title: The activation by glucose of liver membrane nitric oxide synthase in the synthesis and translocation of glucose transporter-4 in the production of insulin in the mice hepatocytes.
abstract: BACKGROUND
  Glucose 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.
  
  
  METHODS
  Grated 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.
  
  
  RESULTS
  Incubation 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.
  
  
  CONCLUSIONS
  It 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.
authors.affiliation: Department of Biochemistry, Sinha Institute of Medical Science and Technology, Kolkata, India ; Department of Biochemistry, Vidyasagar University, Midnapore, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Department of Biochemistry, Sinha Institute of Medical Science and Technology, Kolkata, India.
authors.forename: Rajeshwary
authors.initials: R
authors.lastname: Ghosh
authors.affiliation: Department of Biochemistry, Vidyasagar University, Midnapore, India.
authors.forename: Smarajit
authors.initials: S
authors.lastname: Maiti
authors.affiliation: Department of Biochemistry, Sinha Institute of Medical Science and Technology, Kolkata, India.
authors.forename: Gausal Azam
authors.initials: GA
authors.lastname: Khan
authors.affiliation: Department of Biochemistry, Sinha Institute of Medical Science and Technology, Kolkata, India.
authors.forename: Asru K
authors.initials: AK
authors.lastname: Sinha
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis* / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D011384:Proinsulin / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D020033:Protein Isoforms; C495693:Slc2a4 protein, mouse; D009569:Nitric Oxide; D011384:Proinsulin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D005947:Glucose