Insulin regulation of hepatic glucose transporter protein is impaired in chronic pancreatitis

Dana Andersen, Catherine L. Ruiz, Charles F. Burant

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Objective: The effect of chronic pancreatitis and insulin on the expression of the hepatic facilitative glucose transporter protein (GLUT-2) was determined in rats. Summary Background Data: Chronic pancreatitis is associated with diabetes mellitus or impaired glucose tolerance. Suppression of hepatic glucose production (HGP) by insulin is impaired, although the mechanism is unknown. Methods: Normal rats, rats with chronic pancreatitis induced 12 to 16 weeks earlier by oleic acid injection into the pancreatic ducts, and sham-operated rats were studied. Isolated, single-pass liver perfusion was performed, during which glucagon (1.2 pM) was infused, with or without insulin (0.6 or 1.2 nM). The suppression of HGP production by insulin was compared with changes in GLUT-2 in the membrane fraction of liver biopsies obtained before and after hormone perfusion. Results: Glycogen-rich (fed) livers of normal rats (n = 16) demonstrated a dose-dependent suppression of hepatic glucose production by insulin (50 ± 5% HGP induced by glucagon alone during 1.2-nM insulin perfusion) and a dose-dependent decrease in GLUT-2 (30 ± 13% of basal level during 1.2-nM insulin perfusion). Sham- operated rats (n = 6) also showed reductions in HGP (51 ± 4%) and GLUT-2 (14 ± 10%) during 1.2-nM insulin perfusion. In contrast, rats with chronic pancreatitis (n = 6) showed no suppression of HGP during 1.2-nM insulin perfusion, and an increase in GLUT-2 (+20 ± 6%) after insulin perfusion (p <0.02 vs. sham). Conclusions: Insulin suppresses glucagon-stimulated HGP in normal and sham-operated rats, and this reduction in HGP is associated with a decrease in the membrane-bound quantity of GLUT-2. In chronic pancreatitis, insulin suppression of HGP is absent, and this is accompanied by an increase in GLUT-2 in the hepatocyte membrane. The authors conclude that the insulin- mediated change in the level of hepatocyte GLUT-2 is impaired in chronic pancreatitis, and may contribute to the altered glucose metabolism observed commonly in this disease.

Original languageEnglish (US)
Pages (from-to)679-687
Number of pages9
JournalAnnals of Surgery
Volume219
Issue number6
StatePublished - Jun 1994
Externally publishedYes

Fingerprint

Facilitative Glucose Transport Proteins
Chronic Pancreatitis
Insulin
Liver
Glucose
Perfusion
Proteins
Glucagon
Membranes
Glucose Transporter Type 2
Hepatocytes
Glucose Intolerance
Pancreatic Ducts
Oleic Acid
Glycogen
Diabetes Mellitus

ASJC Scopus subject areas

  • Surgery

Cite this

Insulin regulation of hepatic glucose transporter protein is impaired in chronic pancreatitis. / Andersen, Dana; Ruiz, Catherine L.; Burant, Charles F.

In: Annals of Surgery, Vol. 219, No. 6, 06.1994, p. 679-687.

Research output: Contribution to journalArticle

Andersen, Dana ; Ruiz, Catherine L. ; Burant, Charles F. / Insulin regulation of hepatic glucose transporter protein is impaired in chronic pancreatitis. In: Annals of Surgery. 1994 ; Vol. 219, No. 6. pp. 679-687.
@article{8ebdc3fc0a304edcbcf578bb8212c910,
title = "Insulin regulation of hepatic glucose transporter protein is impaired in chronic pancreatitis",
abstract = "Objective: The effect of chronic pancreatitis and insulin on the expression of the hepatic facilitative glucose transporter protein (GLUT-2) was determined in rats. Summary Background Data: Chronic pancreatitis is associated with diabetes mellitus or impaired glucose tolerance. Suppression of hepatic glucose production (HGP) by insulin is impaired, although the mechanism is unknown. Methods: Normal rats, rats with chronic pancreatitis induced 12 to 16 weeks earlier by oleic acid injection into the pancreatic ducts, and sham-operated rats were studied. Isolated, single-pass liver perfusion was performed, during which glucagon (1.2 pM) was infused, with or without insulin (0.6 or 1.2 nM). The suppression of HGP production by insulin was compared with changes in GLUT-2 in the membrane fraction of liver biopsies obtained before and after hormone perfusion. Results: Glycogen-rich (fed) livers of normal rats (n = 16) demonstrated a dose-dependent suppression of hepatic glucose production by insulin (50 ± 5{\%} HGP induced by glucagon alone during 1.2-nM insulin perfusion) and a dose-dependent decrease in GLUT-2 (30 ± 13{\%} of basal level during 1.2-nM insulin perfusion). Sham- operated rats (n = 6) also showed reductions in HGP (51 ± 4{\%}) and GLUT-2 (14 ± 10{\%}) during 1.2-nM insulin perfusion. In contrast, rats with chronic pancreatitis (n = 6) showed no suppression of HGP during 1.2-nM insulin perfusion, and an increase in GLUT-2 (+20 ± 6{\%}) after insulin perfusion (p <0.02 vs. sham). Conclusions: Insulin suppresses glucagon-stimulated HGP in normal and sham-operated rats, and this reduction in HGP is associated with a decrease in the membrane-bound quantity of GLUT-2. In chronic pancreatitis, insulin suppression of HGP is absent, and this is accompanied by an increase in GLUT-2 in the hepatocyte membrane. The authors conclude that the insulin- mediated change in the level of hepatocyte GLUT-2 is impaired in chronic pancreatitis, and may contribute to the altered glucose metabolism observed commonly in this disease.",
author = "Dana Andersen and Ruiz, {Catherine L.} and Burant, {Charles F.}",
year = "1994",
month = "6",
language = "English (US)",
volume = "219",
pages = "679--687",
journal = "Annals of Surgery",
issn = "0003-4932",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Insulin regulation of hepatic glucose transporter protein is impaired in chronic pancreatitis

AU - Andersen, Dana

AU - Ruiz, Catherine L.

