In vitro hepatic insulin resistance in chronic pancreatitis in the rat

Neal E. Seymour, Jon B. Turk, Morris K. Laster, Yasuhiro Tanaka, Howard E. Rosenberg, Edward A. Rademaker, Alberto Pochettino, Dana K. Andersen

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17 Scopus citations


To investigate the effect of chronic pancreatitis (CP) on in vitro hepatic sensitivity to insulin, the suppression of glucagon-stimulated hepatic glucose production (HGP) by insulin was examined during isolated liver perfusion (ILP) in CP and sham-operated rats. CP was induced at laparotomy by infusion of 50 μl 99% oleic acid into the common bile duct during temporary occlusion of the proximal hepatic duct in 250- to 350-g Sprague-Dawley rats. Eight to sixteen weeks later, single-pass ILP was performed on fed animals. Glucagon (100 pg/ml) was infused for 30 min; the final 20 min of perfusion was performed with (a) no insulin, (b) 25 μ/ml insulin, or (c) 100 μU/ml insulin. CP and sham rats demonstrated comparable HGP responses to glucagon during the 0- to 10-min period (5.2 ± 0.5 vs 5.9 ± 0.5 mg/g/min, P = NS). CP rats demonstrated an HGP response to glucagon alone more evanescent than that in sham rats (20-30 min of HGP, 6.6 ± 0.6 vs 9.5 ± 0.4 mg/g/min, P < 0.05). Sham rats showed a dose-dependent inhibition of HGP by insulin, however (percentage 20-30 min of HGP/0-10 min of HGP for 0, 25, and 100 μU/ml insulin: 166 ± 12, 125 ± 7, and 101 ± 5%, P < 0.01), whereas CP rats showed no effect of insulin (130 ± 6, 123 ± 7, 134 ± 7%, P = NS). Pre- and postperfusion liver glycogen contents revealed comparable decreases in liver glycogen in both groups: insulin inhibition of HGP in sham rats was accompanied by higher postperfusion glycogen content. These data demonstrate a loss of insulin-mediated suppression of hepatic glucose production in livers obtained from pancreatitic rats. We conclude that CP is accompanied by a primary hepatic resistance to insulin; this defect may play a role in the etiology of pancreatogenic diabetes.

Original languageEnglish (US)
Pages (from-to)450-456
Number of pages7
JournalJournal of Surgical Research
Issue number5
StatePublished - May 1989
Externally publishedYes

ASJC Scopus subject areas

  • Surgery


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