MOLECULAR AND FUNCTIONAL CHANGES IN GLUCOKINASE EXPRESSION IN THE BRAINSTEM DORSAL VAGAL COMPLEX IN A MURINE MODEL OF TYPE 1 DIABETES

被引:18
作者
Halmos, K. C. [1 ,2 ]
Gyarmati, P. [1 ]
Xu, H. [1 ]
Maimaiti, S. [1 ]
Jancso, G. [2 ]
Benedek, G. [2 ]
Smith, B. N. [1 ]
机构
[1] Univ Kentucky, Dept Physiol, Coll Med, Lexington, KY 40536 USA
[2] Univ Szeged, Dept Physiol, H-6720 Szeged, Hungary
关键词
GABA neuron; hyperglycemia; K-ATP channel; nucleus tractus solitarius; postsynaptic current; vagus; MOTOR NUCLEUS; GLUCOSE; NEURONS; INHIBITION; PLASTICITY; LOCALIZATION; HYPOGLYCEMIA; MODULATION; CIRCUITS;
D O I
10.1016/j.neuroscience.2015.08.023
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Glucose concentration changes in the nucleus tractus solitarius (NTS) affect visceral function and metabolism by influencing central vagal circuits, especially inhibitory, GABAergic NTS neurons. Acutely elevated glucose can alter NTS neuron activity, and prolonged hyperglycemia and hypoinsulemia in animal models of type 1 diabetes results in plasticity of neural responses in the NTS. NTS neurons contributing to metabolic regulation therefore act as central glucose sensors and are functionally altered in type 1 diabetes. Glucokinase (GCK) mediates cellular utilization of glucose, linking increased glucose concentration to excitability changes mediated by ATP-sensitive K+ channels (K-ATP). Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and in vitro electrophysiology, we tested the hypothesis that changes in GCK expression in the NTS accompany the development of diabetes symptoms in the streptozotocin (STZ)-treated mouse model of type 1 diabetes. After several days of hyperglycemia in STZ-treated mice, RNA expression of GCK, but not Kir6.2 or SUR1, was decreased versus controls in the dorsal vagal complex. Electrophysiological recordings in vitro indicated that neural responses to acute hyperglycemia, and synaptic responsiveness to blockade of GCK with glucosamine, were attenuated in GABAergic NTS neurons from STZ-treated mice, consistent with reduced molecular and functional expression of GCK in the vagal complex of hyperglycemic, STZ-treated mice. Altered autonomic responses to glucose in type 1 diabetes may therefore involve reduced functional GCK expression in the dorsal vagal complex. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:115 / 122
页数:8
相关论文
共 32 条
[1]  
[Anonymous], 2014, NAT DIAB STAT REP ES, DOI [10.1177/1527154408322560, DOI 10.1177/1527154408322560]
[2]   Enhanced NMDA Receptor-Mediated Modulation of Excitatory Neurotransmission in the Dorsal Vagal Complex of Streptozotocin-Treated, Chronically Hyperglycemic Mice [J].
Bach, Eva C. ;
Halmos, Katalin Cs. ;
Smith, Bret N. .
PLOS ONE, 2015, 10 (03)
[3]   Neuronal responses to transient hypoglycaemia in the dorsal vagal complex of the rat brainstem [J].
Balfour, RH ;
Hansen, AMK ;
Trapp, S .
JOURNAL OF PHYSIOLOGY-LONDON, 2006, 570 (03) :469-484
[4]  
BARBER WD, 1987, GASTROENTEROL CLIN N, V16, P521
[5]   cAMP-dependent insulin modulation of synaptic inhibition in neurons of the dorsal motor nucleus of the vagus is altered in diabetic mice [J].
Blake, Camille B. ;
Smith, Bret N. .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2014, 307 (06) :R711-R720
[6]   Diabetes induces GABA receptor plasticity in murine vagal motor neurons [J].
Boychuk, C. R. ;
Halmos, K. Cs. ;
Smith, B. N. .
JOURNAL OF NEUROPHYSIOLOGY, 2015, 114 (01) :698-706
[7]   Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii [J].
Boychuk, Carie R. ;
Gyarmati, Peter ;
Xu, Hong ;
Smith, Bret N. .
JOURNAL OF NEUROPHYSIOLOGY, 2015, 114 (02) :999-1007
[8]   IN SITU COEXPRESSION OF GLUCOSE AND MONOCARBOXYLATE TRANSPORTER mRNAs IN METABOLIC-SENSITIVE CAUDAL DORSAL VAGAL COMPLEX CATECHOLAMINERGIC NEURONS: TRANSCRIPTIONAL REACTIVITY TO INSULIN-INDUCED HYPOGLYCEMIA AND CAUDAL HINDBRAIN GLUCOSE OR LACTATE REPLETION DURING INSULIN-INDUCED HYPOGLYCEMIA [J].
Briski, K. P. ;
Cherian, A. K. ;
Genabai, N. K. ;
Vavaiya, K. V. .
NEUROSCIENCE, 2009, 164 (03) :1152-1160
[9]   Modulation of gastrointestinal vagal neurocircuits by hyperglycemia [J].
Browning, Kirsteen N. .
FRONTIERS IN NEUROSCIENCE, 2013, 7
[10]   Intestinal Cholecystokinin Controls Glucose Production through a Neuronal Network [J].
Cheung, Grace W. C. ;
Kokorovic, Andrea ;
Lam, Carol K. L. ;
Chari, Madhu ;
Lam, Tony K. T. .
CELL METABOLISM, 2009, 10 (02) :99-109