No abstract available.
Anti-Ulcer Agents/*therapeutic use ; Chromogranin A/*blood ; Combined Modality Therapy ; Gastrins/*blood ; Ghrelin/*blood ; Histamine H2 Antagonists/*therapeutic use ; Humans ; Proton Pump Inhibitors/*therapeutic use

Type 2 diabetes is a high-profile global public health problem, particularly in Asia. The young age of onset, low body mass index, and early appearance of pancreatic islet dysfunction are characteristics of Asian patients with T2DM. Metabolic surgery has become the standard treatment for T2DM patients and can significantly improve T2DM through a variety of mechanisms including modulation of energy homeostasis and reduction of body fat mass. Indeed, restoration of islet function also plays an integral role in the remission of T2DM. After metabolic surgery, islet function in Asian T2DM patients has improved significantly, with proven short-term and long-term effects. In addition, islet function is an important criterion and reference for patient selection prior to metabolic surgery. The mechanism of islet function improvement after metabolic surgery is not clear, but postoperative anatomical changes in the gastrointestinal tract leading to a number of hormonal changes seem to be the potential cause, including glucagon-like peptide-1, gastric inhibitory polypeptide, peptide YY, ghrelin, and cholecystokinin. The authors analyzed the current retrospective and prospective studies on the effect of metabolic surgery on the islet function of Asian T2DM patients with a low BMI and its mechanism, summarized the clinical evidence that metabolic surgery improved islet function in Asian T2DM patients with a low BMI, and discussed its underlying mechanism. It is of great significance for realizing personalized and precise treatment of metabolic surgery and further improving its clinical benefits.
Bariatric Surgery ; Body Mass Index ; Cholecystokinin/therapeutic use* ; Diabetes Mellitus, Type 2/surgery* ; Gastric Inhibitory Polypeptide/therapeutic use* ; Ghrelin/therapeutic use* ; Glucagon-Like Peptide 1/therapeutic use* ; Humans ; Peptide YY/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Treatment Outcome

BACKGROUNDDiabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 (GHRP-6), increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.

METHODSA diabetic guinea pig model was produced by intraperitoneal (i.p.) injection of streptozotocin (STZ, 280 mg/kg). Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 (10 - 100 microg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor (GHS-R) antagonist, D-Lys(3)-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 (100 microg/kg) was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 (0.01 - 10 micromol/L) on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction (RT-PCR).

RESULTSWe established a guinea pig model of delayed gastric emptying. Ghrelin (20, 50, or 100 microg/kg) and GHRP-6 (20, 50, or 100 microg/kg) accelerated gastric emptying in diabetic guinea pigs with gastroparesis (n = 6, P < 0.05). In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 (100 microg/kg) failed to accelerate gastric emptying (n = 6, P < 0.05). D-Lys(3)-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist (n = 6, P < 0.05). Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs (n = 6, P < 0.05). RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.

CONCLUSIONSGhrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.

Animals ; Diabetes Mellitus, Experimental ; complications ; Female ; Gastric Emptying ; drug effects ; Gastroparesis ; drug therapy ; physiopathology ; Ghrelin ; therapeutic use ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction ; drug effects ; Oligopeptides ; therapeutic use ; Receptors, Ghrelin ; analysis ; Streptozocin

OBJECTIVE: To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms. METHODS: Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD). RESULTS: MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD. CONCLUSIONS MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.
Rats ; Mice ; Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Ghrelin/metabolism* ; Antidepressive Agents/therapeutic use* ; Hippocampus ; Stress, Psychological ; Mammals/metabolism*

Gastrointestinal (GI) motility has a crucial role in the food consumption, digestion and absorption, and also controls the appetite and satiety. In obese patients, various alterations of GI motility have been investigated. The prevalence of GERD and esophageal motor disorders in obese patients are higher than those of general population. Gastric emptying of solid food is generally accelerated and fasting gastric volume especially in distal stomach is larger in obese patients without change in accommodation. Contractile activity of small intestine in fasting period is more prominent, but orocecal transit is delayed. Autonomic dysfunction is frequently demonstrated in obese patients. These findings correspond with increased appetite and delayed satiety in obese patients, but causes or results have not been confirmed. Therapeutic interventions of these altered GI motility have been developed using botulinum toxin, gastric electrical stimulation in obese patients. Novel agents targeted for GI hormone modulation (such as ghrelin and leptin) need to be developed in the near future.
Botulinum Toxins/therapeutic use ; Colon/*physiopathology ; Eating ; Electric Stimulation Therapy ; Esophageal Motility Disorders/etiology/*physiopathology/therapy ; *Gastrointestinal Motility ; Ghrelin/therapeutic use ; Humans ; Intestine, Small/*physiopathology ; Leptin/therapeutic use ; Obesity/*complications ; Satiety Response ; Stomach/innervation/*physiopathology

