Redução de Peso/efeitos dos fármacos
4.
J Bone Miner Metab ; 38(1): 117-125, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31471646

RESUMO

Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations. Thus, we wished to assess the impact of the MC4R on bone mass and metabolism. Secondly, we wished to investigate the impact of the GLP-1 RA liraglutide on bone mass in adults with pathogenic MC4R mutations. 17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs). Individuals with a BMI above 28 (14 MC4R mutation carriers and 28 matched control participants) underwent 16 weeks treatment with liraglutide 3.0 mg. The MC4R group had higher BMD [mean difference: 0.065 g/m2 (- 0.008 to 0.138), p = 0.03], but BMAD and BTMS were not different compared to the control group. In response to liraglutide, BMAD increased in the control group, compared to no change in the MC4R group [mean group difference: 0.0007 (0.0001-0.001), p = 0.04]. In conclusion, BMD is increased in MC4R causal obesity compared to common obesity, but when corrected for body size (BMAD), bone mass was not increased, and no evidence of an influence of the MC4R on bone metabolism in adults was found. Liraglutide treatment did not change bone metabolism in MC4R causal obesity, but increased bone mass as measured by BMAD in common obesity.


Assuntos
Estatura/genética , Osso e Ossos/patologia , Mutação/genética , Receptor Tipo 4 de Melanocortina/genética , Absorciometria de Fóton , Adulto , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Liraglutida/farmacologia , Masculino , Tamanho do Órgão/efeitos dos fármacos
5.
Cell Metab ; 28(1): 23-32.e3, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29861388

RESUMO

Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway. Thus, liraglutide could be an effective treatment of the most common form of monogenic obesity.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/genética , Receptor Tipo 4 de Melanocortina/genética , Adulto , Apetite/efeitos dos fármacos , Feminino , Humanos , Hipoglicemiantes/farmacologia , Liraglutida/farmacologia , Masculino , Pessoa de Meia-Idade , Mutação , Redução de Peso/efeitos dos fármacos
6.
Heart Rhythm ; 14(8): 1165-1170, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28400316

RESUMO

BACKGROUND: Both hypoglycemia and severe hyperglycemia constitute known risk factors for cardiac repolarization changes potentially leading to malignant arrhythmias. Patients with loss of function mutations in KCNQ1 are characterized by long QT syndrome (LQTS) and may be at increased risk for glucose-induced repolarization disturbances. OBJECTIVE: The purpose of this study was to test the hypothesis that KCNQ1 LQTS patients are at particular risk for cardiac repolarization changes during the relative hyperglycemia that occurs after an oral glucose load. METHODS: Fourteen KCNQ1 LQTS patients and 28 control participants matched for gender, body mass index, and age underwent a 3-hour oral 75-g glucose tolerance test with ECGs obtained at 7 time points. Fridericia corrected QT interval (QTcF), Bazett corrected QT interval (QTcB), and the Morphology Combination Score (MCS) were calculated. RESULTS: QTc and MCS increased in both groups. MCS remained elevated until 150 minutes after glucose ingestion, and the maximal change from baseline was larger among KCNQ1 LQTS patients compared with control subjects (0.28 ± 0.27 vs 0.15 ± 0.13; P <.05). CONCLUSION: Relative hyperglycemia induced by ingestion of 75-g glucose caused cardiac repolarization disturbances that were more severe in KCNQ1 LQTS patients compared with control subjects.


Assuntos
Glicemia/metabolismo , Eletrocardiografia/efeitos dos fármacos , Glucose/efeitos adversos , Hipoglicemia/complicações , Síndrome de Romano-Ward/complicações , Administração Oral , Adulto , Dinamarca/epidemiologia , Relação Dose-Resposta a Droga , Feminino , Glucose/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipoglicemia/sangue , Hipoglicemia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síndrome de Romano-Ward/epidemiologia , Síndrome de Romano-Ward/fisiopatologia , Edulcorantes/administração & dosagem , Edulcorantes/efeitos adversos
7.
Circulation ; 135(18): 1705-1719, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28235848

