Diagnostic value of serum levels of galanin and obestatin in patients with gastric cancer

SUMMARY OBJECTIVE: Gastric cancer ranks the third among the cancer-related deaths. It is diagnosed at advanced stage in many patients due to malignant proliferation and has a poor prognosis. Currently, no instrument or biomarker has been proven to diagnose the disease before the advanced stages. This study aimed to measure the serum levels of galanin and obestatin, which were examined in various studies including cancer studies, and to discuss their diagnostic value in gastric cancers. METHODS: In this study, 30 adult patients with gastric cancer and 30 healthy adults in the control group were examined prospectively. The demographic characteristics and serum levels of galanin and obestatin in the patient and control groups were recorded. RESULTS: The mean serum level of galanin in the patient and control groups was 19.73±5.04 and 35.59±10.94 pg/mL, respectively. The mean serum level of obestatin in the patient and control groups was 40.21±5.82 and 15.15±3.32 ng/mL, respectively. A significant difference was found between the groups (p<0.001). CONCLUSION: Serum levels of galanin were lower and serum levels of obestatin were higher in patients with gastric cancer compared to the healthy individuals. Serum levels of obestatin and galanin can be used as potential biomarkers in the diagnosis of gastric cancer.

Role of ghrelin and obestatin in the progression of nonalcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease (NAFLD) is a disease caused by multiple factors and can progress to liver cirrhosis and hepatocellular carcinoma. At present, the pathogenesis of NAFLD remains unclear and there are still no effective therapeutic drugs in clinical practice; therefore, it is particularly important to search for new therapeutic drugs that have few side effects and can effectively delay or reverse disease progression. Some studies have shown that related hormones produced by gastric tissue have a variety of effects in the regulation of energy homeostasis and obesity, and the expression level of inflammation-related genes in gastric fundus is consistent with the severity of liver disease; thus we have reason to believe that the stomach is one of the important participants in NAFLD. This article summarizes the role of ghrelin and obestatin produced by the stomach in the progression of NAFLD, which provides a new idea for the pathogenesis of NAFLD and a new direction for treatment.

Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

RESUMO OBJETIVO Nosso objetivo foi explorar os efeitos dos neuropeptídeos grelina, obestatina e peptídeo intestinal vasoativo (VIP) nas convulsões e concentrações plasmáticas de biomarcadores neuroinflamatórios, incluindo peptídeo relacionado ao gene da calcitonina (CGRP), substância-P (SP) e interleucina-1 beta (IL-1β) em convulsões induzidas por pentilenotetrazol em ratos. MÉTODOS Grelina (80 µg/kg), obestatina (1 µg/kg), VIP (25 ng/kg) ou solução salina foram administrados a ratos intraperitonealmente 30 minutos antes de injeções de pentilenotetrazol (PTZ, 50 mg/kg). Os estágios das crises epilépticas foram avaliados pela escala de Racine e as concentrações plasmáticas de CGRP, SP e IL-1β foram medidas usando Elisa. RESULTADOS Tanto a obestatina quanto o VIP encurtaram o tempo de início da crise tônico-clônica generalizada, respectivamente. Além disso, o VIP também encurtou o tempo de início do primeiro impulso mioclônico induzido por PTZ. Enquanto o PTZ aumentou as concentrações plasmáticas de CGRP, SP e IL-1β, a grelina reduziu os aumentos evocados por PTZ. Enquanto o VIP aumenta ainda mais os níveis de CGRP evocados por PTZ, diminui as concentrações de IL-1β. No entanto, a obestatina não alterou as concentrações de CGRP, SP e IL-1β. CONCLUSÃO Nossos resultados sugerem que a grelina tem anticonvulsivante, a obestatina tem proconvulsivante e o VIP tem ação dupla na epilepsia. Receptores desses neuropeptídeos podem ser alvos promissores para o tratamento da epilepsia.

Obestatin attenuates apoptosis induced by high glucose in INS 1 cells / 基础医学与临床

Objective To investigate the effect of obestatin on the apoptosis of rat pancreatic islet cell line INS1 induced by high glucose .Methods INS1 cells were cultured in different concentrations of glucose .The survival rate and proliferation of INS1 cells were detected by MTT method;Hoechst33258 nuclear staining was used to de-tect nuclear morphology.caspase-3 method was used to study the relationship between the protective effect of obestatin and the PI3K pathway;Finally,using real-time PCR detection of FOXO1 and SREBP1c, Bax, PDX-1 expression, to further clarify the protective effect of obestatin on cells.Results In high glucose condition,obesta-tin promoted the proliferation of INS1 cells at 100 nmol/L,and promoted the proliferation of INS 1 cells significantly ( P<0.01 , compared with the control group and high glucose group ) .Obestatin can reduce high glucose-induced apoptosis(P<0.01).The expressions of FOXO1,SREBP1c,Bax and PDX-1 decreased,while the expression of FOXO1,SREBP1c,Bax and PDX-1 increased in high glucose group .Conclusions OB can attenuate the injury of INS1 cells induced by high glucose in rats .