BACKGROUND/AIMS: Long-term use of proton pump inhibitor (PPI) induces hypergastrinemia, which results from the suppression of gastric acid secretion. Hypergastrinemia causes enterochromaffin-like (ECL) cell hyperplasia, which is a predisposing factor of carcinoid tumor of stomach. The aim of this study was to identify the effect of long-term gastric acid suppression on the gastric peptides levels, such as gastrin, chromogranin A, or ghrelin. METHODS: Control group included patients who had no medication over six months. Both H2RA (H2 receptor antagonist) and PPI groups had medication at least for six months. Fasting blood was taken from each patient to assay serum gastrin, chromogranin A, and ghrelin by RIA and ELISA techniques. RESULTS: The patients with the above reference range of serum gastrin and chromogranin A were more commonly found in PPI group compared to control and H2RA group. However, serum ghrelin level was within the reference range in all the patients regardless of groups. There was no difference in the ratio of serum gastrin/chromogranin A among three groups. Both average serum levels of gastrin and chromogranin A were significantly elevated in PPI group compared to control and H2RA group. There was a significant correlation between the level of serum gastrin and chromogranin A. CONCLUSIONS: Long-term administration of H2RA does not affect the serum gastrin and chromogranin A level. However, long-term administration of PPI increases serum gastrin and chromogranin A. Ghrelin may influence gastric acid secretion in other pathway than ECL cell-mediated pathway such as gastrin or chromogranin A.
Adult ; Aged ; Anti-Ulcer Agents/*therapeutic use ; Chromogranin A/*blood ; Female ; Gastrins/*blood ; Ghrelin/*blood ; Histamine H2 Antagonists/*therapeutic use ; Humans ; Male ; Middle Aged ; Proton Pump Inhibitors/*therapeutic use ; Time Factors

It has been suggested that Helicobacter pylori eradication may influence production of some peptides in the stomach, which can affect appetite. This hypothesis is controversial. To verify the hypothesis, we conducted this randomized controlled trial using H. pylori infected subjects without any gastrointestinal symptoms. The treatment group received triple H. pylori eradication therapy for 7 days and the control group received no medication. We measured ghrelin, obestatin and the tumor necrosis factor-alpha (TNF-alpha) mRNA levels in endoscopic biopsy specimens and the changes from baseline to follow-up. The plasma active n-octanoyl ghrelin and obestatin levels were measured in both groups. The ghrelin/obestatin ratios in plasma and gastric mRNA expression were calculated at baseline and follow-up. Ghrelin mRNA expression in the fundic mucosa after H. pylori eradication increased significantly compared to the control group (4.47+/-2.14 vs. 1.79+/-0.96, P=0.009), independent of inflammatory changes. However, obestatin mRNA expression decreased in the antral mucosa (-0.57+/-1.06 vs. 0.41+/-0.72, P=0.028). The treatment group showed a marginal increase (P=0.060) in plasma ghrelin/obestatin ratio. The TNF-alpha mRNA expression also decreased significantly with treatment. This randomized controlled trial demonstrates that H. pylori eradication increases ghrelin mRNA expression, independent of inflammatory cell changes.
Adult ; Aged ; Anti-Bacterial Agents/therapeutic use ; Female ; Gastric Mucosa/*metabolism/microbiology ; Gastroscopy ; Ghrelin/blood/genetics/*metabolism ; Helicobacter Infections/drug therapy/genetics/*metabolism ; *Helicobacter pylori ; Humans ; Male ; RNA, Messenger/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism

We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-alpha, IFN-gamma, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-alpha, IFN-gamma, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 +/- 19.5 vs 80.9 +/- 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.
Adiponectin/analysis ; Aged ; Antineoplastic Agents/therapeutic use ; Cachexia/*physiopathology ; Colorectal Neoplasms/drug therapy/*metabolism/mortality ; Cytokines/*analysis ; Female ; Follow-Up Studies ; Ghrelin/analysis ; Humans ; Interferon-gamma/analysis/physiology ; Interleukin-6/analysis ; Leptin/analysis ; Lung Neoplasms/drug therapy/*metabolism/mortality ; Male ; Middle Aged ; Peptide Hormones/*analysis ; Prognosis ; Prospective Studies ; Survival Rate ; Tumor Necrosis Factor-alpha/analysis ; Weight Gain ; Weight Loss