Hypothalamus–Brain Stem Circuitry Responsible for Vagal Efferent Signaling to the Pancreas Evoked By Hypoglycemia in Rat
Authors: Chung Owyang
Xiaoyin Wu
Jun Gao
Jin Yan
Ying Li
Journal: Journal of Neurophysiology (2004)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: glucose levels; vagal neural activity; pancreatic functions; hypoglycemia; neurotransmitters
Affiliations: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.

Abstract:  Circulating glucose levels significantly affect vagal neural activity, which is important in the regulation of pancreatic functions. Little is known about the mechanisms involved. This study investigates the neural pathways responsible for hypoglycemia-induced vagal efferent signaling to the pancreas and identifies the neurotransmitters involved. Vagal pancreatic efferent nerve activities were recorded in anesthetized rats. Insulin-induced hypoglycemia, a decrease of blood glucose levels from 114 +/- 5 to 74 +/- 6 mg dl(-1), stimulated an increase in pancreatic efferent nerve firing from a basal rate of 1.1 +/- 0.3 to 19 +/- 3 impulses 30 s(-1). In contrast, vagal primary afferent neuronal discharges recorded in the nodose ganglia were unaltered by systemic hypoglycemia. Vagal afferent rootlet section plus splanchnicotomy had no effect on hypoglycemia-induced vagal efferent firing, suggesting a central site of action. Decerebration reduced the increase in nerve firing stimulated by hypoglycemia from 21 +/- 4 to 9.6 +/- 2 impulses 30 s(-1). Chemical ablation of the lateral hypothalamic area, but not the arcuate nucleus, inhibited pancreatic nerve firing evoked by hypoglycemia. Microinjection of the orexin-A receptor antagonist SB-334867 into the dorsal motor nucleus of the vagus (DMV) inhibited pancreatic nerve firing evoked by insulin-induced hypoglycemia by 56%. In contrast, injection of orexin-A (20 pmol) into the DMV elicited a 30-fold increase in pancreatic nerve firing. We concluded that systemic hypoglycemia stimulates pancreatic efferent nerve firing through a central mechanism. Full expression of pancreatic nerve activities during hypoglycemia requires both the forebrain and the brain stem. In addition to activating neurons in the brain stem, central neuroglucopenia activates subpopulations of neurons in the lateral hypothalamic area that contain orexin. The released orexin acts on DMV neurons to stimulate pancreatic efferent nerve activities and thus regulate pancreatic functions. 

Retracted: No

PubPeer comments:
 The trace in Fig 2A repeats itself. ![file] , 
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 2B, 2C: ![file] Here s 2C, superimposed on 2B to show how many spikes they share in common. ![file] , 
 Fig 5C. I am lost for words. ![file] , 
 Fig 10 A, B. Basically the same, apart from the addition of different patterns of spikes. ![file] , 
 Figure 12 has been neglected. ![file] , 
 Figure 9. This image has several unusual features. First, anyone who has done NPY immunohistochemistry in the brain knows that NPY accumulates preferentially in fibers rather than cell bodies. Second, NPY cells in this region normally seat tightly packed together. Finally, many cells are surprisingly similar, even thought not strictly identical due to the low resolution of the published image.![file] ,