Combination of Obestatin and Bone Marrow Mesenchymal Stem Cells Prevents Aggravation of Endocrine Pancreatic Damage in Type II Diabetic Rats

One of the new promising therapies in treatment of diabetes mellitus is mesenchymal stem cells (MSCs) which have an interesting therapeutic potentiality based on their paracrine effect and transdifferentiation potentiality. Also obestatin improves the generation of functional β cells/islet-like cell clusters in vitro, suggesting implications for cell-based replacement therapy in diabetes. So the aim of this study was to evaluate the effect of combination of both MSCs and obestatin on an experimental model of type II diabetes mellitus (T2DM). Sixty male rats were divided into; group I (control group), group II (T2DM group) induced by administration of high fat diet (HFD) and injection of streptozotocin (STZ) in low dose, group III (T2DM treated with MSCs), group IV (T2DM treated with obestatin), group V (T2DM treated with MSCs and obestatin). Fasting blood glucose, C-peptide, insulin and lipid profile were measured. HOMA-IR and HOMA-β were calculated. Pancreatic expression of insulin, glucagon like peptide -1 (GLP-1) and pancreatic duodenal homeobox 1 (Pdx1) mRNA levels were measured. In addition pancreatic histological changes, insulin and Bax were analyzed by immunohistochemical examination of islets of Langerhans. Diabetic rats showed significant increase in HOMA-IR, serum glucose and lipid profile levels with significant decrease in insulin, HOMA-β, GLP-1 and Pdx1 levels. MSCs and obestatin caused significant improvement in all parameters with more significant improvement in combined therapy. The protective effects afforded by MSCs and obestatin may derive from improvement of the metabolic profile, antiapoptosis and by increase in pancreatic GLP-1and Pdx1 gene expression.

The study of ghrelin and obestatin system in patients with essential hypertension / 中国基层医药

Objective To measure the fasting plasma ghrelin and obestatin concentrations in essential hyper-tension (EH)patients with obesity,and to observe their relationship with blood pressure,obesity index,insulin resist-ance (IR),blood glucose and blood lipid.Methods 68 hypertensive obese patients,60 normotensive obese patients and 65 healthy controls were included in the study.The fasting plasma obestatin and ghrelin were measured using a radioimmunoassay method.The ghrelin/obestatin ratio was calculated.Results Hypertensive obese patients had lower plasma ghrelin and obestatin compared with normotensive obese patients (t =3.771,P <0.01;t =4.373,P <0.01) and controls (t =16.451,P <0.01;t =17.862,P <0.01).Normotensive obese patients had lower plasma ghrelin and obestatin compared with controls (t =13.121,P <0.01;t =13.686,P <0.01 ).Hypertensive obese patients had higher ghrelin/obestatin ratio than controls (t =7.720,P <0.01).The ghrelin/obestatin ratio in normotensive obese patients was higher than controls (t =4.587,P <0.01).In hypertensive obese group,the plasma ghrelin and obestatin were negatively associated with BMI (r =-0.882,P <0.01;r =-0.806,P <0.01),SBP (r =-0.787,P <0.01;r =-0.837,P <0.01),DBP (r =-0.769,P <0.01;r =-0.810,P <0.01),and the HOMA-IR (r =-0.800, P <0.01;r =-0.810,P <0.01).In normotensive obese group,ghrelin and obestatin were all negatively associated with BMI (r =-0.577,P <0.01;r =-0.372,P <0.01)and HOMA-IR (r =-0.866,P <0.01;r =-0.662,P <0.01).The ghrelin/obestatin ratio was positively associated with BMI (r =0.460,P <0.01)and HOMA-IR (r =0.420,P <0.01).Conclusion The peripheral blood ghrelin,obestatin and ghrelin/obestatin ratio were significantly correlated with EH,obesity and IR.No correlation was observed between ghrelin/obestatin system and blood lipid or blood glucose.

