| Autor: |
BAEKDAL, MILLE, LUND, ASGER B., WEWER ALBRECHTSEN, NICOLAI JACOB, EGHOLK, JOHAN I., JORSAL, TINA, JUEL, CAROLINE T., GALSGAARD, KATRINE D., HUNT, JENNA, REHFELD, JENS F., RIGBOLT, KRISTOFFER, FRIIS, STEFFEN U., ORSKOV, CATHRINE, POULSEN, STEEN SEIER, HOLST, JENS J., VILSBØLL, TINA, KNOP, FILIP K. |
| Zdroj: |
Diabetes; 2019 Supplement, Vol. 68, pN.PAG-N.PAG, 1p |
| Abstrakt: |
We have previously shown that totally pancreatectomized patients (PX) and patients with type 2 diabetes (T2D) exhibit hypersecretion of glucagon in response to oral glucose stimulation whereas intravenous glucose suppresses plasma concentrations of glucagon. Here, we evaluated the expression of the gene encoding glucagon (GCG), glucagon peptide content and density of glucagon-positive cells in mucosal biopsies from the upper gastrointestinal tract of PX patients, patients with T2D and nondiabetic controls. Eight PX patients, eight patients with T2D and eight sex, age and BMI-matched healthy controls underwent upper enteroscopy with intestinal biopsy sampling followed by an intraluminal infusion of 100 ml 50% (w/v) glucose solution with frequent blood sampling. The mucosal biopsies were subjected to mRNA sequencing, immunohistochemistry using a new glucagon-directed C-terminal monoclonal antibody, peptide extraction and subsequent measurements of tissue concentrations of glucagon and other proglucagon-derived peptides. GCG expression in the small intestine was 3 to 4-fold higher in PX and T2D patients compared to controls (P<0.01). Extractable glucagon in small intestinal biopsies was 12-fold greater in PX and 5-fold greater in T2D compared to controls (P<0.05). The density of glucagon-positive cells was more than 3-fold higher in PX compared to controls (P<0.05). Plasma glucagon responses to intraluminal administration of glucose was significantly higher in PX and T2D (649±206 vs. 557±142 pmol/l × min [mean±SEM], P
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| Databáze: |
Complementary Index |
| Externí odkaz: |
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