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Ghrelin mediates glucose metabolism after food intake
In healthy adults, exogenous ghrelin impairs beta-cell and glucose responses to food consumption and triggers acute insulin resistance, according to recent findings.
Jenny Tong, MD, MPH, associate professor in the division of endocrinology, metabolism and nutrition at Duke University Medical Center, and colleagues evaluated 13 healthy volunteers aged 19 to 31 years without diabetes or impaired fasting glucose (mean age 23.7 years; 8 men; mean BMI, 24 kg m2; mean fasting blood glucose, 5.3 nM; mean fasting plasma insulin, 60.8 pM). Following a 10- to 12-hour fast, participants received infusions of either saline or synthetic human acyl-ghrelin (doses of 0.26 and 2.0 µg/kg/h) on three study visits, in random order, separated by a minimum of 1 week. Infusions were given for 45 minutes to attain steady-state levels and continued for 240 minutes after consumption of a liquid mixed-nutrient meal. The test meal consisted of 45% carbohydrate, 15% protein and 40% fat, and was ingested over a 10-minute period. A total of 20 blood samples were then taken at scheduled intervals throughout an additional 180-minute period. Fasting levels of insulin and glucose were taken as the mean of samples drawn prior to ghrelin infusion, and basal levels were assayed from 15 minutes to immediately prior to the meal tolerance test. The study’s primary outcomes were area under the curve (AUC) for glucose and insulin secretion.
Jenny Tong
Researchers found that following the low-dose acyl ghrelin infusion, total ghrelin level increased to 1.7-fold the fasting value; following the higher dose, total ghrelin level increased to 4.8-fold the fasting value. Acyl ghrelin was increased to approximately 9- and 51-fold, respectively, above the levels at baseline. Intravenous infusion of ghrelin for 45 minutes had negligible effects on fasting plasma glucose or insulin levels. However, during the 4-hour meal tolerance test, ghrelin infusion at both doses increased glucose AUC vs. saline, which suggests worsened glucose tolerance, according to researchers.
During the high-dose ghrelin infusion, post-meal insulin and C-peptide levels increased vs. saline infusion; low-dose ghrelin infusion did not influence the AUC of insulin or C-peptide. When beta-cell function was adjusted for blood glucose concentration as AUC ISR/AUC G0 -180min, a significant reduction in this value was seen with the high-dose infusion of ghrelin but not the low-dose. The high- but not low-dose ghrelin infusion also significantly decreased insulin sensitivity, computed as OGIS 0-180 min.
Ghrelin reduced insulin sensitivity, impaired beta-cell function and promoted glucose intolerance during the meal tolerance test. Moreover, high-dose ghrelin infusion increased post-meal GLP-1 exudation with no impact on GIP, glucagon or PYY levels.
“The effect of ghrelin on glucose metabolism in humans is complex,” Tong told Endocrine Today. “Raising circulating ghrelin to a supraphysiologic level in the fasting and postprandial states decreases insulin sensitivity and impairs glucose tolerance in healthy men and women. The increase in postprandial GLP-1 secretion by ghrelin suggests a novel enteroendocrine connection. Blocking (acyl) ghrelin action or synthesis may improve glucose tolerance but may also be at an expense of decreased postprandial GLP-1 secretion. The metabolic consequences of these multifaceted interactions will need to be elucidated in future studies.” – by Jennifer Byrne
For more information:
Jenny Tong, MD, MPH, can be reached at jenny.tong@duke.edu.
Disclosure: The researchers report no relevant disclosures.