Recomendaciones de expertos acerca del uso de teduglutide en pacientes pediátricos con sindrome de intestino corto / Expert recommendations on the use of teduglutide in pediatric patients with short bowel syndrome

Resumen El síndrome de intestino corto es una entidad de baja incidencia en los pacientes pediátricos, pero se asocia con elevadas tasas de morbimortalidad. El abordaje de estos pacientes por un equipo interdisciplinario de expertos enfocados en la rehabilitación intestinal mejora los resultados a corto y a largo plazo. Entre los recursos disponibles para el tratamiento se incluye el teduglutide, un análogo del péptido similar al glucagón tipo 2 (GLP-2) elaborado mediante técnicas recombinantes. Por medio de la aplicación del método Delphi, a partir de la evidencia disponible y de la experiencia de los autores, se proponen recomendaciones para el uso de teduglutide, dirigidas a los profesionales de la salud que tratan a los pacientes pediátricos con síndrome de intestino corto, así como a las autoridades sanitarias.

Abstract Short bowel syndrome is a low-incidence disorder among pediatric patients, but it is associated with high morbidity and mortality rates. Management of these patients by an interdisciplinary team of experts focused on intestinal rehabilitation improves short- and long-term outcomes. Available resources for treatment include teduglutide, a glucagon-like peptide type 2 (GLP-2) analog made by recombinant techniques. Considering the available evi dence and the authors' experience, Delphi-based recommendations for the use of teduglutide are suggested for healthcare professionals who treat pediatric patients with short bowel syndrome, as well as for health authorities.

Rehabilitación del intestino utilizando un análogo semisintético del péptido 2 similar al glucagón. Primera experiencia con teduglutide en Uruguay / Intestinal rehabilitation using semisynthetic glucagon-like peptide-2 analogue. First experience with teduglutide in Uruguay / Reabilitação do intestino usando um análogo semi-sintético do peptídeo 2 semelhante ao glucagon. Primeira experiência com teduglutide no Uruguai

Resumen: La falla intestinal crónica (FIC) o tipo III es una condición invalidante, y la nutrición parenteral crónica (NPC) domiciliaria es el tratamiento que permite a estos pacientes mantenerse con vida. Sin embargo, solamente uno de cada tres países latinoamericanos cuentan con ese recurso, y sus complicaciones no son infrecuentes. Estas complicaciones son las principales indicaciones para trasplante intestinal, un procedimiento que en la mayoría de los países de ingresos medios no se ha desarrollado y no ha presentado los resultados esperados. En los últimos años, la rehabilitación intestinal a nivel mundial ha mejorado sustancialmente con el uso de análogos semisintéticos del péptido 2 similares al glucagón, existiendo cada vez mayor evidencia que demuestra la posibilidad de rehabilitación intestinal e independencia de la NPC con este fármaco, incluso en pacientes con anatomía desfavorable. Estos resultados han permitido mejorar la supervivencia y la calidad de vida de pacientes con FIC y, en muchas ocasiones, prescindir del trasplante. El paciente del caso que presentamos es el primero en recibir esta terapéutica en nuestro país. En este artículo analizamos la respuesta precoz favorable al tratamiento y sus perspectivas a futuro.

Abstract: Long-term home parenteral nutrition (HPN) is a life-saving treatment for patients with chronic intestinal failure, an invalidating condition. However, only 1 out of 3 countries can rely on this treatment and complications associated to chronic parenteral nutrition are rather frequent. The latter constitute the main indication for intestinal transplantion, a procedure that in most middle-income countries has not yet developed and has not shown the expected outcome. In recent years, intestinal rehabilitation has significantly improved at the global level with the use of GLP2, based on the growing evidence that proves the possibility of intestinal rehabilitation and independence from parenteral nutrition with Teduglutide, even in the case of patients with unfavorable anatomy. These results have caused a positive impact on survival and the quality of life of patients with chronic renal failure, and they can often abstain from transplant. The patient of the case study is the first one who received this therapy in our country and this article analyses his favorable early response to treatment and future perspectives.

