The Anatomical Location, Cellular Origin and Molecular Basis of Gut-derived Glucagon Secretion

Study Overview
=================
Brief Summary
-----------------
Delineation of the anatomical location, cellular origin and molecular basis of gut-derived glucagon secretion

Detailed Description
-----------------
Aim: to delineate the anatomical origin, the molecular structure and precursors, the regulation and the (patho-) physiological implications of gut-derived glucagon. Eight totally pancreatectomised patients, eight type 2 diabetes patients and eight healthy controls (age 18-80, BMI <30) with normal kidney and liver parameters and hgb> 6.5 - will be included. The participants will each undergo one screening day and one study day including a gastroduodenoscopy. Multiple biopsies will be taken at several predefined locations in the upper gastrointestinal tract. These biopsies will be analysed with different techniques including immunohistochemical staining, quantitative polymerase chain reaction (qPCR-) analyses and more to search for glucagon. After the last biopsy has been collected, 50 g of glucose dissolved in 100 ml water is infused through the enteroscope into the most proximal part of the small intestine. Hereafter blood samples for glucagon and gut hormone analyses will be collected 15, 30 and 45 min after the glucose infusion.

Official Title
-----------------
The Anatomical Location, Cellular Origin and Molecular Basis of Gut-derived Glucagon Secretion

Conditions
-----------------
Glucose Metabolism Disorders

Intervention / Treatment
-----------------
* Other: Oral glucose tolerance test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: normal kidney function, normal liver function, normal hemoglobin levels Exclusion Criteria: diabetes type 1, first degree relatives with type 2 diabetes

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Totally pancreatectomised patients<br>Oral glucose tolerance test and biopsies | Other: Oral glucose tolerance test<br>* Oral glucose tolerance test and biopsies<br>|
| Active Comparator: Type 2 diabetes patients<br>Oral glucose tolerance test and biopsies | Other: Oral glucose tolerance test<br>* Oral glucose tolerance test and biopsies<br>|
| Active Comparator: Healthy control subjects<br>Oral glucose tolerance test and biopsies | Other: Oral glucose tolerance test<br>* Oral glucose tolerance test and biopsies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gut-derived glucagon | The primary objective is to investigate mucosal biopsies from specific regions of the upper gastrointestinal tract | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral glucose tolerance test | Glucose metabolism - hormones, insulin, glucagon, glp-1 | 45 minutes |