Brain substrate metabolism and ß-cell function in humans: A positron emission tomography study

Eleni Rebelos; Andrea Mari; Marco Bucci; Miikka-Juhani Honka; Jarna C Hannukainen; Kirsi A Virtanen; Jussi Hirvonen; Lauri Nummenmaa; Martin Heni; Patricia Iozzo; Ele Ferrannini; Pirjo Nuutila

doi:10.1002/edm2.136

Brain substrate metabolism and ß-cell function in humans: A positron emission tomography study

Endocrinol Diabetes Metab. 2020 Apr 19;3(3):e00136. doi: 10.1002/edm2.136. eCollection 2020 Jul.

Authors

Eleni Rebelos¹, Andrea Mari², Marco Bucci¹, Miikka-Juhani Honka¹, Jarna C Hannukainen¹, Kirsi A Virtanen^{1

3}, Jussi Hirvonen⁴, Lauri Nummenmaa^{1

5}, Martin Heni^{6

7

8}, Patricia Iozzo^{1

9}, Ele Ferrannini⁹, Pirjo Nuutila^{1

10}

Affiliations

¹ Turku PET Centre University of Turku Turku Finland.
² Institute of Neuroscience National Research Council Padua Italy.
³ Clinical Nutrition Institute of Public Health and Clinical Nutrition University of Eastern Finland (UEF) Kuopio Finland.
⁴ Department of Radiology Turku University Hospital and University of Turku Turku Finland.
⁵ Department of Psychology University of Turku Turku Finland.
⁶ Department of Internal Medicine Division of Endocrinology Diabetology, Angiology, Nephrology and Clinical Chemistry Eberhard Karls University Tuebingen Tuebingen Germany.
⁷ Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tuebingen Tuebingen Germany.
⁸ German Center for Diabetes Research (DZD e.V.) Neuherberg Germany.
⁹ Institute of Clinical Physiology National Research Council (CNR) Pisa Italy.
¹⁰ Department of Endocrinology Turku University Hospital Turku Finland.

Abstract

Aims: Recent clinical studies have shown enhanced brain glucose uptake during clamp and brain fatty acid uptake in insulin-resistant individuals. Preclinical studies suggest that the brain may be involved in the control of insulin secretion. The aim of this study was to investigate whether brain metabolism assessed as brain glucose and fatty acid uptake is associated with the parameters of β-cell function in humans.

Materials and methods: We analysed cross-sectional data of 120 subjects across a wide range of BMI and insulin sensitivity. Brain glucose uptake (BGU) was measured during euglycaemic-hyperinsulinaemic clamp (n = 67) and/or during fasting (n = 45) using [¹⁸F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). In another group of subjects (n = 34), brain fatty acid uptake was measured using [¹⁸F]-fluoro-6-thia-heptadecanoic acid (FTHA) PET during fasting. The parameters of β-cell function were derived from OGTT modelling. Statistical analysis was performed with whole-brain voxel-based statistical parametric mapping.

Results: In non-diabetics, BGU during euglycaemic hyperinsulinaemic clamp correlated positively with basal insulin secretion rate (r = 0.51, P = .0008) and total insulin output (r = 0.51, P = .0008), whereas no correlation was found in type 2 diabetics. BGU during clamp correlated positively with potentiation in non-diabetics (r = 0.33, P = .02) and negatively in type 2 diabetics (r = -0.61, P = .02). The associations in non-diabetics were not explained with whole-body insulin sensitivity or BMI. No correlations were found between baseline (fasting) BGU and basal insulin secretion rate, whereas baseline brain fatty acid uptake correlated directly with basal insulin secretion rate (r = 0.39, P = .02) and inversely with potentiation (r = -0.36, P = .04).

Conclusions: Our study provides coherent, though correlative, evidence that, in humans, the brain may be involved in the control of insulin secretion independently of insulin sensitivity.

Keywords: brain glucose uptake; free fatty acids; glucose‐induced potentiation; insulin secretion; positron emission tomography.