2.Combination of Obestatin and Bone Marrow Mesenchymal Stem Cells Prevents Aggravation of Endocrine Pancreatic Damage in Type II Diabetic Rats.
Noha I HUSSIEN ; Nesrine EBRAHIM ; Ola M MOHAMMED ; Dina SABRY
International Journal of Stem Cells 2017;10(2):129-143
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.
Animals
;
Blood Glucose
;
Bone Marrow*
;
C-Peptide
;
Diabetes Mellitus
;
Diet, High-Fat
;
Fasting
;
Gene Expression
;
Genes, Homeobox
;
Ghrelin*
;
Glucagon
;
Glucagon-Like Peptide 1
;
Humans
;
In Vitro Techniques
;
Insulin
;
Islets of Langerhans
;
Male
;
Mesenchymal Stromal Cells*
;
Metabolome
;
Models, Theoretical
;
Rats*
;
RNA, Messenger
;
Streptozocin
5.Effects of plasma ghrelin, obestatin, and ghrelin/obestatin ratio on blood pressure circadian rhythms in patients with obstructive sleep apnea syndrome.
Weiying LIU ; Hongmei YUE ; Jiabin ZHANG ; Jiayuan PU ; Qin YU
Chinese Medical Journal 2014;127(5):850-855
BACKGROUNDObstructive sleep apnea syndrome (OSAS) is strongly associated with obesity and with cardiovascular disease. Ghrelin and obestatin are two peptides from the same source but have opposite roles. Both of them can affect feeding and regulate vascular tune. The aim of this study was to investigate the relationship between plasma ghrelin, obestatin, the ratio of ghrelin and obestatin (G/O) and sleep parameters and blood pressure circadian rhythms in patients with OSAS.
METHODSThis study enrolled 95 newly diagnosed over-weight OSAS patients (OSAS group), 30 body mass index (BMI)-match non-OSAS adults (over-weight group) and 30 non-OSAS normal weight adults (control group). Polysomnography (PSG) was performed in the OSAS group and over-weight group. Blood pressure of all subjects was monitored by means of 24-hour ambulatory blood pressure monitoring. The concentration of plasma ghrelin and obestatin was detected by enzyme-linked immunosorbent assay (ELISA).
RESULTSPlasma ghrelin levels in the OSAS group and over-weight group were significantly lower than that of the control group (P < 0.05). Plasma obestatin levels were lower in the over-weight group and OSAS group, but there was no significant difference among the three groups. The blood pressure in OSAS patients was higher, and there was a significant difference in all blood pressure parameters compared to the control group, and in the daytime average diastolic blood pressure (DBP), nocturnal average systolic blood pressure (SBP) and DBP, DBP variability values as compared to over-weight subjects. Furthermore, there were significantly more non-dipper patterns of blood pressure (including hypertension and normotension) in the OSAS group than in the other two groups (P < 0.01). Correlation analysis showed that ghrelin levels had a significant correlation with BMI and nocturnal average DBP but not with PSG parameters. In contrast, the G/O ratio had a negative correlation with apnea-hypopnea index (AHI) (P < 0.05), as well as a strong positive correlation with the blood pressure variability values (P < 0.01). In multivariate analyses, AHI (P < 0.05) and G/O (P < 0.05) were independently related to SBP variability changes, while AHI (P < 0.05), G/O (P < 0.01) and BMI (P < 0.05) were independently related to DBP variability changes.
CONCLUSIONSOur data show plasma ghrelin and obestatin levels were related to obesity in OSAS. Sleep apnea in OSAS patients could have led to an imbalance in G/O in the basis of obesity. Moreover, the imbalance may promote nighttime blood pressure elevation and affect blood pressure circadian disorder.
Adolescent ; Adult ; Aged ; Blood Pressure ; physiology ; Circadian Rhythm ; physiology ; Enzyme-Linked Immunosorbent Assay ; Female ; Ghrelin ; blood ; Humans ; Male ; Middle Aged ; Obesity ; blood ; physiopathology ; Pancreatic Neoplasms ; blood ; physiopathology ; Prognosis ; Repressor Proteins ; metabolism ; Sleep Apnea, Obstructive ; blood ; physiopathology ; Young Adult
6.Impacts on the appetite regulating factors of infantile anorexia treated with acupuncture at Sifeng (EX-UE 10).
Mei-Yuan FU ; Guo-Hua HU ; Xiang-Feng ZHOU ; Bao-Xiang HE ; Li-Xing HE ; Bing-Lun HUANG ; Su-Hua GAO
Chinese Acupuncture & Moxibustion 2013;33(2):117-120
OBJECTIVETo explore the dynamic change and clinical efficacy of acupuncture at Sifeng (EX-UE 10) on appetite regulating factors in the serum of infantile anorexia.
METHODSEighty cases, in compliance with the diagnostic criteria, aged from 3 to 6 years were randomized into an acupuncture group and a medication group, 40 cases in each one. Additionally, a healthy control group (30 cases) was set up. In the acupuncture group, the pricking method was adopted at Sifeng (EX-UE 10) with the three-edged needle. A few light yellow, transparent viscous liquid or blood was squeezed out after pricking. The treatment was given once a week, for 4 weeks totally. In the medication group, erkangning syrup was administered, 3 times a day, for 4 weeks totally. The ghrelin, leptin and neuropeptide Y (NPY), and the clinical efficacy were observed before and after treatment in each group.