Circulating Ghrelin Levels and Obestatin/Ghrelin Ratio as a Marker of Activity in Ulcerative Colitis

BACKGROUND/AIMS: Ghrelin levels are known to increase in patients with ulcerative colitis (UC), but serum obestatin levels in UC patients are not well elucidated. The aim of this study was to examine the relationship between serum ghrelin and obestatin levels and disease activity in UC patients. METHODS: The serum ghrelin and obestatin levels were measured in 21 UC patients (12 with active disease and 9 in remission) using enzyme-linked immunosorbent assay. The relationship between the circulating levels of these 2 hormones and disease activity was analyzed. The colonic mucosal mRNA expression of ghrelin and obestatin was measured by quantitative reverse transcription polymerase chain reaction. RESULTS: The mean serum ghrelin values were significantly higher in patients with active disease than in patients with remission (1370.6+/-404.3 vs. 783.5+/-235.3 pg/mL, P=0.001). Colonic mucosal mRNA expression of ghrelin was also significantly higher in patients with active disease than in patients in remission (0.805+/-0.214 vs. 0.481+/-0.356, P=0.018). However, the mean serum obestatin levels and colonic mucosal mRNA expression of obestatin were not significantly different between both groups. The circulating obestatin/ghrelin ratio was significantly lower in patients with active UC than in patients in remission (0.32+/-0.08 vs. 0.58+/-0.20, P=0.001). CONCLUSIONS: The serum ghrelin levels and the obestatin/ghrelin ratio were related to the activity of UC, but serum obestatin was not related to activity of UC. The ghrelin levels and the obestatin/ghrelin ratio could serve as activity markers in patients with UC.

Strengthening control of blood glucose, blood pressure, and blood lipids in type 2 diabetes mellitus patients: Influence on obestatin level and relation with lipid metabolism / 第二军医大学学报

Objective To observe the influence of intensive control of blood glucose, blood pressure and blood lipid on fasting plasma obestatin level in type 2 diabetes mellitus (T2DM) patients and its correlation with lipid metabolism. Methods Seventy-two T2DM patients were assigned to four groups according to different treatments. Group A(n=25) received blood glucose (BG) and blood pressure(BP)controlling; group B(n=12) received BG, BP and blood lipid (BL) controlling; group C(n=20) received BG,BP, and BL controlling plus vitamin E administration; and group D(n=15) received BG,BP,BL controlling and compound Danshen dripping pill administration. Results Fasting obestatin level of group A was significantly lower than those in the other three groups (P<0.01). Fasting obestatin level was negatively correlated with body mass index (BMI), HbAlc, waist to hip ratio (WHR),total cholesterol(TC), low-density lipoprotein cholesterol (LDL-C), fasting insulin (FIN) and hemeostasis model assessment of insulin resistance (HOMA-IR) (P<0.05), and was positively correlated with high-density lipoprotein cholesterol (HDL-C) (P<0.05). After adjusting age, sex, BMI, WHR, blood glucose, and blood pressure, high level fasting obestatin was correlated with intensified control of blood lipid (P<0.01). Conclusion The fasting obestatin level is increased in T2DM patients receiving BL control compared with those do not receive, and obestatin level might be associated with lipid metabolism.

Yin and Yang: the Gastric X/A-like Cell as Possible Dual Regulator of Food Intake

Ingestion of food affects secretion of hormones from enteroendocrine cells located in the gastrointestinal mucosa. These hormones are involved in the regulation of various gastrointestinal functions including the control of food intake. One cell in the stomach, the X/A-like has received much attention over the past years due to the production of ghrelin. Until now, ghrelin is the only known orexigenic hormone that is peripherally produced and centrally acting to stimulate food intake. Subsequently, additional peptide products of this cell have been described including desacyl ghrelin, obestatin and nesfatin-1. Desacyl ghrelin seems to be involved in the regulation of food intake as well and could play a counter-balancing role of ghrelin's orexigenic effect. In contrast, the initially proposed anorexigenic action of obestatin did not hold true and therefore the involvement of this peptide in the regulation of feeding is questionable. Lastly, the identification of nesfatin-1 in the same cell in different vesicles than ghrelin extended the function of this cell type to the inhibition of feeding. Therefore, this X/A-like cell could play a unique role by encompassing yin and yang properties to mediate not only hunger but also satiety.

Effects of obestatin on amylase release of pancreatic acinar cells and lobules of rats / 中华胰腺病杂志

