The nutrient-dependent glucagon-like peptide-1 (7-36) amide (GLP-1) release was studied in comparison to the glucose-dependent insulin-releasing polypeptide (GIP) response in 10 healthy volunteers each undergoing various protocols. Plasma samples were saved up to 120 min after challenges by oral, intravenous or intraduodenal administration of nutrients. Basal plasma-GLP-1 concentrations ranged between 0.4 and 1.4 pM, maximal postprandial GLP-1 levels peaked between 10 and 12 pM. Intravenous glucose (25 g i.v.) did not change basal GLP-1 levels. Oral administration of glucose (50 g) induced a biphasic GLP-1 release peaking at 30-60 min and a biphasic GIP release peaking at 5 and 45 min. This increase paralleled the secretion of insulin. Oral galactose (100 g) and amino acids (25 g) also induced a rapid plasma GLP-1 response. After fat (67 g corn oil) a strong and long-lasting ( > 120 min) increase of GLP-1 plasma levels occurred. When a mixed liquid meal was given (6 g soybean oil, 5g casein, 13 g glucose) immunoreactive (IR)-GLP-l rapidly increased and peaked after 5 min with declining levels after 30 min. In response to an intraduodenal infusion of a small glucose load (5.34 g within 120 min) a rapid, short-lasting GLP-1 response occurred whereas plasma GIP and insulin levels remained unaltered. Luminal perfusion of an isolated vascularly perfused rat ileum with a polydiet induced a rapid rise of portally released IR-GLP-1 which was followed by a sustained release. Glucose evoked sodium-dependently a sharp increase of IR-GLP-1 levels followed by a plateau release. The intraluminal infusion of a mixture of amino acids or fat was without any effect on IR-GLP-1. We hypothesize that in contrast to GIP the GLP-1 release from L cells is triggered by nervous reflexes, by putative humoral factor(s) being released from the upper small intestine in addition to nutrient stimuli acting at the luminal surface of the gut.

Recent data revealed the existence of specific receptors for glucagon-like peptide-1(7-36)amide (GLP-1) on rat lung membranes. Utilizing slide-mount autoradiography of fresh frozen lung tissue sections, we have localized binding sites for GLP-1 on mucous glands in the trachea and on vascular smooth muscle of the pulmonary artery. When tracheas were incubated in a modified Ussing chamber, the addition of GLP-1 to the submucosal side increased 35S-sulfate-labeled macromolecule secretion (191 +/- 12% above basal, P < 0.005). The optimal secretory response elicited by GLP-1 was approximately 23% of the maximal secretory response after a maximal acetylcholine stimulation. Other proglucagon-derived peptides such as glucagon, oxyntomodulin, and GLP-2 had no effect. In isolated rings of arteries, GLP-1 (10(-8) to 10(-5) M) induced a dose-dependent and time-reversible relaxation of preconstricted arteries. In a preparation with denuded epithelium, GLP-1 lost its effect. In conclusion, GLP-1 might represent another neuropeptide that acts as neurotransmitter of the peptidergic, nonadrenergic-noncholinergic nervous system that innervates the airways.

Early identification of pancreaticoduodenal endocrine tumors (PETs) in multiple endocrine neoplasia type 1 (MEN-1) is mandatory, because these tumors represent the most common cause of death within the syndrome. The diagnostic value of imaging procedures has therefore been evaluated in a prospective observational study. Between December 1997 and June 2003 twenty-two MEN-1 patients with genetically confirmed disease were followed for PETs using a standardized screening program with serum hormone measurements, endoscopic ultrasonography (EUS), computed tomography (CT), and somatostatin-receptor scintigraphy (SRS). Results could be validated by surgery and histopathology in 13 patients during 18 operations. In 12 asymptomatic patients with tumors measuring 10 mm or less, who have not yet undergone operation, PETs were detected by EUS in 12/12, by CT in 1/12, and by SRS in 2/11 cases. In 13 patients who have undergone surgical exploration EUS, CT, and SRS were true positive in 12 of 16, 7 of 13, and 12 of 17 cases, respectively, although the number of tumors detected by each imaging procedure alone was lower than the number detected intraoperatively and histopathologically in almost every case. A solitary liver metastasis in one patient and a nonfunctioning PET recurrence in another were identified only by SRS. Endoscopic ultrasonography is the most sensitive imaging procedure for the detection of small (< or = 10 mm) PETs in MEN-1, whereas SRS is the procedure of choice for the identification of metastases of MEN-1 PETs-i.e., for staging. Detection of PETs at an early stage by an aggressive screening program using EUS may lead to prompt surgical intervention and improved prognosis of MEN-1 PETs.

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