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Impact of energy turnover on the regulation of glucose homeostasis in healthy subjects.

ABSTRACT: OBJECTIVE:Sedentary lifestyle increases the risk of type 2 diabetes. The aim of this study was to investigate the impact of different levels of energy turnover (ET; low, medium, and high level of physical activity and the corresponding energy intake) on glucose metabolism at zero energy balance, caloric restriction, and overfeeding. METHODS:Sixteen healthy individuals (13 men, 3 women, 25.1?±?3.9 years, BMI 24.0?±?3.2?kg/m2) participated in a randomized crossover intervention under metabolic ward conditions. Subjects passed 3?×?3 intervention days. Three levels of physical activity (PAL: low 1.3, medium 1.6, and high 1.8 achieved by walking at 4?km/h for 0, 3?×?55, or 3?×?110?min) were compared under three levels of energy balance (zero energy balance (EB): 100% of energy requirement (Ereq); caloric restriction (CR): 75% Ereq, and overfeeding (OF): 125% Ereq). Continuous interstitial glucose monitoring, C-peptide excretion, and HOMA-IR, as well as postprandial glucose and insulin were measured. RESULTS:Daylong glycemia and insulin secretion did not increase with higher ET at all conditions of energy balance (EB, CR, and OF), despite a correspondingly higher CHO intake (? low vs. high ET: +86 to 135?g of CHO/d). At CR, daylong glycemia (p?=?0.02) and insulin secretion (p?=?0.04) were even reduced with high compared with low ET. HOMA-IR was impaired with OF and improved with CR, whereas ET had no effect on fasting insulin sensitivity. A higher ET led to lower postprandial glucose and insulin levels under conditions of CR and OF. CONCLUSION:Low-intensity physical activity can significantly improve postprandial glycemic response of healthy individuals, independent of energy balance.

SUBMITTER: Busing F

PROVIDER: S-EPMC6687696 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Impact of energy turnover on the regulation of glucose homeostasis in healthy subjects.

Büsing Franziska F Hägele Franziska Anna FA Nas Alessa A Hasler Mario M Müller Manfred James MJ Bosy-Westphal Anja A

Nutrition & diabetes 20190808 1

<h4>Objective</h4>Sedentary lifestyle increases the risk of type 2 diabetes. The aim of this study was to investigate the impact of different levels of energy turnover (ET; low, medium, and high level of physical activity and the corresponding energy intake) on glucose metabolism at zero energy balance, caloric restriction, and overfeeding.<h4>Methods</h4>Sixteen healthy individuals (13 men, 3 women, 25.1 ± 3.9 years, BMI 24.0 ± 3.2 kg/m<sup>2</sup>) participated in a randomized crossover interv ...[more]

PMID: 31395858

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Project description:Aims/hypothesisThe brain is a major consumer of glucose as an energy source and regulates systemic glucose as well as energy balance. Although glucose transporters such as GLUT2 and sodium-glucose cotransporter 2 (SGLT2) are known to regulate glucose homeostasis and metabolism, the identity of a receptor that binds glucose to activate glucose signalling pathways in the brain is unknown. In this study, we aimed to discover a glucose receptor in the mouse hypothalamus.MethodsHere we used a high molecular mass glucose-biotin polymer to enrich glucose-bound mouse hypothalamic neurons through cell-based affinity chromatography. We then subjected the enriched neurons to proteomic analyses and identified adhesion G-protein coupled receptor 1 (ADGRL1) as a top candidate for a glucose receptor. We validated glucose-ADGRL1 interactions using CHO cells stably expressing human ADGRL1 and ligand-receptor binding assays. We generated and determined the phenotype of global Adgrl1-knockout mice and hypothalamus-specific Adgrl1-deficient mice. We measured the variables related to glucose and energy homeostasis in these mice. We also generated an Adgrl1Cre mouse model to investigate the role of ADGRL1 in sensing glucose using electrophysiology.ResultsAdgrl1 is highly expressed in the ventromedial nucleus of the hypothalamus (VMH) in mice. Lack of Adgrl1 in the VMH in mice caused fasting hyperinsulinaemia, enhanced glucose-stimulated insulin secretion and insulin resistance. In addition, the Adgrl1-deficient mice had impaired feeding responses to glucose and fasting coupled with abnormal glucose sensing and decreased physical activity before development of obesity and hyperglycaemia. In female mice, ovariectomy was necessary to reveal the contribution of ADGRL1 to energy and glucose homeostasis.Conclusions/interpretationAltogether, our findings demonstrate that ADGRL1 binds glucose and is involved in energy as well as glucose homeostasis in a sex-dependent manner. Targeting ADGRL1 may introduce a new class of drugs for the treatment of type 2 diabetes and obesity.

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Impact of energy turnover on the regulation of glucose homeostasis in healthy subjects.

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Impact of energy turnover on the regulation of glucose homeostasis in healthy subjects.

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