These were still significantly less than CCK-stimulated release. release paralleled that of amylin. Conclusions The cultured D-cell model provides a Syringic acid means of studying amylin release. Amylin secretion is usually stimulated by receptor-dependent and -impartial activation of Ca2+/protein kinase C and adenylate cyclase pathways. Inhibition entails activation of muscarinic receptors and auto-regulation by somatostatin. Background Amylin (islet amyloid polypeptide) is usually a 37-amino acid peptide predominantly expressed in the pancreatic Islets of Langerhans [1,2]. Amylin has also been localised throughout the gastrointestinal tract [3] and in the brain [4]. Much recent work has focused on the physiology of pancreatic amylin; the peptide appears to be co-stored and co-secreted with insulin in pancreatic B-cells [5,6], a smaller proportion is usually co-localised with somatostatin in pancreatic D-cells [7]. Amylin is usually believed to function as a hormone regulating glucose homeostasis. Amylin inhibits basal and insulin-stimulated glycogen synthesis in rat skeletal muscle mass [8,9]; it inhibits insulin, somatostatin and glucagon secretion from isolated pancreatic islets and intact perfused pancreas and it reduces post-prandial glucagon and insulin secretion [10-12]. Amylin may also contribute to glycaemic control by slowing gastric emptying [13]. It addition to these physiological functions, amylin is believed to play significant role in the pathogenesis of diabetes mellitus. It is the major component of the amyloid deposits in the islets of patients with non-insulin dependent diabetes mellitus [1,2] and deficiency of amylin may contribute the failure of glycaemic control common of insulin-dependent diabetes [14] and in animal studies amylin itself appears to induce insulin resistance [15]. A variety of physiological effects around the gastrointestinal tract have also been explained. Parenteral administration of amylin has an anorectant effect [13], in addition to significantly reducing gastric emptying [16]. A protectant action against reserpine-, and serotonin-induced gastropathy has been explained [17]. Intravenous amylin is usually a potent inhibitor of basal, pentagastrin and 2-deoxy-D-glucose stimulated gastric acid secretion in the rat [18] and amylin reduced acid secretion in the isolated mouse belly preparation [19]. A stimulant effect on serum Syringic acid gastrin has also been reported, although this may have been secondary to the inhibition of acid secretion [20]. Syringic acid In keeping with these actions amylin-binding sites have been detected in rat gastric fundic mucosa [21]. Within the gastrointestinal tract amylin appears to co-localise with other gastrointestinal peptides. Using em in situ /em hybridisation, immunofluorescence and immunocytochemistry, Mulder em et al /em showed that amylin predominantly co-localised with somatostatin in the D-cells of rat and mouse antral mucosa and rat fundic mucosa [22]. A minority of amylin co-localised to separate populations of gastrin-containing cells in the antrum and PYY-containing cells in the fundus. Studies in PDX-1 deficient mice (which fail to develop G-cells) exhibited no alteration in gastric amylin expression, confirming predominant MAPKAP1 expression of amylin within D-cells [23]. These data showing the presence of amylin and amylin receptors, coupled with the pharmacological effects, suggested that amylin might have a paracrine and/or endocrine regulatory and pathophysiological role in the gastric mucosa. However you will find no studies exploring the processes involved in gastric amylin secretion. Such data are a prerequisite for further understanding of gastric amylin physiology. Main cultures of gastric and intestinal endocrine cells have been utilised to examine the physiological and pathophysiological control of several gastrointestinal Syringic acid peptides including gastrin, somatostatin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) [24-30]. The co-localisation of amylin with somatostatin makes the gastric fundic D-cell preparation a useful model to examine the control of amylin secretion at the cellular level. In this study we have examined receptor-dependant and receptor-independent regulation of.