Resumo: A insuficiência intestinal crônica (CIF) ou tipo III é uma condição incapacitante e a nutrição parenteral crônica (NPC) domiciliar é o tratamento que permite a sobrevida desses pacientes. No entanto, apenas 1 em cada 3 países latino-americanos dispõe desse recurso e as complicações da NPC não são raras. Essas complicações são as principais indicações para o transplante intestinal, procedimento que na maioria dos países de renda média não foi desenvolvido ou não apresentou os resultados esperados. Nos últimos anos, a reabilitação intestinal em todo o mundo tem melhorado substancialmente com o uso de sGLP2, com um número cada vez maior de evidências que mostram a possibilidade de reabilitação intestinal e independência da NPC, mesmo em pacientes com anatomia desfavorável. Esses resultados têm possibilitado prolongar a sobrevida e melhorar a qualidade de vida dos pacientes com CIF e, em muitos casos, dispensar o transplante. O paciente do caso que apresentamos é o primeiro a receber essa terapia em nosso país. Neste artigo, analisamos a resposta favorável ao tratamento precoce e suas perspectivas futuras.

Clinical effects of Metformin combined with a Glucagon-like peptide-1 analogue on type 2 diabetes in elderly patients / 中华老年医学杂志

Objective:To investigate the therapeutic effects of Metformin combined with a glucagon-like peptide-1(GLP-1)analogue on type 2 diabetes mellitus and immune cell function in elderly patients.Methods:A total of 180 elderly obese patients with type 2 diabetes mellitus treated in our hospital from November 2018 to November 2020 were included.They were divided into the control group(n=90, treated with Metformin)and the observation group(n=90, taking the GLP-1 analogue liraglutide in addition to Metformin). The two groups of patients were compared on body mass index(BMI), waist-to-hip ratio, glycosylated hemoglobin(HbA1c), fasting blood glucose(FBG), 2 hour postprandial blood glucose(2h-PBG), triglycerides(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C)and islet cell function(homeostatic model assessment of β-cell function, HOMA-β).Results:After treatment, BMI and waist-to-hip ratio decreased more significantly in the observation group than in the control group( P<0.05). HbA1c, FBG and 2H PBG levels were lower in the observation group than in the control group after treatment[(8.81±1.48)% vs.(10.6±1.94)%, (5.54±1.03)mmol/L vs.(6.91±1.10)mmol/L, (7.13±1.27)mmol/L vs.(8.86±1.74)mmol/L, all P<0.05]. After treatment, the observation group had more significantly decreased TG and TC levels and increased HDL-C levels than the control group( P<0.05). Changes in HOMAIR and HOMA-β in the observation group were more evident than in the control group after treatment( P<0.05). The incidence of adverse reactions during treatment was significantly lower in the observation group than in the control group(11.1% vs.31.1%, P<0.05). Conclusions:Metformin combined with a GLP-1 analogue has clearly favorable effects on T 2DM in elderly patients with obesity, helps achieve good blood glucose control and is very safe to use.The combination therapy can significantly restore the function of islet cells in patients with diabetes and delay the progression of diabetes.

Comparação dos níveis de proteína C reativa, GLP-1 e GLP-2 entre indivíduos diabéticos, obesos mórbidos e controles saudáveis: um estudo exploratório / Comparison of the levels of c-reactive protein, glp-1 and glp-2 among individuals with diabetes, morbid obesity and healthy controls: an exploratory study

