Introduction and Objective: Incretin therapies exert important effects on the central nervous system (CNS) through incompletely understood mechanisms. We previously showed that brain glucose responses to hyperglycemic clamp are altered in diabetes and obesity. However, standard clamp-based assessments of brain glucose uptake and metabolism do not allow evaluation of a potential role for the incretin effect in regulating brain metabolism. In this study, we tested whether oral and intravenous (IV) dextrose differentially alter brain glucose uptake during acute hyperglycemia in humans.Methods: Healthy adults underwent two separate brain scanning sessions with a hyperglycemic clamp (target 180 mg/dL) coupled with or without oral ingestion of 125 grams (20 oz.) dextrose. The change in brain glucose was measured by 1H magnetic resonance spectroscopy scanning at 3 Tesla. GLP-1, GIP, and insulin were measured by ELISA.Results: Nine healthy adults participated in the study (age 29 ± 7.1 years, BMI 23.5 ± 2.3 kg/m2, A1c 5.1 ± 0.3%); seven participants completed both study conditions. Plasma glucose (p=0.31) and the glucose infusion rate (p=0.09, both by mixed effects analysis) were similar between conditions. Oral dextrose consumption increased GLP-1 (10.7 ± 7.0 vs. 2.2 ± 0.7 pmol/L, p=0.04) and GIP (41.9 ± 15.1 vs. 3.7 ± 1.5 pmol/L, p<0.001, both at 30”) as expected. The change in brain glucose normalized to plasma glucose was higher with oral dextrose compared to IV dextrose alone (p=0.04, mixed effects analysis).Conclusion: Oral feeding enhanced brain glucose uptake beyond that induced by equivalent changes generated by IV dextrose alone. These data suggest a potential role for intestinal-derived factors in glucose disposal and energy generation in the brain and potential mechanism underlying CNS effects of incretin therapies.
B.C. Matson: None. W. Chang: None. A. Coppoli: Consultant; Ended; Merck Sharp & Dohme Corp. J.J. Palmiotto: None. E.Y. Wang: None. K. Eswar: None. G.F. Mason: Consultant; Ended; Merck Sharp & Dohme Corp. Consultant; Current; Leal Therapeutics. J.J. Hwang: None.
Endocrine Fellows Foundation
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