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.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
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.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
9.Diltiazem enhances food intake and gastrointestinal function in rats.
Li-Na WANG ; Sheng-Li LI ; Chuang-Hong LI ; Chen-Xu ZHANG ; Hui YUAN ; Xin-Ping LI
Acta Physiologica Sinica 2012;64(2):187-192
The present study was to investigate the effects of diltiazem, a ghrelin receptor agonist, on food intake and gastrointestinal functions in rats. Rats were intragastrically administered with diltiazem solution (daily 16 mg/kg, 30 mg/kg or 80 mg/kg, 30 d), and the rats with saline as control. To detect the effects of diltiazem on food intake and body weight, the average daily food intake and body weight were recorded, and the serum metabolic hormones of plasma growth hormone (GH) and neuropeptide Y (NPY) were tested by radioimmunoassay. By means of the spectrophotometer and the modified Mett's method, the effects of diltiazem on rat's gastrointestinal function and pepsin activity were tested, respectively. In addition, the gastric juice's acidity of rats was detected by titration and the secretion amount was calculated. The results showed that the food intake and body weight were maximally promoted by diltiazem at the dose of 30 mg/kg daily (30 d). The average daily food intake and body weight were significantly increased, and the serum concentrations of GH and NPY were also remarkably increased in diltiazem-treated groups compared with those in control group. The results also showed that the gastric emptying rate, gastric acid secretion and the activity of pepsin were significantly increased in diltiazem-treated group compared with those in control group. These results suggest that diltiazem induces enhancement of eating, in the same time, it can also stimulate the gastrointestinal function and regulate growth of rat.
Animals
;
Body Weight
;
drug effects
;
Diltiazem
;
pharmacology
;
Eating
;
drug effects
;
Female
;
Gastric Emptying
;
drug effects
;
Gastrointestinal Motility
;
drug effects
;
Gastrointestinal Tract
;
physiology
;
Growth Hormone
;
blood
;
Neuropeptide Y
;
blood
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Ghrelin
;
agonists
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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