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

NCT ID: NCT00639613


Title
Exspression of Prohormone Convertase 1 and 2 in Small Intestinal Endocrine Mucosa Cells in Patients With Type 2 Diabetes
Purpose
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.
Details
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
Keywords
Source
University Hospital, Gentofte, Copenhagen
Sponsors
University Hospital, Gentofte, Copenhagen
Status
Completed
Acronym
T2DM-PC1-2
Last Updated
24 Jun 2015
URL
Official Link
Locations
Denmark