ABSTRACT BACKGROUND: The glucagon-like peptides 1 and 2 (GLP-1/GLP-2) are gut hormones that may directly affect the glucose homeostasis and their activity seems to be significantly affected by chronic inflammation. OBJECTIVE: To evaluate the postprandial levels of glucagon-like peptides 1 and 2 (GLP-1/GLP-2), C-reactive protein (CRP), and the postprandial glucose and insulin levels among individuals with obesity, type 2 diabetes, and healthy controls. METHODS: An exploratory cross-sectional study, which involved individuals awaiting for bariatric/metabolic surgery and healthy controls. Postprandial levels of GLP-1, GLP-2, glucose, and insulin were obtained after a standard meal tolerance test. Inflammation was assessed by means of CRP. RESULTS: There were 30 individuals enrolled in the study, divided into three groups: non-diabetic with morbid obesity (NDO; n=11 individuals), diabetic with mild obesity (T2D; n=12 individuals), and healthy controls (C; n=7 individuals). The mean CRP levels were significantly higher in the NDO group (6.6±4.7 mg/dL) than in the T2D (3.3±2.2 mg/dL) and C groups (2.5±3.2 mg/dL) (P=0.038). The GLP-1 levels following standard meal tolerance test and the area under the curve of GLP-1 did not differ among the three groups. The GLP-2 levels were significantly lower in the NDO and T2D than in the C group following standard meal tolerance test at all the times evaluated. The area under the curve of the GLP-2 was significantly lower in the NDO and T2D groups than in the C group (P=0.05 and P=0.01, respectively). CONCLUSION: GLP-2 levels were impaired in the individuals with obesity and diabetes. This mechanism seems to be enrolled in preventing the worsening of the glucose homeostasis in these individuals.

RESUMO CONTEXTO: Os peptídeos semelhantes ao glucagon 1 e 2 (GLP-1/GLP-2) são hormônios gastrointestinais que podem afetar diretamente a homeostase glicêmica; a atividade de ambos parece ser significativamente afetada pela inflamação crônica. OBJETIVO: Avaliar os níveis pós-prandiais dos peptídeos semelhantes ao glucagon 1 e 2 (GLP-1/GLP-2), proteína C reativa (PCR) e as curvas pós-prandiais de glucose e insulina entre indivíduos com obesidade, diabetes tipo 2 e controles saudáveis. MÉTODOS: Estudo piloto transversal, que envolveu indivíduos aguardando a realização de cirurgia bariátrica/metabólica e controles saudáveis. Os níveis de GLP-1, GLP-2, glucose e insulina foram obtidos após um teste de refeição padrão. A inflamação foi avaliada através dos níveis de PCR. RESULTADOS: Houve 30 indivíduos avaliados no estudo, divididos em três grupos: obesos mórbidos sem diabetes (NDO; n=11 pacientes), diabéticos com obesidade leve (T2D; n=12 pacientes) e controles (C; n=7 pacientes). Os níveis médios de PCR foram significativamente maiores no grupo NDO (6,6±4,7 mg/dL) do que nos grupos T2D (3,3±2,2 mg/dL) e C (2,5±3,2 mg/ dL) (P=0,038). Os níveis de GLP-1 após o teste de refeição padrão e a área sob a curva do GLP-1 não diferiram significativamente entre os grupos. Os níveis de GLP-2 foram significativamente mais baixos nos grupos NDO e T2D do que no grupo C em todos os tempos avaliados. A área sob a curva do GLP-2 foi significativamente menor nos grupos NDO e T2D do que no grupo C (P=0,05 and P=0,01, respectivamente). CONCLUSÃO: Os níveis de GLP-2 encontram-se alterados em indivíduos com obesidade e diabetes. Este mecanismo parece estar envolvido na prevenção da piora da homeostase glicêmica nestes indivíduos.

