Effective portal insulin delivery with enzyme-protected capsules in pancreatectomized pigs.
1. Plasma concentrations of insulin, C-peptide, glucagon and glucose were measured in surgically pancreatectomized pigs given insulin into the colon directly and in enteric peptidase-resistant (methacrylic acid copolymer-encapsulated) form. 2. Following introduction of insulin-containing capsules, plasma insulin concentration rose from 2.7 +/- 0.1 microU/ml to 110.9 +/- 51.9 microU/ml in the portal vein, and from 2.6 +/- 0.1 microU/ml to 26.9 +/- 7.3 microU/ml in the systemic circulation. Corresponding portal and systemic values after direct (non-encapsulated) insulin instillation were 28.2 +/- 15.9 microU/ml to 44.8 +/- 13.0 microU/ml and 7.5 +/- 2.6 microU/ml to 15.2 +/- 2.5 microU/ml respectively. Insulin concentrations peaked at 75 min in the group as a whole and between 60-90 min in individual animals. Absorption was most pronounced in pigs given aprotinin (a trypsin inhibitor) with insulin. 3. Plasma portal vein glucose concentrations fell from 76.2 +/- 8.9 mg/dl to 31.1 +/- 3.2 mg/dl 150 min after encapsulated insulin administration. Corresponding systemic glucose levels were 84.5 +/- 11.0 mg/dl and 37.0 +/- 1.4 mg/dl. 4. Colonic administration of insulin in methacrylic acid coated capsules results in peak portal and systemic insulin levels 60-90 min after administration. Co-administration of aprotinin enhances the fraction of insulin absorbed.
Elias
A N
AN
Department of Medicine, University of California, Irvine 92717.
Gordon
I
I
Vaziri
N D
ND
Chune
G
G
Pandian
M R
MR
Gwinup
G
G
Wesley
R
R
D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002214:Capsules; D005260:Female; D005934:Glucagon / Q000097:blood; D006499:Hepatic Artery; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D008102:Liver Circulation; D008689:Methacrylates / Q000737:chemistry; D010180:Pancreatectomy; D011169:Portal Vein; D013552:Swine
D001786:Blood Glucose; D002096:C-Peptide; D002214:Capsules; D007328:Insulin; D008689:Methacrylates; C008384:methacrylic acid; D005934:Glucagon; D007611:Aprotinin