Alterations in hepatocyte insulin binding in chronic pancreatitis

Effects of pancreatic polypeptide

Neal E. Seymour, Amy R. Volpert, Edward L. Lee, Dana Andersen, Carlos Hernandez

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Hepatic insulin resistance has previously been demonstrated in chronic pancreatitis, and has been shown to be ameliorated by pancreatic polypeptide administration. Insulin binding was investigated in chronic pancreatitis induced by infusion of oleic acid into the pancreatic duct of rats. Methods: Acute pancreatitis was induced in 12 200 to 225 g 8-weeek-old male Sprague-Dawley rats by intubation of the main bile duct at its junction with the duodenum through a small midline abdominal incision, and infusion of 99% oleic acid 0.015 mL/min for 4 minutes, with an additional 4 minutes dwell-time after infusion. Sham-operated animals served as controls. After 6 weeks, chronic pancreathic and sham-operated animals received either intraperitoneal bovine pancreatic polypeptide or saline vehicle for 5 days. Intraduodenal glucose tolerance tests (GIT) were performed in fasted animals, after which tissues were procured. Insulin receptors were isolated from solubilized hepatocyte and rectus abdominus membranes and competitive-binding studies were performed by incubation with 125I-insulin. Dissociation coefficients (Kd) and maximum binding capacities (Bmax) for high-affinity receptors were derived from Scatchard analyses. Results: Bmax and Kd in muscle were not altered in animals with chronic pancreatitis. In liver, Bmax was significantly less in rate with chronic pancreatitis given saline than in sham-operated rats given saline (17.0 ± 6.3 versus 47.6 ± 13.1 fmol/mg protein; data are mean ± SEM). Pancreatic polypeptide administration increased hepatic Bmax in rats with chronic pancreatitis (to 47.2 ± 9.8 fmol/mg protein), but had no significant effect in sham-operated rats. Receptor affinity was not significantly different in rats with chronic pancreatitis or rats who underwent sham operations and was unaltered by the administration of pancreatic polypeptide. The integrated plasma glucose response during the GTT was reduced by pancreatic polypeptide administration in rats with chronic pancreatitis (29.5 ± 15.0 mg/dL per minute versus 69.0 ± 21.8 in chronic pancreatitis without pancreatic polypeptide), but was not significantly altered in sham-operated animals. Conclusion: Diminished expression of highaffinity receptors on the hepatocyte membrane may contribute to hepatic insulin resistance in chronic pancreatitis. In this model, pancreatic polypeptide improved glucose tolerance and increased receptor capacity to the level observed in livers from nonpancreatitic animals.

Original languageEnglish (US)
Pages (from-to)105-110
Number of pages6
JournalThe American Journal of Surgery
Volume169
Issue number1
DOIs
StatePublished - 1995
Externally publishedYes

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Pancreatic Polypeptide
Chronic Pancreatitis
Hepatocytes
Insulin
Liver
Oleic Acid
Insulin Resistance
Glucose
Rectus Abdominis
Competitive Binding
Membranes
Pancreatic Ducts
Insulin Receptor
Glucose Tolerance Test
Bile Ducts
Duodenum
Intubation
Pancreatitis
Sprague Dawley Rats
Proteins

ASJC Scopus subject areas

  • Surgery

Cite this

Alterations in hepatocyte insulin binding in chronic pancreatitis : Effects of pancreatic polypeptide. / Seymour, Neal E.; Volpert, Amy R.; Lee, Edward L.; Andersen, Dana; Hernandez, Carlos.

In: The American Journal of Surgery, Vol. 169, No. 1, 1995, p. 105-110.

Research output: Contribution to journalArticle

Seymour, Neal E. ; Volpert, Amy R. ; Lee, Edward L. ; Andersen, Dana ; Hernandez, Carlos. / Alterations in hepatocyte insulin binding in chronic pancreatitis : Effects of pancreatic polypeptide. In: The American Journal of Surgery. 1995 ; Vol. 169, No. 1. pp. 105-110.
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abstract = "Background: Hepatic insulin resistance has previously been demonstrated in chronic pancreatitis, and has been shown to be ameliorated by pancreatic polypeptide administration. Insulin binding was investigated in chronic pancreatitis induced by infusion of oleic acid into the pancreatic duct of rats. Methods: Acute pancreatitis was induced in 12 200 to 225 g 8-weeek-old male Sprague-Dawley rats by intubation of the main bile duct at its junction with the duodenum through a small midline abdominal incision, and infusion of 99{\%} oleic acid 0.015 mL/min for 4 minutes, with an additional 4 minutes dwell-time after infusion. Sham-operated animals served as controls. After 6 weeks, chronic pancreathic and sham-operated animals received either intraperitoneal bovine pancreatic polypeptide or saline vehicle for 5 days. Intraduodenal glucose tolerance tests (GIT) were performed in fasted animals, after which tissues were procured. Insulin receptors were isolated from solubilized hepatocyte and rectus abdominus membranes and competitive-binding studies were performed by incubation with 125I-insulin. Dissociation coefficients (Kd) and maximum binding capacities (Bmax) for high-affinity receptors were derived from Scatchard analyses. Results: Bmax and Kd in muscle were not altered in animals with chronic pancreatitis. In liver, Bmax was significantly less in rate with chronic pancreatitis given saline than in sham-operated rats given saline (17.0 ± 6.3 versus 47.6 ± 13.1 fmol/mg protein; data are mean ± SEM). Pancreatic polypeptide administration increased hepatic Bmax in rats with chronic pancreatitis (to 47.2 ± 9.8 fmol/mg protein), but had no significant effect in sham-operated rats. Receptor affinity was not significantly different in rats with chronic pancreatitis or rats who underwent sham operations and was unaltered by the administration of pancreatic polypeptide. The integrated plasma glucose response during the GTT was reduced by pancreatic polypeptide administration in rats with chronic pancreatitis (29.5 ± 15.0 mg/dL per minute versus 69.0 ± 21.8 in chronic pancreatitis without pancreatic polypeptide), but was not significantly altered in sham-operated animals. Conclusion: Diminished expression of highaffinity receptors on the hepatocyte membrane may contribute to hepatic insulin resistance in chronic pancreatitis. In this model, pancreatic polypeptide improved glucose tolerance and increased receptor capacity to the level observed in livers from nonpancreatitic animals.",
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AU - Hernandez, Carlos

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