Intestinal inflammatory and redox responses to the perioperative administration of teduglutide in rats

Abstract Purpose: To investigate the inflammatory and redox responses to teduglutide on an animal model of laparotomy and intestinal anastomosis. Methods: Wistar rats (n=62) were allocated into four groups: "Ileal Resection and Anastomosis" vs. "Laparotomy", each one split into "Postoperative Teduglutide Administration" vs. "No Treatment"; and euthanized at the third or the seventh day. Ileal and blood samples were recovered at the baseline and at the euthanasia. Flow cytometry was used to study the inflammatory response (IL-1α, MCP-1, TNF-α, IFN-γ and IL-4 levels), oxidative stress (cytosolic peroxides, mitochondrial reactive species, intracellular glutathione and mitochondrial membrane potential) and cellular viability and death (annexin V/propidium iodide double staining). Results: Postoperative teduglutide treatment was associated with higher cellular viability index and lower early apoptosis ratio at the seventh day; higher cytosolic peroxides level at the third day and mitochondrial overgeneration of reactive species at the seventh day; higher tissue concentration of IL-4 and lower local pro-to-anti-inflammatory cytokines ratio at the seventh day. Conclusion: Those findings suggest an intestinal pro-oxidative and anti-inflammatory influence of teduglutide on the peri-operative context with a potential interference in the intestinal anastomotic healing.

GLP-2: a poorly understood mediator enrolled in various bariatric/metabolic surgery-related pathophysiologic mechanisms / GLP-2: um mediador pouco compreendido envolvido em diversos mecanismos fisiopatológicos relacionados à cirurgia bariátrica/metabólica

ABSTRACT Introduction: Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone whose effects are predominantly trophic on the intestinal mucosa. Aim: Critically evaluate the current literature on the influence of bariatric/metabolic surgery on the levels of GLP-2 and its potential clinical implications. Method s: Narrative review through online research on the databases Medline and Lilacs. There were six prospective human studies, two cross-sectional human studies, and three experimental animal studies selected. Results: There is evidence demonstrating significant increase in the levels of GLP-2 following gastric bypass, Scopinaro operation, and sleeve gastrectomy. There are no differences between gastric bypass and sleeve gastrectomy in regards to the increase in the GLP-2 levels. There is no correlation between the postoperative levels of GLP-2 and the occurrence of adequate or insufficient postoperative weight loss. Conclusion: GLP-2 plays significant roles on the regulation of nutrient absorption, permeability of gut mucosa, control of bone resorption, and regulation of satiety. The overall impact of these effects potentially exerts a significant adaptive or compensatory effect within the context of varied bariatric surgical techniques.

RESUMO Introdução: O peptídeo semelhante ao glucagon-2 (GLP-2) é hormônio gastrointestinal com efeitos predominantemente tróficos sobre a mucosa intestinal. Objetivo: Avaliar criticamente a literatura atual a respeito da cirurgia bariátrica/metabólica sobre os níveis de GLP-2 e suas potenciais implicações clínicas. Métodos: Revisão narrativa realizada através de pesquisa on-line nas bases de dados Medline e LILACS. Foram selecionados seis estudos prospectivos em humanos, dois transversais em humanos e três experimentais em animais. Resultados: Existem evidências demonstrando aumento significativo nos níveis de GLP-2 após o bypass gástrico, a operação de Scopinaro e a gastrectomia vertical. Não foram observadas diferenças entre o bypass gástrico e a gastrectomia vertical em relação ao aumento do GLP-2. Não há correlação entre os níveis de GLP-2 e a ocorrência de perda de peso pós-operatória adequada ou insuficiente. Conclusão: O GLP-2 desempenha importantes papel sobre a regulação da absorção de nutrientes, permeabilidade da mucosa intestinal, controle da reabsorção óssea e regulação da saciedade. O impacto combinado destes efeitos potencialmente exerce efeito adaptativo ou compensatório importante no contexto das diferentes técnicas bariátricas.