RESUMO

BACKGROUND: Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long-QT syndrome type 2 (LQT2) because of prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and ß cells and intestinal L and K cells, secreting glucagon, insulin, and the incretins glucagon-like peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide), respectively. These hormones are crucial for glucose regulation, and long-QT syndrome may cause disturbed glucose regulation. We measured secretion of these hormones and cardiac repolarization in response to glucose ingestion in LQT2 patients with functional mutations in hERG and matched healthy participants, testing the hypothesis that LQT2 patients have increased incretin and ß-cell function and decreased α-cell function, and thus lower glucose levels. METHODS: Eleven patients with LQT2 and 22 sex-, age-, and body mass index-matched control participants underwent a 6-hour 75-g oral glucose tolerance test with ECG recording and blood sampling for measurements of glucose, insulin, C-peptide, glucagon, GLP-1, and GIP. RESULTS: In comparison with matched control participants, LQT2 patients had 56% to 78% increased serum insulin, serum C-peptide, plasma GLP-1, and plasma GIP responses (P=0.03-0.001) and decreased plasma glucose levels after glucose ingestion (P=0.02) with more symptoms of hypoglycemia (P=0.04). Sixty-three percent of LQT2 patients developed hypoglycemic plasma glucose levels (<70 mg/dL) versus 36% control participants (P=0.16), and 18% patients developed serious hypoglycemia (<50 mg/dL) versus none of the controls. LQT2 patients had defective glucagon responses to low glucose, P=0.008. ß-Cell function (Insulin Secretion Sensitivity Index-2) was 2-fold higher in LQT2 patients than in controls (4398 [95% confidence interval, 2259-8562] versus 2156 [1961-3201], P=0.03). Pharmacological Kv11.1 blockade (dofetilide) in rats had similar effect, and small interfering RNA inhibition of hERG in ß and L cells increased insulin and GLP-1 secretion up to 50%. Glucose ingestion caused cardiac repolarization disturbances with increased QTc intervals in both patients and controls, but with a 122% greater increase in QTcF interval in LQT2 patients (P=0.004). CONCLUSIONS: Besides a prolonged cardiac repolarization phase, LQT2 patients display increased GLP-1, GIP, and insulin secretion and defective glucagon secretion, causing decreased plasma glucose and thus increased risk of hypoglycemia. Furthermore, glucose ingestion increased QT interval and aggravated the cardiac repolarization disturbances in LQT2 patients. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02775513.


Assuntos
Glicemia/metabolismo , Canal de Potássio ERG1/genética , Sistema de Condução Cardíaco/fisiopatologia , Hipoglicemia/etiologia , Incretinas/metabolismo , Ilhotas Pancreáticas/metabolismo , Síndrome do QT Longo/genética , Mutação , Potenciais de Ação , Adulto , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Peptídeo C/sangue , Estudos de Casos e Controles , Linhagem Celular Tumoral , Canal de Potássio ERG1/antagonistas & inibidores , Canal de Potássio ERG1/metabolismo , Eletrocardiografia , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Predisposição Genética para Doença , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Teste de Tolerância a Glucose , Sistema de Condução Cardíaco/metabolismo , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/fisiopatologia , Insulina/sangue , Síndrome do QT Longo/sangue , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Masculino , Camundongos , Pessoa de Meia-Idade , Fenótipo , Bloqueadores dos Canais de Potássio/farmacologia , Interferência de RNA , Ratos Wistar , Fatores de Tempo , Transfecção
8.
Mol Syst Biol ; 12(12): 901, 2016 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-28007936

RESUMO

Sustained weight loss is a preferred intervention in a wide range of metabolic conditions, but the effects on an individual's health state remain ill-defined. Here, we investigate the plasma proteomes of a cohort of 43 obese individuals that had undergone 8 weeks of 12% body weight loss followed by a year of weight maintenance. Using mass spectrometry-based plasma proteome profiling, we measured 1,294 plasma proteomes. Longitudinal monitoring of the cohort revealed individual-specific protein levels with wide-ranging effects of losing weight on the plasma proteome reflected in 93 significantly affected proteins. The adipocyte-secreted SERPINF1 and apolipoprotein APOF1 were most significantly regulated with fold changes of -16% and +37%, respectively (P < 10-13), and the entire apolipoprotein family showed characteristic differential regulation. Clinical laboratory parameters are reflected in the plasma proteome, and eight plasma proteins correlated better with insulin resistance than the known marker adiponectin. Nearly all study participants benefited from weight loss regarding a ten-protein inflammation panel defined from the proteomics data. We conclude that plasma proteome profiling broadly evaluates and monitors intervention in metabolic diseases.


Assuntos
Espectrometria de Massas/métodos , Obesidade/dietoterapia , Proteômica/métodos , Redução de Peso , Adulto , Apolipoproteínas/sangue , Restrição Calórica , Proteínas do Olho/sangue , Regulação da Expressão Gênica , Humanos , Resistência à Insulina , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Obesidade/metabolismo , Plasma/metabolismo , Serpinas/sangue , Adulto Jovem
9.
Eur J Endocrinol ; 174(6): 775-84, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26976129

