title: Decreased insulin secretion and glucose clearance in exocrine pancreas-insufficient pigs.
abstract: The effect of exocrine pancreatic function on the glucose-mediated insulin response and glucose utilization were studied in an exocrine pancreas-insufficient (EPI) pig model. Five 10-week-old EPI pigs after pancreatic duct ligation and 6 age-matched, non-operated control pigs were used in the study. Blood glucose, plasma insulin and C-peptide concentrations were monitored during meal (MGTT), oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. Upon post-mortem examination, the pancreatic remnants of the EPI pigs showed acinar fibrotic atrophy but normal islets and β-cell morphology. The EPI pigs displayed increased fasting glucose concentrations compared with control animals (6.4 ± 0.4 versus 4.8 ± 0.1 mmol l(-1) , P < 0.0001) but unchanged insulin concentrations (2.4 ± 0.6 versus 2.1 ± 0.2 pmol l(-1) ). During the OGTT and IVGTT, the EPI pigs showed slower, impaired glucose utilization, with the disruption of a well-timed insulin response. Plasma C-peptide concentrations confirmed the delayed insulin response during the IVGTT in EPI pigs. Oral pancreatic enzyme supplementation (PES) of EPI pigs improved glucose clearance during IVGTT [AUC(glucose) 1295 ± 70 mmol l(-1) × (120 min) in EPI versus 1044 ± 32 mmol l(-1) × (120 min) in EPI + PES, P < 0.0001] without reinforcing the release of insulin [AUC(C-peptide) 14.4 ± 3.8 nmol l(-1) × (120 min) in EPI versus 6.4 ± 1.3 nmol l(-1) × (120 min) in EPI + PES, P < 0.002]. The results suggest the existence of an acino-insular axis regulatory communication. The presence of pancreatic enzymes in the gut facilitates glucose utilization in an insulin-independent manner, indicating the existence of a gut-derived pancreatic enzyme-dependent mechanism involved in peripheral glucose utilization.
authors.affiliation: Department of Biology, Lund University, Lund, Sweden.
authors.forename: Liudmyla
authors.initials: L
authors.lastname: Lozinska
authors.affiliation: Department of Biology, Lund University, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Weström
authors.affiliation: Department of Biology, Lund University, Lund, Sweden.
authors.forename: Olena
authors.initials: O
authors.lastname: Prykhodko
authors.affiliation: Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lindqvist
authors.affiliation: Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
authors.affiliation: Department of Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.affiliation: Department of Biology, Lund University, Lund, Sweden.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szwiec
authors.affiliation: Department of Biology, Lund University, Lund, Sweden.|Department of Medical Biology, Institute of Rural Health, Lublin, Poland.
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Pierzynowski
mesh_terms: D000818:Animals; D001284:Atrophy; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000378:metabolism; D004435:Eating; D005355:Fibrosis; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000473:pathology; D007515:Islets of Langerhans / Q000473:pathology; D008026:Ligation; D046790:Pancreas, Exocrine; D010183:Pancreatic Ducts / Q000601:surgery; D034421:Sus scrofa; D013552:Swine; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin