Isolated hepatic cholinergic denervation impairs glucose and glycogen metabolism

Chengrui Xue, Gudrun Aspelund, Kumudesh C. Sritharan, Jin Ping Wang, Lori A. Slezak, Dana Andersen

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Background. Hepatic innervation plays an essential role in insulin extraction and glucose production, but the specific role of hepatic cholinergic innervation remains unclear. We sought to establish a model of isolated hepatic cholinergic denervation (IHCD), and to assess whether glycogen storage or the control of net hepatic glucose production (HGP) was altered by IHCD. Materials and Methods. Sprague-Dawley rats underwent either hepatic vagotomy or sham operation. Liver tissue was stained for vesicular acetylcholine transporter (VAChT) and (nonspecific neural) protein gene product 9.5 (PGP) for verification of IHCD. Liver glycogen content was quantified in fed and fasted IHCD or sham-operated animals. HGP was determined after single-pass isolated liver perfusion, during which a 30-rain 12 ng/ml glucagon infusion was begun after equilibration, and after 10 min, a 200 μU/ml insulin infusion was added. Results. Uniform staining of PGP and absence of VAChT staining in hepatic vagotomized rats demonstrated the validity of our model. Glycogen content of sham-operated livers (n = 8) increased from 6.0 ± 1.7 in the tasting state to 10.6 ± 1.8 mg/g liver, after feeding (P <0.05). IHCD livers (n = 8) showed no comparable increase (3.5 ± 0.6 to 4.0 ± 0.7 mg/g liver). Perfusion with glucagon alone resulted in less HGP in IHCD livers (n = 12) compared with sham-operated livers (n = 10) (integrated HGP 3.3 ± 0.3 mg/g liver rain-1 vs 5.1 ± 0.5 mg/g liver rain-1, P <0.05). Insulin infusion revealed impaired responsiveness to insulin after IHCD; the ratio of HGP in the final 10 min of perfusion (glucagon and insulin) to HGP in the initial 10 rain (glucagon alone) was 90.3 ± 2.4% for IHCD livers versus 68.1 ± 4.4% for sham-operated controls, respectively (P = 0.0002). Conclusions. Our study shows that IHCD results in significant impairment in liver glycogen storage and impaired hepatic sensitivity to glucagon and, possibly, to insulin. We conclude that hepatic cholinergic integrity is essential to normal hepatic glucose metabolism. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)19-25
Number of pages7
JournalJournal of Surgical Research
Volume90
Issue number1
DOIs
StatePublished - May 1 2000
Externally publishedYes

Fingerprint

Denervation
Glycogen
Cholinergic Agents
Glucose
Liver
Glucagon
Rain
Insulin
Vesicular Acetylcholine Transport Proteins
Liver Glycogen
Perfusion

Keywords

  • Animal
  • Cholinergic denervation
  • Glucose and glycogen metabolism
  • Hepatic vagotomy
  • Insulin and glucagon sensitivity
  • Isolated liver per fusion
  • Rat

ASJC Scopus subject areas

  • Surgery

Cite this

Isolated hepatic cholinergic denervation impairs glucose and glycogen metabolism. / Xue, Chengrui; Aspelund, Gudrun; Sritharan, Kumudesh C.; Wang, Jin Ping; Slezak, Lori A.; Andersen, Dana.

In: Journal of Surgical Research, Vol. 90, No. 1, 01.05.2000, p. 19-25.

Research output: Contribution to journalArticle

Xue, Chengrui ; Aspelund, Gudrun ; Sritharan, Kumudesh C. ; Wang, Jin Ping ; Slezak, Lori A. ; Andersen, Dana. / Isolated hepatic cholinergic denervation impairs glucose and glycogen metabolism. In: Journal of Surgical Research. 2000 ; Vol. 90, No. 1. pp. 19-25.
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title = "Isolated hepatic cholinergic denervation impairs glucose and glycogen metabolism",
abstract = "Background. Hepatic innervation plays an essential role in insulin extraction and glucose production, but the specific role of hepatic cholinergic innervation remains unclear. We sought to establish a model of isolated hepatic cholinergic denervation (IHCD), and to assess whether glycogen storage or the control of net hepatic glucose production (HGP) was altered by IHCD. Materials and Methods. Sprague-Dawley rats underwent either hepatic vagotomy or sham operation. Liver tissue was stained for vesicular acetylcholine transporter (VAChT) and (nonspecific neural) protein gene product 9.5 (PGP) for verification of IHCD. Liver glycogen content was quantified in fed and fasted IHCD or sham-operated animals. HGP was determined after single-pass isolated liver perfusion, during which a 30-rain 12 ng/ml glucagon infusion was begun after equilibration, and after 10 min, a 200 μU/ml insulin infusion was added. Results. Uniform staining of PGP and absence of VAChT staining in hepatic vagotomized rats demonstrated the validity of our model. Glycogen content of sham-operated livers (n = 8) increased from 6.0 ± 1.7 in the tasting state to 10.6 ± 1.8 mg/g liver, after feeding (P <0.05). IHCD livers (n = 8) showed no comparable increase (3.5 ± 0.6 to 4.0 ± 0.7 mg/g liver). Perfusion with glucagon alone resulted in less HGP in IHCD livers (n = 12) compared with sham-operated livers (n = 10) (integrated HGP 3.3 ± 0.3 mg/g liver rain-1 vs 5.1 ± 0.5 mg/g liver rain-1, P <0.05). Insulin infusion revealed impaired responsiveness to insulin after IHCD; the ratio of HGP in the final 10 min of perfusion (glucagon and insulin) to HGP in the initial 10 rain (glucagon alone) was 90.3 ± 2.4{\%} for IHCD livers versus 68.1 ± 4.4{\%} for sham-operated controls, respectively (P = 0.0002). Conclusions. Our study shows that IHCD results in significant impairment in liver glycogen storage and impaired hepatic sensitivity to glucagon and, possibly, to insulin. We conclude that hepatic cholinergic integrity is essential to normal hepatic glucose metabolism. (C) 2000 Academic Press.",
keywords = "Animal, Cholinergic denervation, Glucose and glycogen metabolism, Hepatic vagotomy, Insulin and glucagon sensitivity, Isolated liver per fusion, Rat",
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AU - Aspelund, Gudrun

