NCT00639613

The Role of Small Intestinal Endocrine Cells in Type 2 Diabetic Hyperglucagonemia

Exspression of Prohormone Convertase 1 and 2 in Small Intestinal Endocrine Mucosa Cells in Patients With Type 2 Diabetes

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 20 (actual)
• Sponsor: University Hospital, Gentofte, Copenhagen · Academic / Other
• Sex: All
• Age: 35 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to determine whether excessive secretion of glucagon in type 2 diabetes originates from the pancreatic alpha-cells or endocrine cells in the mucosa of the small intestinal.

Detailed description

Hyperglucagonemia contributes significantly to the hyperglycemia characterizing patients with Type 2 diabetes. Fasting hyperglucagonemia induces hepatic glucose release resulting in elevated fasting levels of plasma glucose. Furthermore, lack of postprandial suppression of glucagon secretion - exchanged for a paradoxical postprandial hypersecretion of glucagon - results in increased levels of postprandial plasma glucose. Additionally, type 2 diabetes is characterized by decreased postprandial responses of the insulinotropic (and glucagonostatic) peptide hormone glucagon-like peptide-1 (GLP-1). Recent studies from our group suggest that the intestines are involved in the diminshed suppression of glucagon following ingestion of nutrients. Thus, suppression of glucagon during oral glucose ingestion diminishes and reverses to stimulation while suppression during intravenous administered glucose sustains along with development of glucose intolerance. In the small intestines mucosal endocrine L-cells secrete GLP-1, which is processed from its precursor, proglucagon, by prohormone convertase 1 (PC1). In the pancreatic alpha-cells proglucagon is processed to glucagon via prohormone convertase 2 (PC2). We plan to examine biopsies from the mucosa of the small intestines from patients with type 2 diabetes and from healthy subjects for glucagon production. Furthermore, the volunteers will be subjected to a standard meal test in order to correlate the gene expression studies with the level of postprandial hyperglucagonemia of the subjects.

Conditions

• Type 2 Diabetes

Interventions

Type	Name	Description
PROCEDURE	Double-balloon enteroscopy	Double-balloon enteroscopy allows for the entire gastrointestinal tract to be visualized in real time. The technique involves the use of a balloon at the end of a special enteroscope camera and an overtube, which is also fitted with a balloon. The procedure is usually done with the use of conscious sedation. The enteroscope and overtube are inserted through the mouth and passed in conventional fashion (that is, as with gastroscopy) into the small bowel. Following this, the endoscope is advanced a small distance in front of the overtube and the balloon at the end is inflated. Using the assistance of friction at the interface of the enteroscope and intestinal wall, the small bowel is accordioned back to the overtube. The overtube balloon is then deployed, and the enteroscope balloon is deflated. The process is then continued until the entire small bowel is visualized. Double-balloon enteroscopy allows for the sampling or biopsying of small bowel mucosa.
OTHER	Standard meal test	Liquid meal consisting of 100 g "Ny NAN" dissolved in 300 ml water (ca. 5000 kJ) to be ingested over 5 minutes. Blood will be sampled for 4 hours following ingestion. Samples are centrifuges and plasma will be analysed for glucagon, GLP-1, GIP, insulin and C-peptide concentrations.

Timeline

• Start date: 2008-03-01
• Primary completion: 2015-06-01
• First posted: 2008-03-20
• Last updated: 2015-06-26

Locations

1 site across 1 country: Denmark