AU - Burant, Charles F.

PY - 1994/6

Y1 - 1994/6

N2 - Objective: The effect of chronic pancreatitis and insulin on the expression of the hepatic facilitative glucose transporter protein (GLUT-2) was determined in rats. Summary Background Data: Chronic pancreatitis is associated with diabetes mellitus or impaired glucose tolerance. Suppression of hepatic glucose production (HGP) by insulin is impaired, although the mechanism is unknown. Methods: Normal rats, rats with chronic pancreatitis induced 12 to 16 weeks earlier by oleic acid injection into the pancreatic ducts, and sham-operated rats were studied. Isolated, single-pass liver perfusion was performed, during which glucagon (1.2 pM) was infused, with or without insulin (0.6 or 1.2 nM). The suppression of HGP production by insulin was compared with changes in GLUT-2 in the membrane fraction of liver biopsies obtained before and after hormone perfusion. Results: Glycogen-rich (fed) livers of normal rats (n = 16) demonstrated a dose-dependent suppression of hepatic glucose production by insulin (50 ± 5% HGP induced by glucagon alone during 1.2-nM insulin perfusion) and a dose-dependent decrease in GLUT-2 (30 ± 13% of basal level during 1.2-nM insulin perfusion). Sham- operated rats (n = 6) also showed reductions in HGP (51 ± 4%) and GLUT-2 (14 ± 10%) during 1.2-nM insulin perfusion. In contrast, rats with chronic pancreatitis (n = 6) showed no suppression of HGP during 1.2-nM insulin perfusion, and an increase in GLUT-2 (+20 ± 6%) after insulin perfusion (p <0.02 vs. sham). Conclusions: Insulin suppresses glucagon-stimulated HGP in normal and sham-operated rats, and this reduction in HGP is associated with a decrease in the membrane-bound quantity of GLUT-2. In chronic pancreatitis, insulin suppression of HGP is absent, and this is accompanied by an increase in GLUT-2 in the hepatocyte membrane. The authors conclude that the insulin- mediated change in the level of hepatocyte GLUT-2 is impaired in chronic pancreatitis, and may contribute to the altered glucose metabolism observed commonly in this disease.

AB - Objective: The effect of chronic pancreatitis and insulin on the expression of the hepatic facilitative glucose transporter protein (GLUT-2) was determined in rats. Summary Background Data: Chronic pancreatitis is associated with diabetes mellitus or impaired glucose tolerance. Suppression of hepatic glucose production (HGP) by insulin is impaired, although the mechanism is unknown. Methods: Normal rats, rats with chronic pancreatitis induced 12 to 16 weeks earlier by oleic acid injection into the pancreatic ducts, and sham-operated rats were studied. Isolated, single-pass liver perfusion was performed, during which glucagon (1.2 pM) was infused, with or without insulin (0.6 or 1.2 nM). The suppression of HGP production by insulin was compared with changes in GLUT-2 in the membrane fraction of liver biopsies obtained before and after hormone perfusion. Results: Glycogen-rich (fed) livers of normal rats (n = 16) demonstrated a dose-dependent suppression of hepatic glucose production by insulin (50 ± 5% HGP induced by glucagon alone during 1.2-nM insulin perfusion) and a dose-dependent decrease in GLUT-2 (30 ± 13% of basal level during 1.2-nM insulin perfusion). Sham- operated rats (n = 6) also showed reductions in HGP (51 ± 4%) and GLUT-2 (14 ± 10%) during 1.2-nM insulin perfusion. In contrast, rats with chronic pancreatitis (n = 6) showed no suppression of HGP during 1.2-nM insulin perfusion, and an increase in GLUT-2 (+20 ± 6%) after insulin perfusion (p <0.02 vs. sham). Conclusions: Insulin suppresses glucagon-stimulated HGP in normal and sham-operated rats, and this reduction in HGP is associated with a decrease in the membrane-bound quantity of GLUT-2. In chronic pancreatitis, insulin suppression of HGP is absent, and this is accompanied by an increase in GLUT-2 in the hepatocyte membrane. The authors conclude that the insulin- mediated change in the level of hepatocyte GLUT-2 is impaired in chronic pancreatitis, and may contribute to the altered glucose metabolism observed commonly in this disease.

UR - http://www.scopus.com/inward/record.url?scp=0028260734&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028260734&partnerID=8YFLogxK

M3 - Article

VL - 219

SP - 679

EP - 687

JO - Annals of Surgery

JF - Annals of Surgery

SN - 0003-4932

IS - 6

ER -