AU - Sritharan, Kumudesh C.

AU - Wang, Jin Ping

AU - Slezak, Lori A.

AU - Andersen, Dana

PY - 2000/5/1

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N2 - Background. Hepatic innervation plays an essential role in insulin extraction and glucose production, but the specific role of hepatic cholinergic innervation remains unclear. We sought to establish a model of isolated hepatic cholinergic denervation (IHCD), and to assess whether glycogen storage or the control of net hepatic glucose production (HGP) was altered by IHCD. Materials and Methods. Sprague-Dawley rats underwent either hepatic vagotomy or sham operation. Liver tissue was stained for vesicular acetylcholine transporter (VAChT) and (nonspecific neural) protein gene product 9.5 (PGP) for verification of IHCD. Liver glycogen content was quantified in fed and fasted IHCD or sham-operated animals. HGP was determined after single-pass isolated liver perfusion, during which a 30-rain 12 ng/ml glucagon infusion was begun after equilibration, and after 10 min, a 200 μU/ml insulin infusion was added. Results. Uniform staining of PGP and absence of VAChT staining in hepatic vagotomized rats demonstrated the validity of our model. Glycogen content of sham-operated livers (n = 8) increased from 6.0 ± 1.7 in the tasting state to 10.6 ± 1.8 mg/g liver, after feeding (P <0.05). IHCD livers (n = 8) showed no comparable increase (3.5 ± 0.6 to 4.0 ± 0.7 mg/g liver). Perfusion with glucagon alone resulted in less HGP in IHCD livers (n = 12) compared with sham-operated livers (n = 10) (integrated HGP 3.3 ± 0.3 mg/g liver rain-1 vs 5.1 ± 0.5 mg/g liver rain-1, P <0.05). Insulin infusion revealed impaired responsiveness to insulin after IHCD; the ratio of HGP in the final 10 min of perfusion (glucagon and insulin) to HGP in the initial 10 rain (glucagon alone) was 90.3 ± 2.4% for IHCD livers versus 68.1 ± 4.4% for sham-operated controls, respectively (P = 0.0002). Conclusions. Our study shows that IHCD results in significant impairment in liver glycogen storage and impaired hepatic sensitivity to glucagon and, possibly, to insulin. We conclude that hepatic cholinergic integrity is essential to normal hepatic glucose metabolism. (C) 2000 Academic Press.

AB - Background. Hepatic innervation plays an essential role in insulin extraction and glucose production, but the specific role of hepatic cholinergic innervation remains unclear. We sought to establish a model of isolated hepatic cholinergic denervation (IHCD), and to assess whether glycogen storage or the control of net hepatic glucose production (HGP) was altered by IHCD. Materials and Methods. Sprague-Dawley rats underwent either hepatic vagotomy or sham operation. Liver tissue was stained for vesicular acetylcholine transporter (VAChT) and (nonspecific neural) protein gene product 9.5 (PGP) for verification of IHCD. Liver glycogen content was quantified in fed and fasted IHCD or sham-operated animals. HGP was determined after single-pass isolated liver perfusion, during which a 30-rain 12 ng/ml glucagon infusion was begun after equilibration, and after 10 min, a 200 μU/ml insulin infusion was added. Results. Uniform staining of PGP and absence of VAChT staining in hepatic vagotomized rats demonstrated the validity of our model. Glycogen content of sham-operated livers (n = 8) increased from 6.0 ± 1.7 in the tasting state to 10.6 ± 1.8 mg/g liver, after feeding (P <0.05). IHCD livers (n = 8) showed no comparable increase (3.5 ± 0.6 to 4.0 ± 0.7 mg/g liver). Perfusion with glucagon alone resulted in less HGP in IHCD livers (n = 12) compared with sham-operated livers (n = 10) (integrated HGP 3.3 ± 0.3 mg/g liver rain-1 vs 5.1 ± 0.5 mg/g liver rain-1, P <0.05). Insulin infusion revealed impaired responsiveness to insulin after IHCD; the ratio of HGP in the final 10 min of perfusion (glucagon and insulin) to HGP in the initial 10 rain (glucagon alone) was 90.3 ± 2.4% for IHCD livers versus 68.1 ± 4.4% for sham-operated controls, respectively (P = 0.0002). Conclusions. Our study shows that IHCD results in significant impairment in liver glycogen storage and impaired hepatic sensitivity to glucagon and, possibly, to insulin. We conclude that hepatic cholinergic integrity is essential to normal hepatic glucose metabolism. (C) 2000 Academic Press.

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