In vitro hepatic insulin resistance in chronic pancreatitis in the rat.
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 microliters 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 microU/ml insulin, or (c) 100 microU/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 less than 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 microU/ml insulin: 166 +/- 12, 125 +/- 7, and 101 +/- 5%, P less than 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.
Seymour
N E
NE
Department of Surgery, State University of New York Health Science Center, Brooklyn 11203.
Turk
J B
JB
Laster
M K
MK
Tanaka
Y
Y
Rosenberg
H E
HE
Rademaker
E A
EA
Pochettino
A
A
Andersen
D K
DK
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002908:Chronic Disease; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000032:analysis; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000032:analysis / Q000378:metabolism*; D008297:Male; D010195:Pancreatitis / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D006003:Glycogen; D005934:Glucagon; D005947:Glucose