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

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

Delineation of the anatomical location, cellular origin and molecular basis of gut-derived glucagon secretion

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.

Inclusion Criteria:

• normal kidney function, normal liver function, normal hemoglobin levels

Exclusion Criteria:

• diabetes type 1, first degree relatives with type 2 diabetes