Norepinephrine transporter expression is inversely associated with glycaemic indices: a pilot study in metabolically diverse persons with overweight and obesity.
The objective of this study was to examine the cross-sectional relationship between the expression of norepinephrine transporter (NET), the protein responsible for neuronal uptake-1, and indices of glycaemia and hyperinsulinaemia, in overweight and obese individuals.



Thirteen non-medicated, non-smoking subjects, aged 58 ± 1 years (mean ± standard error of the mean), body mass index (BMI) 31.4 ± 1.0 kg m-2, with wide-ranging plasma glucose and haemoglobin A1c (HbA1c, range 5.1% to 6.5%) participated. They underwent forearm vein biopsy to access sympathetic nerves for the quantification of NET by Western blot, oral glucose tolerance test (OGTT), euglycaemic hyperinsulinaemic clamp, echocardiography and assessments of whole-body norepinephrine kinetics and muscle sympathetic nerve activity.



Norepinephrine transporter expression was inversely associated with fasting plasma glucose (r= -0.62,P= 0.02), glucose area under the curve during OGTT (AUC0-120,r= -0.65,P= 0.02) and HbA1c (r= -0.67,P= 0.01), and positively associated with steady-state glucose utilization during euglycaemic clamp (r= 0.58,P= 0.04). Moreover, NET expression was inversely related to left ventricular posterior wall dimensions (r= -0.64,P= 0.02) and heart rate (r= -0.55,P= 0.05). Indices of hyperinsulinaemia were not associated with NET expression. In stepwise linear regression analysis adjusted for age, body mass index and blood pressure, HbA1c was an independent inverse predictor of NET expression, explaining 45% of its variance.



Hyperglycaemia is associated with reduced peripheral NET expression. Further studies are required to identify the direction of causality.
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
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Straznicky
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
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L
Guo
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
S J
SJ
Corcoran
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
M D
MD
Esler
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
S E
SE
Phillips
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
C I
CI
Sari
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
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MT
Grima
Alfred Baker Medical Unit Baker IDI Heart & Diabetes Institute Melbourne Australia.
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Karapanagiotidis
Alfred Baker Medical Unit Baker IDI Heart & Diabetes Institute Melbourne Australia; Cardiology, Western Health University of Melbourne Melbourne Australia.
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Wong
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
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Eikelis
Heart Failure Research Group Baker IDI Heart & Diabetes Institute Melbourne Australia; Faculty of Medicine, Nursing and Health Sciences Monash University Melbourne Australia.
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JA
Mariani
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia.
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Kobayashi
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia; Primary Health Care Monash University Melbourne Australia.
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JB
Dixon
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia; Faculty of Medicine, Nursing and Health Sciences Monash University Melbourne Australia.
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Lambert
Human Neurotransmitters Laboratory Baker IDI Heart & Diabetes Institute Melbourne Australia; Departments of Physiology Monash University Melbourne Australia; Departments of Physiology University of Melbourne Melbourne Australia.
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EA
Lambert
Hyperglycaemia; norepinephrine transporter; obesity; sympathetic nervous system