Correlation between pre and postoperative levels of glp-1/glp-2 and weight loss after roux-en-y gastric bypass: a prospective study / Correlação entre os níveis pré e pós-operatórios de glp-1/glp-2 e a perda de peso após o bypass gástrico em y-de-roux: um estudo prospectivo

ABSTRACT Background: The role of gut hormones in glucose homeostasis and weight loss achievement and maintenance after bariatric surgery appears to be a key point in the understanding of the beneficial effects observed following these procedures. Aim: To determine whether there is a correlation between the pre and postoperative levels of both GLP-1 and GLP-2 and the excess weight loss after Roux-en-Y gastric bypass (RYGB). Methods: An exploratory prospective study which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months. GLP-1 and GLP-2 after standard meal tolerance test (MTT) were determined before and after surgery and then correlated with the percentage of excess loss (%EWL). Results: GLP-2 AUC presented a significant postoperative increase (945.3±449.1 vs.1787.9±602.7; p=0.0037); GLP-1 AUC presented a non-significant trend towards increase after RYGB (709.6±320.4 vs. 1026.5±714.3; p=0.3808). Mean %EWL was 66.7±12.2%. There was not any significant correlation between both the pre and postoperative GLP-1 AUCs and GLP-2 AUCs and the %EWL achieved after one year. Conclusion: There was no significant correlation between the pre and postoperative levels of the areas under the GLP-1 and GLP-2 curves with the percentage of weight loss reached after one year.

RESUMO Racional: O papel de hormônios gastrointestinais sobre a homeostase glicêmica e a obtenção e manutenção da perda de peso após a cirurgia bariátrica parece ser elemento fundamental na compreensão dos benefícios observados após estes procedimentos. Objetivo: Determinar se há correlação entre os níveis pré e pós-operatórios de GLP-1 e GLP-2 com a perda do excesso de peso após o bypass gástrico em Y-de-Roux. Métodos: Estudo prospectivo exploratório que envolveu 11 indivíduos submetidos ao bypass gástrico, acompanhados por 12 meses. Os níveis GLP-1 e GLP-2 após um teste de refeição padrão foram determinados antes e 12 meses após a operação e então foram correlacionados com o percentual de perda do excesso de peso. Resultados: Houve aumento significativo da área sob a curva do GLP-2 após a operação (945,3±449,1 vs. 1787,9±602,7; p=0,0037); a área sob a curva do GLP-1 apresentou tendência não-significativa à elevação após o procedimento (709,6±320,4 vs. 1026,5±714,3; p=0,3808). O percentual médio de perda de peso foi 66,7±12,2%. Conclusão: Não houve nenhuma correlação significativa entre os níveis pré e pós-operatórios das áreas sob as curvas de GLP-1 e GLP-2 com o percentual de perda de peso atingido após um ano.

O papel dos hormônios entéricos GLP-2 e serotonina no metabolismo ósseo de mulheres pós-menopausadas portadoras de Diabetes Mellitus tipo 2 / The role of enteric hormones GLP-2 and serotonina on bone metabolism in postmenopausal women with type 2 diabetes

O diabetes mellitus (DM) é uma doença metabólica associada a danos, disfunção e insuficiência de diversos órgãos, sendo a fragilidade óssea apontada por estudos recentes como também associada ao DM. Os mecanismos que justificam o maior risco de fraturas em diabéticos tipo 2 não são bem compreendidos. A influência do trato gastrointestinal e seus hormônios no remodelamento ósseo tem sido comprovada em animais e em indivíduos sadios, sendo o Glucagon-like peptide-2 (GLP-2) e a serotonina hormônios com produção intestinal estimulada pela ingestão de nutrientes, existindo algumas evidências de que os mesmos têm efeitos no metabolismo ósseo. O presente estudo comparou a dinâmica dos marcadores ósseos, da serotonina e do GLP-2 em resposta à refeição mista em mulheres pósmenopausadas diabéticas em relação a controles não diabéticas. Foram incluídas 43 mulheres pós-menopausadas com densidade mineral óssea (DMO) reduzida, 23 com diabetes (grupo DM) e 20 controles (grupo CO). Depois do jejum de 12 horas, essas mulheres foram submetidas ao teste de refeição padrão, e as amostras de sangue foram coletadas nos tempos 0, 30, 60, 120 e 180 minutos para a dosagem de telopeptídeo C-terminal do colágeno tipo I sérico (CTX), osteocalcina (OC), GLP-2 e serotonina. O grupo DM apresentou maior índice de massa corporal, bem como maior densidade mineral óssea (DMO) de colo de fêmur e quadril. Nos tempos basais as mulheres diabéticas apresentaram concentrações plasmáticas de LH e FSH, bem como dos marcadores ósseos osteocalcina e CTX menores que no grupo CO. Em resposta a refeição padrão houve, em ambos os grupos, diminuição na concentração do CTX e da osteocalcina, e aumento na de GLP-2, sem alteração significativa da serotonina. A resposta do CTX à refeição foi menor no grupo DM, e a da serotonina maior no grupo CO em um único tempo do teste. Em relação a OC e ao GLP-2, não houve diferença entre os grupos avaliados ao longo do teste de refeição. As mulheres...

