TY - JOUR
T1 - In vitro hepatic insulin resistance in chronic pancreatitis in the rat
AU - Seymour, Neal E.
AU - Turk, Jon B.
AU - Laster, Morris K.
AU - Tanaka, Yasuhiro
AU - Rosenberg, Howard E.
AU - Rademaker, Edward A.
AU - Pochettino, Alberto
AU - Andersen, Dana K.
N1 - Funding Information:
This research was supported by a grant from the Foundation gical Education and Investigation, Inc.
PY - 1989/5
Y1 - 1989/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0024392171&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024392171&partnerID=8YFLogxK
U2 - 10.1016/0022-4804(89)90159-5
DO - 10.1016/0022-4804(89)90159-5
M3 - Article
C2 - 2654478
AN - SCOPUS:0024392171
SN - 0022-4804
VL - 46
SP - 450
EP - 456
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 5
ER -