Glucagon-like peptide 1 immunoreactivity in gastroentero-pancreatic endocrine tumors: a light- and electron-microscopic study

Abstract

The preproglucagon gene encodes, in addition to glucagon, two smaller peptides with structural similarity: glucagon-like peptides 1 and 2. Glucagon-like peptide 1 (GLP-1) 7-36 amide is the most powerful incretin candidate. In the present study, GLP-1 immunoreactivity was investigated in tissue specimens of various types of gastroenteropancreatic tumors, and the serum-levels of GLP-1 were assayed. Immunohistochemical staining of 88 tumors revealed GLP-1 immunoreactivity in 17 neoplasias (19.3%), viz., in 7 out of 33 non-functioning tumors, 4 out of 20 gastrinomas, 4 out of 13 insulinomas, 1 out of 3 vasoactive-intestinal-polypeptide (VIP)omas and 1 adrenocorticotropic-hormone (ACTH)-producing tumor. In these tumors, GLP-1-immunoreactive cells were distributed either diffusely, arranged in clusters, or as single cells. All GLP-1-positive tumors were immunoreactive for glucagon or glicentin, 10 tumors were immunoreactive for pancreatic polypeptide, and 8 tumors for insulin. Ultrastructural analysis of 8 GLP-1-positive tumors, with the immunogold technique, demonstrated GLP-1 immunoreactivity mainly in cells resembling the A-cells of the pancreas or the L-cells of the gut. Of the 17 GLP-1-immunoreactive tumors, 15 were primarily located in the pancreas. Additionally, 2 non-functioning tumors of the rectum were GLP-1 immunoreactive. Five tumors were GLP-1 immunoreactive from 9 patients with multiple endocrine neoplasia I syndrome. Patients with GLP-1-immunoreactive tumors were characterized by a significantly lower rate of distant metastases (P < 0.01) and a higher rate of curative resections (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Glial Fibrillary Acidic Protein (GFAP)-like Immunoreactivity in Rat Endocrine Pancreas

“…Moreover, even though restricted to glucagon-secreting elements, GFAP expression should be added to an already long list of markers shared by the endocrine and nervous systems (Le Douarin 1988;Teitelman 1991;Larsson 1998). In particular, glucagon cells constantly or transiently express molecules that have been also reported in the nervous system, such as glucagon-like peptide-1 and glucagon-like peptide-2 (Eissele et al 1994;Larsen et al 1997), tyrosine hydroxylase (Alpert et al 1988), neuron-specific enolase (Lloyd et al 1984), the 67-kD isoform of the glutamic acid decarboxylase (Li et al 1995), chromogranins (Schmid et al 1994), synaptophysin (Bouwens et al 1997), insulin (Larsson 1998), and PYY (Larsson 1998). However, we emphasize that by the use of several different technical approaches, such as the removal of the entire ectoderm from embryonic rats (Pictet et al 1976) or the generation of chimeric chick-quail embryos (Andrew 1976;Fontaine and Le Douarin 1977), the hypothesis that pancreatic endocrine precursors reside in the neural crest appears less likely (Le Douarin 1988).…”

Altered expression of aquaporin 4 and H+/K+‐ATPase in the stomachs of peptide YY (PYY) transgenic mice

“…Currently, the regulation of acid secretion is believed to occur in phases, frequently termed cephalic, gastric and intestinal phases. PYY (peptide YY) is released post‐prandially from the L‐type endocrine cells in the ileum and colon into the blood, in response to meal ingestion (Varndell et al, 1985; Eissele et al, 1994). PYY displays a potent inhibition of cephalic and gastric phases of gastric acid secretion by both central and peripheral mechanisms (Yang, 2002).…”

Glucagon Secreting Cells Responds to Insulin Secretion In vitro Using Immunocytochemistry

“…Several workers have fruitfully employed the immunocytochemistry method to investigate the cellular response in pancreas and other tissue. [19–21] Some information on the role of insulin in regulating glucagon secreting cells is also available using in vitro studies; Maruyama et al . 1984 reported intrapancreatic insulin in rat exerted an ongoing release inhibiting action on the alpha cells.…”