RESUMO

OBJECTIVE: The hormones glucagon-like peptide 1 (GLP-1), peptide YY3-36 (PYY3-36), ghrelin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon have all been implicated in the pathogenesis of obesity. However, it is unknown whether they exhibit adaptive changes with respect to postprandial secretion to a sustained weight loss. DESIGN: The study was designed as a longitudinal prospective intervention study with data obtained at baseline, after 8 weeks of weight loss and 1 year after weight loss. METHODS: Twenty healthy obese individuals obtained a 13% weight loss by adhering to an 8-week very low-calorie diet (800kcal/day). After weight loss, participants entered a 52-week weight maintenance protocol. Plasma levels of GLP-1, PYY3-36, ghrelin, GIP and glucagon during a 600-kcal meal were measured before weight loss, after weight loss and after 1 year of weight maintenance. Area under the curve (AUC) was calculated as total AUC (tAUC) and incremental AUC (iAUC). RESULTS: Weight loss was successfully maintained for 52 weeks. iAUC for GLP-1 increased by 44% after weight loss (P<0.04) and increased to 72% at week 52 (P=0.0001). iAUC for PYY3-36 increased by 74% after weight loss (P<0.0001) and by 36% at week 52 (P=0.02). tAUC for ghrelin increased by 23% after weight loss (P<0.0001), but at week 52, the increase was reduced to 16% compared with before weight loss (P=0.005). iAUC for GIP increased by 36% after weight loss (P=0.001), but returned to before weight loss levels at week 52. Glucagon levels were unaffected by weight loss. CONCLUSIONS: Meal responses of GLP-1 and PYY3-36 remained increased 1 year after weight maintenance, whereas ghrelin and GIP reverted toward before-weight loss values. Thus, an increase in appetite inhibitory mechanisms and a partly decrease in appetite-stimulating mechanisms appear to contribute to successful long-term weight loss maintenance.


Assuntos
Peptídeo 1 Semelhante ao Glucagon/sangue , Fragmentos de Peptídeos/sangue , Peptídeo YY/sangue , Período Pós-Prandial/fisiologia , Redução de Peso/fisiologia , Adaptação Fisiológica/fisiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
J Clin Endocrinol Metab ; 100(8): 2909-17, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26043228

RESUMO

CONTEXT: Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. OBJECTIVE: To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction. DESIGN: Randomized control study. SETTING: Outpatient research hospital clinic. PARTICIPANTS: Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m(2) and age 46 ± 2 years. INTERVENTION: After a low-calorie-diet-induced 12% weight loss, participants were randomized to treatment with or without administration of the GLP-1 RA liraglutide (1.2 mg/d) for 52 weeks. In case of weight gain, up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss. MAIN OUTCOME MEASURES: Total, pelvic, and arm-leg bone mineral content (BMC) and bone markers [C-terminal telopeptide of type 1 collagen (CTX-1) and N-terminal propeptide of type 1 procollagen (P1NP)] were investigated before and after weight loss and after 52-week weight maintenance. Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment. RESULTS: Total, pelvic, and arm-leg BMC decreased during weight maintenance in the control group (P < .0001), but not significantly in the liraglutide group. Thus, total and arm-leg BMC loss was four times greater in the control group compared to the liraglutide group (estimated difference, 27 g; 95% confidence interval, 5-48; P = .01), although the 12% weight loss was maintained in both groups. In the liraglutide group, the bone formation marker P1NP increased by 16% (7 ± 3 µg/L) vs a 2% (-1 ± 4 µg/L) decrease in the control group (P < .05). The bone resorption marker CTX-1 collagen did not change during the weight loss maintenance phase. CONCLUSIONS: Treatment with a long-acting GLP-1 RA increased bone formation by 16% and prevented bone loss after weight loss obtained through a low-calorie diet, supporting its role as a safe weight-lowering agent.


Assuntos
Reabsorção Óssea/prevenção & controle , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Obesidade/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Receptores de Glucagon/agonistas , Redução de Peso , Adolescente , Adulto , Idoso , Reabsorção Óssea/etiologia , Restrição Calórica/efeitos adversos , Feminino , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Liraglutida , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/fisiopatologia , Redução de Peso/efeitos dos fármacos , Redução de Peso/fisiologia , Adulto Jovem
11.
Expert Opin Pharmacother ; 15(17): 2487-500, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25260877

RESUMO

INTRODUCTION: The dramatic rise in the prevalence of obesity and type 2 diabetes mellitus (T2DM) is associated with increased mortality, morbidity as well as public health care expenses worldwide. The need for effective and long-lasting pharmaceutical treatment is obvious. The record of anti-obesity drugs has been poor so far and the only efficient treatment today is bariatric surgery. Research has indicated that appetite inhibiting hormones from the gut may have a therapeutic potential in obesity. The gut incretin hormone, glucagon-like peptide-1 (GLP-1), appears to be involved in both peripheral and central pathways mediating satiety. Clinical trials have shown that two GLP-1 receptor agonists exenatide and liraglutide have a weight-lowering potential in non-diabetic obese individuals. Furthermore, they may also hold a potential in preventing diabetes as compared to other weight loss agents. AREAS COVERED: The purpose of this review is to cover the background for the GLP-1-based therapies and their potential in obesity and pre-diabetes. Up-to-date literature on incretin-based therapies will be summarized with a special mention of their weight-lowering properties. The literature updated to August 2014 from PubMed was identified using the combinations: GLP-1, GLP-1 receptor agonists, incretins, obesity and pre-diabetes. EXPERT OPINION: The incretin impairment, which seems to exist in both obesity and diabetes, may link these two pathologies and underlines the potential of GLP-1-based therapies in the prevention and treatment of these diseases.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipoglicemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Receptores de Glucagon/agonistas , Apetite/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/prevenção & controle , Exenatida , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Incretinas/metabolismo , Liraglutida , Obesidade/metabolismo , Peptídeos/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/metabolismo , Peçonhas/uso terapêutico
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