| Autor: |
Grøndahl, Magnus F.G., Lange, Andreas H., Suppli, Malte P., Bagger, Jonatan I., Thing, Mira, Gluud, Lise L., Kofod, Dea H., Hornum, Mads, van Hall, Gerrit, Trammell, Samuel A.J., Grevengoed, Trisha J., Hartmann, Bolette, Holst, Jens J., Vilsbøll, Tina, Christensen, Mikkel B., Lund, Asger B., Knop, Filip K. |
| Předmět: |
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| Zdroj: |
Diabetes; Oct2024, Vol. 73 Issue 10, p1641-1647, 7p |
| Abstrakt: |
It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n = 16), individuals with Child-Pugh A–C cirrhosis (n = 16), and matched control individuals (n = 16), before, during, and after a 60-min glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) compared with both individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] min) compared with individuals with cirrhosis (5.7 [5.2;6.3] min, P = 0.002) and control individuals (5.7 [5.2;6.3] min, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, CKD, but not liver cirrhosis, leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination. Article Highlights: This study was undertaken to gain insights into the elimination of glucagon in humans, as this is an important, yet not fully uncovered, part of glucagon physiology. We investigated whether individuals with chronic kidney disease or liver cirrhosis were characterized by an altered elimination of glucagon. We found that individuals with stage 4 chronic kidney disease exhibit a significantly reduced elimination of glucagon, while patients with liver cirrhosis have a preserved glucagon elimination. Our findings support the kidneys as the prevailing site of glucagon elimination in humans and shed light on glucagon-related pathophysiology in liver and kidney diseases. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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