Abstract
IntroductionGlucose has been reported to have an essential role in the synthesis and secretion of insulin in hepatocytes. As the efflux of glucose is facilitated from the liver cells into the circulation, the mechanism of transportation of glucose into the hepatocytes for the synthesis of insulin was investigated. MethodsGrated liver suspension (GLS) was prepared by grating intact liver from adult mice by using a grater. Nitric oxide (NO) was measured by methemoglobin method. Glucose transporter-4 (Glut-4) was measured by immunoblot technique using Glut-4 antibody. ResultsIncubation of GLS with different amounts of glucose resulted in the uptake of glucose by the suspension with increased NO synthesis due to the stimulation of a glucose activated nitric oxide synthase that was present in the liver membrane. The inhibition of glucose induced NO synthesis resulted in the inhibition of glucose uptake. Glucose at 0.02M that maximally increased NO synthesis in the hepatocytes led to the translocation and increased synthesis of Glut-4 by 3.3 fold over the control that was inhibited by the inhibition of NO synthesis. The glucose induced NO synthesis was also found to result in the synthesis of insulin, in the presence of glucose due to the expression of both proinsulin genes I and II in the liver cells. ConclusionIt was concluded that glucose itself facilitated its own transportation in the liver cells both via Glut-4 and by the synthesis of NO which had an essential role for insulin synthesis in the presence of glucose in these cells.
Highlights
Glucose has been reported to have an essential role in the synthesis and secretion of insulin in hepatocytes
In the context that glucose was capable of stimulating the synthesis and secretion of insulin in the liver cells [3], similar to that in the pancreatic β cells [12], the influx of glucose from the circulation into the hepatic cells presented a potentially difficult problem because of the presence of Glut-2 in the liver cells that favours the efflux of glucose from the liver cells into the circulation for the maintenance of systemic glucose homeostasis to counteract the development of hypoglycaemia [13]
We report the existence of a novel constitutive form of nitric oxide synthase in the mice liver cell membrane that was found to be stimulated by glucose leading to the synthesis of Nitric oxide (NO) in the mice hepatocytes
Summary
Glucose has been reported to have an essential role in the synthesis and secretion of insulin in hepatocytes. A glucose transporter protein (MW 54Kda) known as glucose transporter- 4 (Glut-4) is reported to play a critically important role in the importation of the sugar into the hepatic cells from the external milieu through its translocation in the cell membrane both in the insulin dependent [10] and insulin independent processes [11]. The transportation of glucose in the liver cells as reported above was an insulin independent process [14], and, as such, the role of insulin itself for the translocation of Glut-4 to facilitate the influx of glucose into the liver cells in the presence of the opposing effect of Glut-2 in the hepatocytes remains obscure. Because the oxide had been reported before to facilitate the glucose transport into the pancreatic β cells [12]
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