In vitro isolated liver perfusion in a rat model of chronic pancreatitis (CP) has been shown to demonstrate hepatic resistance to insulin. The ability of pancreatic polypeptide (PP) to reverse the resistance to insulin on glucagon-stimulated hepatic glucose production was therefore investigated in this model. CP was induced in 250 to 300 gm Sprague-Dawley rats by infusion of 50 Al of 99% oleic acid into the pancreas via the common bile duct. After 6 to 8 weeks, isolated liver perfusion was performed on livers from both CP rats and sham-operated control animals (n = 12, 14), both with and without PP administration. Glucagon infusion (100 pg/ml for 30 minutes) produced a five- to sixfold increase in hepatic glucose production. The integrated hepatic glucose output (IHGO) response to glucagon alone was comparable in pancreatic and sham-operated animals; during period 1 (0 to 10 minutes) IHGO was 7.1 ± 0.5 mg/gm-min for sham-operated controls (n = 8) and 7.1 ± 0.4 mg/gm-min for pancreatitic animals (n = 6) without PP treatment. Animals that received PP (100 ng intraperitoneally 5 hours before liver harvest and perfusion with 4.2 ng/ml from 10 to 30 minutes) demonstrated an IHGO for period 1 for the sham (n = 6) and pancreatitic animals (n = 6) of 5.6 ± 0.6 and 4.8 ± 0.8 mg/gm-min, respectively. Insulin infusion (100 μU/ml added to perfusate from 10 to 30 minutes) in CP livers without PP revealed impaired responsiveness to insulin; the ratio of period 3 (20 to 30 minutes)/period 1 IHGO was 110% ± 5% in CP livers compared with 77% ± 5% in sham controls (p < 0.01). In contrast, PP treatment restored hepatic responsiveness to insulin to control levels; the period 3/period 1 IHGO was 75% ±13% in CP livers treated with PP, which was indistinguishable from the 67% ±9% response seen in sham-operated control animals. These data provide the first in vitro evidence of a primary hepatic glucoregulatory role of PP. Therefore PP deficiency may contribute to altered glucose metabolism through the induction of a reversible hepatic resistance to insulin.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Dec 1989|
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