ObjectiveTo investigate the effects of different doses of obestatin on amylase secretion of pancreatic acinar and lobules of rats in vitro.MethodsPancreatic acinar cells of rats were separated in vitro and incubated with different doses of obestatin (0,0.1,1,10,30 nmol/L) for 1h,another group of pancreatic acinar ceils was incubated with obestatin for 30 min,then was incubated with 100 pmol/L CCK-8 for another 30 min.Pancreatic lobules,which containing intrapancreatic nerve terminals and islets,were prepared and were incubated with different concentrations of obestatin for 30 min at 37℃ with or without 75 mmol/L KCl.Amylase levels in the supernatants,acinar cells and pancreatic lobules were calculated as a percentage of total amylase content.ResultsObestatin (0,0.1,1,10,30 nmol/L) produced no significant change in basal amylase release of acinar cells [ (3.48 ± 1.44) ％,(3.70 ±- 1.39) ％,(3.36 ± 1.24) ％,(3.86 ± 1.41 ) ％,(4.54 ± 2.01 ) ％ ].CCK-8 significantly increased amylase release of acinar cells [ ( 13.84 ± 2.63 ) ％ vs (3.48 ± 1.44)％,P ＜0.05],but obestatin (0.1,1,10 nmol/L) has no effect on the amylase release inducedby CCK-8 [(14.55 ± 1.7)％,(13.79 ± 1.81)％,(14.39 ± 1.12)％].Obestatin (0.1,1,10,30 nmol/L) did not affect the amylase release of pancreatic lobuole.KCl significantly increased anylase release,which was ( 1.84 ± 0.29 ) folds higher than that of control group ( P ＜ 0.05 ),but obestatin has no effect on the amylase release induced by KCl,which were (2.01 ± 0.30 ),( 1.89 ± 0.41 ),( 1.74 ± 0.14 ),( 1.88± 0.33) folds higher than those of control group.ConclusionsExogenous obestatin has no effects on pancreatic exocrine of acinar cells and lobules of rats in vitro and cannot block or assist the increased amylase release induced by CCK-8 or KCl.

Obestatin inhibits proliferation and differentiation of 3T3-L1 preadipocytes / 第二军医大学学报

Objective: To investigate the inhibitory effects of obestatin on proliferation and differentiation of 3T3-L1 preadipocytes. Methods: Obestatin (10-8 mmol/L, 10-9 mmul/L, 10-10 mmol/L, 10-11 mmol/L, and 10-12 mmol/L) and ghrelin (10-10 mmol/L) were used to treat 3T3-L1 preadipocytes. Cell proliferation was assessed by MTT assay and the results were compared with that of blank control group. The differentiation of 3T3-L1 preadipocytes (from day 1 to day 10) was interfered with obestatin or ghrelin (both at 10-10 mmol/L). Intracellular fat accumulation in differentiated adipocytes was determined by oil red O staining and the expression of PPAR-γ2 mRNA was detected by RT-PCR; the results were compared with that of control group (induced with routine inducer). Results: Compared with the blank control group, obestatin-treated groups (various concentrations of obestatin) had significantly less cells(P<0.05). Oil red O staining revealed that, compared with control group, the formation of lipid droplets was significantly decreased after 10 days' of treatment with 10-10 mmol/L obestatin (P<0.05). The expression of PPARγ2 gene increased with the progress of 3T3-L1 preadipocytes differentiation. PPAR-γ2 mRNA level in mature adipocytes of obestatin group was significantly lower than that in the cells of control group. The effect of ghrelin was contrary to that of obestatin. Conclusion: Obestatin can inhibit the proliferation and differentiation of 3T3-L1 preadipocyes.

Fasting plasma obestatin levels in patients with different glucose tolerance and its association with lipid metabolism / 中华老年医学杂志

Objective To investigate whether fasting obestatin level is different in patients with impaired glucose tolerance or type 2 diabetes, and to explore the association between obestatin and lipid metabolism. Methods Eighty-four subjects without known diabetes were divided into three groups: normal glucose tolerance(NGT), impaired glucose tolerance (IGT) and type 2 diabetes (DM) Plasma obestatin levels were measured with a radioimmunoassay. The relationship between fasting obestatin levels and metabolic parameters was also analyzed. Results Fasting obestatin levels were lower in DM group [(2.82±0.78)ng/ml] and IGT group [(3.25±0.29)ng/ml] than in NGT group[(3.55±0.57) ng/ml, P＜0.01]. Triglycerides and low density lipoprotein cholesterol levels gradually increased among the three groups (P＜0.05). Multiple linear regression analysis revealed fasting obestatin level was independently associated with waist-to-hip ratio, triglyeride and low density lipoprotein cholesterol. The regression equation was obestatin=6.953-3.412×W/H-0.175×TG-0.123×LDL-C. Conclusions The decreased obestatin may be associated with IGR and T2DM, and obestatin level may be associated with lipid metabolism.

Reduction of plasma obestatin levels in patients with impaired glucose regulation and type 2 diabetes / 中华内分泌代谢杂志

Plasma obestatin level was determined in patients with impaired glucose regulation and type 2 diabetes mellitus.The plasma obestatin levels in patients of both groups were significantly decreased as compared with that in controls.Plasma obestatin level was negatively correlated with body mass index,HbA_(1C),waist-to-hip ratio,plasma insulin and HOMA-IR.Obestatin level seems to be related with metabolic disorder.