生产素(Ghrelin)对胃肠道的保护和治疗作用

生长素（Ghrelin）最初是由日本学者Kojima等[1]从人和鼠的胃中分离出来的且是一种主要来源胃的脑肠肽[2]。Ghrelin是生长激素促分泌素受体1a（growth hormone secretagogue receptor 1a,GHS-R1a）的惟一的一个内源性配体,与垂体前叶作用后能够强烈的促进生长激素的释放,并呈剂量依赖性[1]。Ghrelin除了具有刺激生长激素释放作用外,还能够促进食物吸收和胃的排空以及调节能量消耗等多种生理功能,并且对胃肠道具有保护和促进愈合的作用。本文主要综述了Ghrelin对动物和人类胃肠道的保护和治疗作用最新研究进展。

An overview on antidiabetic medicinal plants having insulin mimetic property

Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8%of the world's population and is anticipated to cross 5.4%by the year 2025.Since long back herbal medicines have been the highly esteemed source of medicine therefore,they have become a growing part of modern,high-tech medicine.In view of the above aspects the present review provides profiles of plants(65 species) with hypoglycaemic properties,available through literature source from various database with proper categorization according to the parts used,mode of reduction in blood glucose(insulinomimetic or insulin secretagugues activity) and active phyloconsliluents having insulin mimetics activity.From the review it was suggested that,plant showing hypoglycemic potential mainly belongs to the family Leguminoseae,Lamiaceae,Liliaceae,Cucurbitaceae, Asteraceae,Moraceae,Rosaceae and Araliaceae.The most active plants are Allium sativum. Gymnema sylvestre,Citrullus colocynthis,Trigonella foenum greacum,Momordica charantia and Ficuts bengalensis.The review describes some new bioactive drugs and isolated compounds from plants such as roseoside,epigallocatechin gallate,beta-pyrazol-1-ylalanine,cinchonain Ib,leucocyandin 3-O-beta-d-galactosyl cellobioside,leucopelargonidin-3- O-alpha-L rhamuoside,glycyrrhetinic acid,dehydrotrametenolic acid,strictinin,isostrictinin,pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents.Thus,from the review majorly,the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols,flavonoida, terpenoids,coumarins and other constituents which show reduction in blood glucose levels.The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.

GHRP-6 Induces CREB Phosphorylation and Growth Hormone Secretion via a Protein Kinase Cσ-dependent Pathway in GH3 Cells

This study examined the effect of GHRP-6, a known GHSs receptor agonist, on the phosphorylation of cAMP-responsive element-binding protein （CREB） and the tmderly mechanism. GH3 cells were cultured and subjected to different treatments as follows： GHRP-6, GHRP-6 plus GHRH, phorbol ester （PMA）, an activator of PKC, alone or in combination with GHRP-6, G66983, a general inhibitor of PKCs, in the presence or absence of GHRP-6, rottlerin, an inhibitor of PKCs, alone or plus GHRP-6. The cells were transiently transfected with PKCσ-specific siRNA and then treated with GHRP-6. GH level was measured by enzyme-linked immunosorbent assay （ELISA）. The expression of phosphor-CREB, PKCσ, PKC0 and phosphor-PKCo was determined by Western blotting. The results showed that GHRP-6 stimulated GH secretion in both time- and dose-dependent manners and enhanced the effect of GHRH on GH secretion. GHRP-6 was also found to induce CREB phosphorylation. Moreover, GH secretion was enhanced by the PKC activator PMA and reduced by the PKC inhibitors （G66983, rottlerin） and knockdown of PKCσ. PKCσ could be activated by GHRP-6. It is concluded that PKC, especialiy PKCσ, mediates CREB phosphorylation and GHRP-6-induced GH secretion.

Recent standardization of treatment strategy for pancreatic neuroendocrine tumors

Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.

<i>In Vivo</i>and <i>in Vitro</i>Evaluation of Anti Diabetic and Insulin Secretagogue Activities of <i>Capparis zeylanica</i>

Since ancient times, traditional medicines have been in the usage for the treatment of Diabetes mellitus. An edible fruit from traditional medicinal plant Capparis zeylanica (CZ) was studied for its anti diabetic, insulin secretagogue activities and mechanisms involved in it. In Streptozotocin induced diabetes rats, oral administration of Capparis zeylanica methanolic extract (CZME) (200 mg/kg body weight) for 28 days showed a significant reduction in blood glucose levels by 35.53% and enhanced circulating insulin levels by 81.82% than the diabetic control rats. The insulin secretagogue activity mechanisms of the extract were evaluated by using mouse insulinoma beta cell line (MIN6-β). The extract stimulated insulin release in dependent manner of glucose concentration (3 - 16.7 mM) and extract dose (5 - 500 μg/mL). The insulin releasing effect of the extract was significantly enhanced by 3-isobutyl-1-methyl xanthine, glibenclamide, elevated extracellular calcium and K+ depolarized media. This insulin release was significantly reduced in calcium blocking conditions (by nifedipine and EGTA), in the presence of potassium channel opener (diazoxide). Hence, anti diabetic activity of CZME might be a result of its stimulatory effect on insulin release from pancreatic beta cells via KATP channel dependent and independent ways. These results indicate that CZ fruits have the potential to use in diabetes therapy.

Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro

Background Diabetic 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. Methods A 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 μg/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 μg/kg） was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 （0.01-10 μmol/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）. Results We established a guinea pig model of delayed gastric emptying. Ghrelin （20, 50, or 100 μg/kg） and GHRP-6 （20, 50, or 100 μg/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 μg/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. Conclusions Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.

Effect of electroacupuncture on expression of ghrelin and mRNA expression of its receptor in functional dyspepsia rats

Objective To explore the effect of electroacupuncture(EA)on the expression of ghrelin and mRNA expression of its receptor in functional dyspepsia(FD)rats.Methods Totally 80 rats were divided into the normal group,the model group,the drug therapy group,and the EA group according to random digit table,20 in each group.FD model was duplicated by clipping tail modeling.Drug containing cisapride[2 m L/100 g,