RESULTSThe levels of ghrelin and NPY before treatment in acupuncture group and the medication group were lower apparently than those in the healthy control group (all P < 0.01), but the level of leptin was higher appa-rently than that in the healthy control group (P < 0.01). After treatment, the levels of ghrelin and NPY were higher apparently than those before treatment in the acupuncture group (both P < 0.01), and the level of leptin was lower apparently than that before treatment (P < 0.01). All of the above indices in the acupuncture group were improved obviously after treatment as compared with those in the medication group (all P < 0.01). The remarkable and effective rate were 82.5% (33/40) and 32.5% (13/40) and the total effective rate were 95.0% (38/40) and 45.0% (18/40) in the acupuncture group and medication group separately, the results in the acupuncture group were superior to the medication group (both P < 0.01).
CONCLUSIONAcupuncture at Sifeng (EX-UE 10) effectively promotes the secretion of ghrelin and NPY and inhibit leptin. It effectively promotes appetite for the children and the efficacy is superior to erkangning syrup.
Acupuncture Points ; Acupuncture Therapy ; Anorexia ; blood ; physiopathology ; therapy ; Appetite ; Child, Preschool ; Female ; Ghrelin ; blood ; Humans ; Leptin ; blood ; Male ; Neuropeptide Y ; blood ; Treatment Outcome
7.Circulating ghrelin was negatively correlated with pulmonary arterial pressure in atrial septal defect patients.
Zhao-feng LI ; Da-xin ZHOU ; Wen-zhi PAN ; Lei ZHANG ; Jun-bo GE
Chinese Medical Journal 2013;126(20):3936-3939
BACKGROUNDGhrelin was found to attenuate the magnitude of pulmonary arterial hypertension and pulmonary vascular remodeling in rats. The objective of this study was to explore the fasting plasma ghrelin level and the relationships between ghrelin and pulmonary arterial pressure (PAP) in atrial septal defect (ASD) patients with pulmonary arterial hypertension (PAH).
METHODSFasting plasma ghrelin, obestatin, and insulin levels were measured by enzyme linked immunosorbent assay (ELISA) method in ASD patients with or without PAH according to the manufacturer's instructions. Insulin resistance was calculated by the homeostasis model of assessment for insulin resistance (HOMA-IR) approach, calculated as fasting insulin (microunits/ml)× fasting blood glucose (mmol/L)/22.5. Comparisons between the parameters of patients with PAH and those of patients with normal PAP were performed with an unpaired Student's t test. The relationships between ghrelin and various clinical parameters were examined by bivariate correlations and multiple regression analysis.
RESULTSWe found that the fasting plasma ghrelin level and the ratio of ghrelin to obestatin were significantly lower in the PAH group compared with the control group ((582.4±12.8) pg/ml vs. (1045.2±95.5) pg/ml, P < 0.05 and 30.5±4.9 vs. 70.0±9.7, P < 0.01). The fasting plasma obestatin level was higher in the PAH group compared with the control group, but the difference between them was not significant ((23.2±3.1) pg/ml vs. (16.3±1.6) pg/ml, P > 0.05). In a multiple regression model analysis, only mean PAP was an independent predictor of ghrelin and the ratio of ghrelin to obestatin (standardized coefficient = -0.737, P < 0.001 and standardized coefficient = -0.588, P = 0.006, respectively).
CONCLUSIONGhrelin is negatively correlated with mean PAP and this suggests that circulating ghrelin might predict the severity of pulmonary hypertension in ASD patients with PAH.
Adolescent ; Adult ; Enzyme-Linked Immunosorbent Assay ; Familial Primary Pulmonary Hypertension ; Fasting ; blood ; Female ; Ghrelin ; blood ; Heart Septal Defects, Atrial ; blood ; physiopathology ; Humans ; Hypertension, Pulmonary ; blood ; physiopathology ; Insulin ; blood ; Male ; Middle Aged ; Young Adult
8.Effects of nasal continuous positive airway pressure treatment on insulin resistance and ghrelin levels in non-diabetic apnoeic patients with coronary heart disease.
Dan YANG ; Zhi-Hong LIU ; Qing ZHAO ; Qin LUO
Chinese Medical Journal 2013;126(17):3316-3320
BACKGROUNDObesity is a common risk factor for several diseases. Obesity related hormone and increased insulin resistance (IR) may contribute to the effects of obstructive sleep apnoea on cardiovascular consequences. We investigated ghrelin and IR in non-diabetic apnoeic patients with stable coronary heart disease and assessed the effects of continuous positive airway pressure (CPAP).
METHODSPlasma ghrelin, glucose and insulin were measured in 22 patients with CPAP and 22 matched controls without CPAP at baseline and three months. Indexes including homeostasis model assessment IR (HOMA IR), HOMA S and HOMA β were calculated for the assessment of IR, insulin sensitivity and pancreatic β cell function.
