Exenatide regulates cerebral glucose metabolism in brain areas associated with glucose homeostasis and reward system

Giuseppe Daniele, Patricia Iozzo, Marjorie Molina-Carrion, Jack L Lancaster, Demetrio Ciociaro, Eugenio Cersosimo, Devjit Tripathy, Curtis L Triplitt, Peter T Fox, Nicolas Musi, Ralph A Defronzo, Amalia Gastaldelli

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [18F]2-fluoro-2-deoxy-D-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min · kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state.

Original languageEnglish (US)
Pages (from-to)3406-3412
Number of pages7
JournalDiabetes
Volume64
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

Reward
Homeostasis
Glucose
Brain
Glucose Tolerance Test
exenatide
Injections
Fluorodeoxyglucose F18
Appetite
Isotopes
Positron-Emission Tomography
Hypothalamus
Fasting
Placebos
Insulin
Food

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Daniele, G., Iozzo, P., Molina-Carrion, M., Lancaster, J. L., Ciociaro, D., Cersosimo, E., ... Gastaldelli, A. (2015). Exenatide regulates cerebral glucose metabolism in brain areas associated with glucose homeostasis and reward system. Diabetes, 64(10), 3406-3412. https://doi.org/10.2337/db14-1718

Exenatide regulates cerebral glucose metabolism in brain areas associated with glucose homeostasis and reward system. / Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack L; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis L; Fox, Peter T; Musi, Nicolas; Defronzo, Ralph A; Gastaldelli, Amalia.

In: Diabetes, Vol. 64, No. 10, 01.10.2015, p. 3406-3412.

Research output: Contribution to journalArticle

Daniele, G, Iozzo, P, Molina-Carrion, M, Lancaster, JL, Ciociaro, D, Cersosimo, E, Tripathy, D, Triplitt, CL, Fox, PT, Musi, N, Defronzo, RA & Gastaldelli, A 2015, 'Exenatide regulates cerebral glucose metabolism in brain areas associated with glucose homeostasis and reward system', Diabetes, vol. 64, no. 10, pp. 3406-3412. https://doi.org/10.2337/db14-1718
Daniele, Giuseppe ; Iozzo, Patricia ; Molina-Carrion, Marjorie ; Lancaster, Jack L ; Ciociaro, Demetrio ; Cersosimo, Eugenio ; Tripathy, Devjit ; Triplitt, Curtis L ; Fox, Peter T ; Musi, Nicolas ; Defronzo, Ralph A ; Gastaldelli, Amalia. / Exenatide regulates cerebral glucose metabolism in brain areas associated with glucose homeostasis and reward system. In: Diabetes. 2015 ; Vol. 64, No. 10. pp. 3406-3412.
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