Regulation of net hepatic glucose uptake: interaction of neural and pancreatic mechanisms

Abstract

Summary ― Insulin and glucagon levels, the mass of glucose presented to the liver and the portal signal are important regulators of the liver's response to glucose delivery. The portal signal not only serves to direct glucose into the liver but also appears to stimulate its deposition in glycogen. Moreover, the portal signal impacts on tissues other than the liver: intraportal glucose delivery is associated with changes in glucose uptake by nonhepatic tissues and neurally-mediated enhancement of pancreatic insulin secretion. Our current understanding of the neural control of hepatic glucose metabolism includes a tonic block to the entry of glucose into the liver, probably mediated both by sympathetic neural activity and by a low insulin:glucagon ratio. An increase in the portal vein glucose level is detected by sensors in the portal region, which cause a decrease in the firing rate in the afferent fibers in the hepatic branch of the vagus nerve. The change in the afferent firing rate is processed in the hypothalamus and instigates a change in the efferent firing rate in the hepatic and pancreatic branches of the vagus (with corresponding increases in insulin secretion and net hepatic glucose uptake). The

A free-choice high-fat high-sugar diet induces glucose intolerance and insulin unresponsiveness to a glucose load not explained by obesity

“…The pancreas is innervated by the ANS and it has been shown that the hypothalamus may regulate this sensitivity via this ANS innervation. [25][26][27][28] The latter hypothesis is supported by our recent finding that centrally, neuropeptide Y and proopiomelanocortin mRNA expression in the arcuate nucleus were altered in HFHS-choice diet rats in such a direction that it promotes glucose intolerance and insulin resistance. 15 Neuropeptide Y-and proopiomelanocortinexpressing neurons in the arcuate nucleus affect glucose metabolism via their projections to (pre-autonomic) hypothalamic neurons that control the autonomic nervous input to various peripheral organs, such as the pancreas.…”

Impaired Glucose Homeostasis in Mice Lacking the α1b-Adrenergic Receptor Subtype

“…8). This could be due to several factors including the absence of the ␣ 1b -AR-mediated glycogenolysis, the increased insulinemia in the postabsorptive state in face of normal glucagon levels, the increased parasympathetic nervous activity, which stimulates glycogen synthesis (7,(43)(44)(45)(46) or a combination of them. Strikingly, the rate of glycogen degradation was similar in control and mutant mice during the initial fed to fasted transition or following an intraperitoneal glucagon injection (Fig.…”

Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats

“…However, the present results strongly suggest that the CSMG plays a pivotal role in hepatic glucose metabolism. In previous studies, the electrical stimulation of either VMH or peripheral splanchnic nerves increased in the activity of hepatic glycogen phosphorylase [12][13][14]. Proost C et al have reported in rabbit study that the activation of glycogen phosphorylase (phosphorylase α) was increased by electrical stimulation of splanchnic nerve.…”