RESULTSAt three months follow-up, plasma ghrelin levels and HOMA IR in CPAP group were significantly decreased (P=0.002 and 0.046, respectively) while those in control group increased significantly (P=0.012 and 0.009, respectively). Significant moderate correlations were found between ghrelin vs. HOMA IR and ghrelin vs. HOMA S after CPAP, however, for those without CPAP, no significant associations were observed.
CONCLUSIONSShort-term effective continuous positive airway pressure had a significant effect on lowering plasma ghrelin levels and IR, but not body fat. Further large scale and longer term studies are warranted to corroborate these findings.
Blood Glucose ; Case-Control Studies ; Continuous Positive Airway Pressure ; methods ; Coronary Artery Disease ; blood ; Female ; Ghrelin ; blood ; Humans ; Insulin ; blood ; Insulin Resistance ; physiology ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; therapy
9.Establishment of sleeve gastrectomy model in diet-induced obese Sprague-Dawley rats.
Guan-jun MA ; Wei ZHANG ; Xiang-min ZHENG ; Ming QIU
Chinese Journal of Gastrointestinal Surgery 2012;15(1):43-46
OBJECTIVETo establish sleeve gastrectomy(SG) rats model of obese type 2 diabetes mellitus(T2DM) for the research of hypoglycemic mechanism.
METHODSNine male Sprague-Dawley (6-week-old) rats were fed with high-sucrose and high-fat diet for 4 weeks, developing diet-induced obesity (DIO) rats model. The rats were then randomly divided into two groups. Six rats of them underwent sleeve gastrectomy(SG) as the sleeve gastrectomy group[SGG, body weight (471.8±17.9) g] and the other three rats underwent a laparotomy and stomach manipulation as the sham operative group[SOG, body weight (467.0±8.4) g]. The body weight, caloric intake and peripheral blood concentration of total ghrelin of rats were recorded after operation.
RESULTSThe weight of all the rats declined progressively after operation. The weight of the rats in SOG began to rise on the 5th postoperative day(POD) and regain their preoperative levels on the average 22nd POD. However, the weight of the rats in SGG began to rise slowly from the 9th POD, but was still lower than that of SOG[(487.4±10.1) g] and preoperative levels[(471.8±17.9) g] on the 28th POD[(420.1±18.6) g](P=0.001). Average caloric intake of rats in SGG was significantly lower than that of SOG after operation, but there was no significant difference between the two groups(P=0.121). The ghrelin level of SGG showed a continuous decreasing trend after intervention, decreased by 17.4% compared with the preoperative level (1595.1±14.4 ng/L) on the 28th POD[(1316.8±14.8) ng/L]. The ghrelin level of SOG did not change obviously before and after operation and both groups differ statistically(P=0.000).
CONCLUSIONSA SG rat model is successfully established. This model can be used for the further study of mechanism analysis of T2DM resolution after surgery.
Animals ; Diabetes Mellitus, Type 2 ; pathology ; Disease Models, Animal ; Gastrectomy ; methods ; Ghrelin ; blood ; Male ; Obesity ; blood ; surgery ; Rats ; Rats, Sprague-Dawley
10.Effect of in ovo ghrelin administration on serum malondialdehyde level in newly-hatched chickens.
Alireza LOTFI ; Habib Aghdam SHAHRYAR ; Yahya EBRAHIMNEZHAD ; Jalal SHAYEGH
Asian Pacific Journal of Tropical Biomedicine 2012;2(1):47-49
OBJECTIVETo investigate effects of in ovo ghrelin administration on serum malondialdehyde (MDA) level in newly-hatched chickens.
METHODSFertilized eggs were divided into 7 groups: group T1 as control (without injection), group T2 (in ovo injected with 50 ng/egg ghrelin on day 5), group T3 (in ovo injected with 100 ng/egg ghrelin on day 5), group T4 (in ovo injected with 50 ng/egg ghrelin on day 10), group T5 (in ovo injected with 100 ng/egg ghrelin on day 10), group T6 (in ovo injected with solvent: 1% acetic acid, without ghrelin on day 5) and group T7 (in ovo injected with solvent without ghrelin on day 10). After hatching, serum MDA concentrations were determined.
RESULTSGhrelin administrated groups (T2, T3, T4 and T5) had lower serum MDA level in comparison with control group (T1) or solvent injected groups (T6 and T7). T2 and T3 (ghrelin injection on day 5) had significantly lower MDA concentrations (4.10 and 4.60 nmol/mL, respectively) in comparison with other groups. In T4 and T5, MDA levels were lower than T1, T6 and T7 (non-ghrelin administrated groups) (9.53 and 9.50 in comparison with 10.73, 10.03 and 10.13 nmol/mL) and were higher than T2 and T3.
CONCLUSIONSIt can be concluded that in ovo administration of ghrelin can have anti-oxidative protection and reduce serum MDA level. Ghrelin administration on day 5 of incubation is more efficient.
Animals ; Antioxidants ; administration & dosage ; Chickens ; Ghrelin ; administration & dosage ; Malondialdehyde ; blood ; Serum ; chemistry

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