Type 2 diabetes mellitus is metabolic disease associated with long-term damage, dysfunction, and failure of various organs; recent studies indicate that diabetes itself is associated with bone fragility. The mechanisms underlying the increased fracture risk in type 2 diabetes are not well understood. The influence of the gastrointestinal tract and its hormones in bone remodeling has been demonstrated in animals and in healthy subjects. Glucagon-like peptide-2 (GLP-2) and serotonin are enteric hormones stimulated by nutrient intake, and there is some evidence that these hormones could have some effects on bone metabolism. We studied the dynamics of bone markers, serotonin and GLP- 2 in response to a mixed meal in diabetic postmenopausal women, in comparison with nondiabetic controls. 43 post-menopausal women with reduced bone mineral density (BMD) were enrolled, 23 with diabetes (DM group) and 20 normal control (CO group). After an overnight fast (12h), subjects were submitted to a standard meal test. Blood samples were drawn for C-terminal crosslinked telopeptide (CTX), osteocalcin (OC), GLP-2 and serotonin at 0, 30, 60, 120 and 180 minutes. The DM group had higher body mass index, and higher BMD of the femoral neck and hip. The basal values of of LH and FSH as well as the bone markers osteocalcin and CTX were lower in the DM group than in the CO group. After the standard meal test, there was a decrease in the concentration of CTX and osteocalcin, and an increase in GLP-2 in both groups. No changes in concentrations of serotonin were observed over the test meal. The response of the CTX meal was lower in the DM group, and the serotonin concentration was greater in the CO group in a single test time. In relation to e OC and GLP-2, there were no differences among the groups throughout the test meal. Type 2 diabetic women had higher bone mineral density (BMD) in the femur. Furthermore, the results suggest that the bone remodeling of diabetic women...

Changes of glucagon-like peptide-2 expression in serum and ileum after colectomy in rats / 中华实用儿科临床杂志

Objective To explore the effect of colectomy on the expression of glucagon-like peptide-2 (GLP-2) in serum and ileum and compare the changes of GLP-2 after different colectomy in rats.Methods Eighty male or female rats,aging 3-4 months old,were recruited in this study.The rats weight 180-250 g.The 80 rats were evenly and randomly distributed into 4 groups according to the surgical procedures they underwent:control group,in which the rats were not performed any procedures; sham surgery group,in which the rats underwent laparotomy ;left hemicolectomy group,in which the rats were performed left hemicolectomy;and subtotal colectomy group,in which the rats were performed subtotal colectomy.According to execution time,each group had 4 subgroups,including 0 day group,10 day group,20 day group and 30 day group,and 5 rats were included in each subgroup.The whole blood was collected through cardiac puncture.Serum was collected and GLP-2 in serum was determined by enzyme-linked immunosorbent assay.The GLP-2 in ileum was studied by immunohistochemistry staining.The length of villus of ileum was also measured by HE staining.Results The protein of GLP-2 was found in fibroblasts,epithelium and endocrine cells in ileum.Compared with control group and sham surgery group,the expressions of GLP-2 in serum and ileum increased significantly in the rats that underwent left hemicolectomy after surgery(all P ＜ 0.05),and it was increasing with time.The villus length of the rats underwent left hemicolectomy also increased significantly compared with the control group and sham surgery groups 20 days and 30 days after surgery(all P ＜ 0.05).The expressions of GLP-2 in serun and ileum and villus length of the rats with subtotal colectomy were not significantly different from those of the control group and sham surgery group(all P ＞ 0.05).Conclusions The expressions of GLP-2 in serum and ileum are elevated after left hemicolectomy but not in subtotal colectomy,which may be related to the delayed intestinal adaption after colectomy.

