Involvement of the vagus nerves in the regulation of basal hepatic glucose production in conscious dogs

Abstract

. Involvement of the vagus nerves in the regulation of basal hepatic glucose production in conscious dogs. Am J Physiol Endocrinol Metab 283: E958-E964, 2002; 10.1152/ajpendo.00566. 2001.-We determined if blocking transmission in the fibers of the vagus nerves would affect basal hepatic glucose metabolism in the 18-h-fasted conscious dog. A pancreatic clamp (somatostatin, basal portal insulin, and glucagon) was employed. A 40-min control period was followed by a 90-min test period. In one group, stainless steel cooling coils (Sham, n ϭ 5) were perfused with a 37°C solution, while in the other (Cool, n ϭ 6), the coils were perfused with Ϫ20°C solution. Vagal blockade was verified by heart rate change (80 Ϯ 9 to 84 Ϯ 14 beats/min in Sham; 98 Ϯ 12 to 193 Ϯ 22 beats/min in Cool). The arterial glucose level was kept euglycemic by glucose infusion. No change in tracer-determined glucose production occurred in Sham, whereas in Cool it dropped significantly (2.4 Ϯ 0.4 to 1.9 Ϯ 0.4 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ). Net hepatic glucose output did not change in Sham but decreased from 1.9 Ϯ 0.3 to 1.3 Ϯ 0.3 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 in the Cool group. Hepatic gluconeogenesis did not change in either group. These data suggest that vagal blockade acutely modulates hepatic glucose production by inhibiting glycogenolysis. vagal cooling; liver nerves; parasympathetic blockade; gluconeogenesis; glycogenolysis THE AUTONOMIC NERVOUS SYSTEM is involved in the regulation of hepatic glucose metabolism. It has been demonstrated, for example, that electrical stimulation of the vagus nerves induces activation of the liver enzyme glycogen synthase, which in turn increases glycogen synthesis and reduces glucose output (19). Conversely, electrical stimulation of the splanchnic nerve induces activation of the liver enzyme glycogen phosphorylase, which in turn increases glycogenolysis and glucose output (20). Taken together, these data have been interpreted to suggest that activation of the parasympathetic nervous system promotes glucose uptake and hepatic glycogen deposition while activation of the sympathetic nervous system promotes glycogenolysis and glucose output.It is also known that glucosensors within the hepatoportal region have the ability to sense glucose and inform the brain of its concentration via afferent fibers traveling, at least in part, along the hepatic vagus nerves (16). It has been hypothesized that the brain uses this information to minimize fluctuations in the plasma glucose level after feeding (18). The efferent responses of this feedback loop involve the pancreas, adrenal glands, adipocytes, skeletal muscles, and the liver (2). Although it is known that the autonomic nervous system is vital to the regulation of glucose metabolism in times of stress, evidence is accumulating to support a role for it in the postprandial state. Nevertheless, its role in regulating hepatic glucose metabolism after an overnight fast is not clear.Our aim, therefore, was to cool the vagus nerves, in the presence of a pancreatic clamp, to study the involve...

Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal

“…Thus we conclude that the sympathetic efferents play an important role in the regulation of NHGU by exerting a basal inhibitory tone that limits glucose uptake in response to hyperglycemia of peripheral origin. This is consistent with previous work from our laboratory (8), which showed that cooling the vagus nerves (decreasing afferent vagal firing) in the presence of euglycemia and euinsulinemia decreased net hepatic glucose output, presumably by reflexively decreasing the efferent sympathetic outflow to the liver. It is interesting to note that we saw no differences in basal net hepatic glucose output between the two groups in this current study despite hepatic denervation.…”

“…Although extensive research has been carried out relating to hepatic afferents and efferents in the euglycemic and hypoglycemic states (8,16,21,22,24,26,34), less is known about the hyperglycemic state, and it remains unclear how the portal signal may be mediated by these nerves. Total hepatic denervation eliminates the ability of the liver to discriminate between portal and peripheral glucose delivery (3), reinforcing the notion that the response to the portal glucose signal is neurally mediated (32,36).…”

Sixteen years and counting: an update on leptin in energy balance

“…At least in mice, these effects can be largely independent of modifications in feeding and body weight. Based on the known importance of the parasympathetic outflow to the liver in regulating glucose production in several different species (56,57), it has been hypothesized that the vagus nerve is an important efferent arm of the nervous system mediating the antidiabetic actions of leptin. For example, the effects of leptin…”

The effect of vagal cooling on canine hepatic glucose metabolism in the presence of hyperglycemia of peripheral origin

“…Although extensive research has been carried out relating to hepatic afferents and efferents in the euglycemic and hypoglycemic states [18][19][20][21][22][23][24], less is known about them in the hyperglycemic state. Furthermore, it remains unclear how they are involved in the augmentation of NHGU by portal glucose delivery.…”