The protective effect of glucagon-like peptide-2(GLP-2) on intestinal barrier function in bile duct ligated rats / 中华肝胆外科杂志

ObjectiveTo investigate the effect of glucagon-like peptide-2(GLP-2) on intestinal barrier function in the bile duct ligated rats.MethodsSeventy-two SD rats were randomly divided into three groups:GLP-2 treated group(T group),obstructive jaundice control group (C group) and sham operation group (SO group).The mRNA expression of GLP-2R was measured by semi-quantified reverse transcription polymerase chain reaction (RT-PCR)and the bcl-2 expression in the intestinal mucosa was measured by immunohistochemistry staining equipped image analyzing systems (Image proplus Version 4.5).ResultsThe mRNA expression of GLP-2 in intestinal mucosa in T group was higher than that in C group (P＜0.05) but lower than that in SO group (P＞0.05).The expression of bcl-2 in the intestinal villi of rats in C group showed more significant decrease (P＜0.05) than those in the SO and T groups especially on day 3 and 7 after operation (P＜0.05).ConclusionsGLP-2 may increase the mRNA expression of GLP-2R,stimulate the growth of intestinal mucosa,diminish the number of the apoptosis cells,and protect the intestinal barrier function in obstructive jaundice rats.

Glucagon-like peptide 2 and treatment for osteoporosis / 国际药学研究杂志

Glucagon-like peptide 2 (GLP-2), as an important gastrointestinal growth factor, has many physiological effects. Exogenous GLP-2 can effectively treat the osteoporosis. The results of clinical trials show that GLP-2 can reduce bone resorption in a dose-dependent manner, but has no effect on bone formation. Integrity of gastrointestinal tract is necessary for its therapeutic effect. This article summarizes the research advances in synthesis, secretion, metabolism and signal transduction of GLP-2 and reviews the safety and tolerability of exogenous GLP-2 in clinical application.

Progress in the biology of glucagon-like peptide 2 / 中国药理学通报

Glucagon-like peptide-2 (GLP-2) is a 33-amino acid peptide derived from the tissue-specific, post-translational processing of the proglucagon gene.GLP-2 is a newly discovered,specific for the intestine growth factor that affects gastrointestinal functions including epithelial growth of normal and developing intestinal preventing damage and facilitating intestinal repair in animal models and patients of intestinal disease. GLP-2 also inhibits gastrointestinal motility and gastric acid secretion, up-regulates intestinal blood flow and reduces food intake. The actions of GLP-2 are initiated by activation of the GLP-2 receptor (GLP-2R), a specific G-protein-linked membrane receptor. This review provides an overview of the physiological, pharmacological, and therapeutic actions of GLP-2 and GLP-2R signaling mechanism, with a focus on the most recent findings on the role of this peptide hormone in the normal and diseased gastrointestinal tract.

Effects of GLP-2 on the mRNA expression of GLP-2R and PG in postburn rats / 第三军医大学学报

Objective To investigate the effects of glucagon like peptide 2(GLP 2) on the mRNA expressions of GLP 2 receptor (GLP 2R) and proglucagon gene(PG) in postburn rats. Methods A total of 55 Wistar rats were randomly divided into three groups including burn group, GLP 2 treatment group(treated with GLP 2, 200 ?g/kg, b.i.d ) and normal control group. Rats were sacrificed at 6, 12 h and 1, 3 and 5 d after burn injury. The proliferating cell nuclear antigen(PCNA) expression and the histological changes of the intestinal mucosa were determined by immunohistochemical staining. mRNA expressions of GLP 2R and PG were detected by RT PCR at 6, 12 h and 1, 3 and 5 d after burn injury. Results The expression of PCNA in rat intestinal mucosa decreased at 1 d after burn injury, but it was stronger in GLP 2 treatment group than that in burn group. Histological observation revealed that intestinal villi in GLP 2 treatment group were regularly arranged without obvious epithelial shedding. PG mRNA expression peaked at 12 h, 1 and 3 d after burn injury. No change of PG mRNA expression was found after treatment with GLP 2. Decreased GLP 2R mRNA expression was found in postburn rats, but after treatment with GLP 2, increased GLP 2R mRNA expression was found. Conclusion GLP 2 supplementation can keep the structure of the postburn rat intestinal mucosa without affecting PG gene expression. The mechanism may probably be related to the promotion of the mRNA expression of GLP 2R of the intestinal mucosa in rats.

Effects of glucagon-like peptide 2 on the absorption-related genes expressionsof residual small bowel in a rat model of short bowel syndrome / 中华消化杂志

Objective To study the effect of glucagon-like peptide 2 (GLP-2) on the absorption- related genes [ sodium dependent glucose transporter 1 (SGLT1) and dipeptide transporter 1 (PEPT1)] mRNA expressions of residual small bowel in a rat model of short bowel syndrome. Methods Rats undertaken 75% small bowel resection were randomly assigned into 3 groups: short bowel control (SBC) group, growth hormone (GH) group and GLP-2 group. Another weight-matched normal rats with normal diet was used as normal (NC) group. All rats were given normal chow on the 1st postoperative day (POD). On the 6th POD, partial segment of terminal ileum was harvested to evaluate the mRNA expressions of SGLT1 and PEPT1 by semiquantified reverse transcription polymerase chain reaction. Results The mRNA expressions of both SGLT1 and PEPT1 in SBC group were significantly higher than that of NC group(P0.05). Conclusions A short term GLP-2 adiministration in early postoperative days may has no significant effect on mRNA expressions of SGLT1 and PEPT1 in residual ileum in rats with short bowel syndrome.

The effects of glucagon-like peptide-2 on the intestinal epithelium MLCK in rats with obstructive jaundice / 中国普通外科杂志

Objective To explore the effects of glucagon-like peptide-2(GLP-2) on intestinal mucosa epithelium myosin light chain kinase(MLCK)of the rat with obstructive jaundice.Methods The obstructive jaundice models of rats were set up.At postoperative 10 d,the control group rats were subcutaneously injected with 0.5 mL PBS;experiment group A with 250g/(kg?d) GLP-2 (0.5 mL),and experiment group B with 125 g/(kg?d) GLP-2 (0.5 mL),b.i.d?7 d,then all the rats were killed The villus height,mucosa thickness and crypt depth of the terminal ileum mucosa were detected.Immunohistochemistry and Western-blot were used to examine the distribution and expression of MLCK.Image analytical system and statistics software were used to analyze the results quantitately.Results The intestinal villi of the distal ileum mucosa were short and sparse in control group.Compared with control group,the average intestinal villus height,mucosa thickness and crypt depth were increased 27.8%,21.7% and 25.4%(all P0.05).The same outcomes were obtained by quantitative analysing Western blot images.The degression of intestinal villus height and absorbance of MLCK images presented direct correlation.Conclusions The intestinal mucous membrane shows obvious atrophy in obstructive jaundice.Exogenous supplemented GLP-2 can enhance the quantity and distribution of MLCK in intestinal mucosa in obstructive jaurdice,and can restore the morphology of intestinal mucosa epithelium.