Advanced

Decreased insulin secretion and glucose clearance in exocrine pancreas-insufficient pigs.

Lozinska, Liudmyla LU ; Weström, Björn LU ; Prykhodko, Olena LU ; Lindqvist, Andreas LU ; Wierup, Nils LU ; Ahrén, Bo LU ; Szwiec, Katarzyna LU and Pierzynowski, Stefan LU (2016) In Experimental Physiology 101(1). p.100-112
Abstract
What is the central question of this study? Does the exocrine pancreas have an impact on endocrine pancreatic function and peripheral nutrient utilization? What is the main finding and its importance? In an exocrine pancreas-insufficient pig model, the insulin response to a glucose load was delayed. Oral enzyme supplementation did not improve the insulin release but facilitated blood glucose clearance. These results suggest an acino-insular axis communication affecting islet function and an impact of gut pancreatic enzymes on blood glucose utilization. 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... (More)
What is the central question of this study? Does the exocrine pancreas have an impact on endocrine pancreatic function and peripheral nutrient utilization? What is the main finding and its importance? In an exocrine pancreas-insufficient pig model, the insulin response to a glucose load was delayed. Oral enzyme supplementation did not improve the insulin release but facilitated blood glucose clearance. These results suggest an acino-insular axis communication affecting islet function and an impact of gut pancreatic enzymes on blood glucose utilization. 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 [AUCglucose 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 [AUCC-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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Physiology
volume
101
issue
1
pages
100 - 112
publisher
Wiley-Blackwell
external identifiers
  • pmid:26663041
  • wos:000368251900012
  • scopus:84949895085
ISSN
1469-445X
DOI
10.1113/EP085431
language
English
LU publication?
yes
id
639c8c4b-5841-4866-bb29-d05a9ef2078d (old id 8504934)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26663041?dopt=Abstract
date added to LUP
2016-01-05 18:56:49
date last changed
2017-10-23 13:57:51
@article{639c8c4b-5841-4866-bb29-d05a9ef2078d,
  abstract     = {What is the central question of this study? Does the exocrine pancreas have an impact on endocrine pancreatic function and peripheral nutrient utilization? What is the main finding and its importance? In an exocrine pancreas-insufficient pig model, the insulin response to a glucose load was delayed. Oral enzyme supplementation did not improve the insulin release but facilitated blood glucose clearance. These results suggest an acino-insular axis communication affecting islet function and an impact of gut pancreatic enzymes on blood glucose utilization. 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 &lt; 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 [AUCglucose 1295 ± 70 mmol l(-1) × (120 min) in EPI versus 1044 ± 32 mmol l(-1) × (120 min) in EPI + PES, P &lt; 0.0001] without reinforcing the release of insulin [AUCC-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 &lt; 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.},
  author       = {Lozinska, Liudmyla and Weström, Björn and Prykhodko, Olena and Lindqvist, Andreas and Wierup, Nils and Ahrén, Bo and Szwiec, Katarzyna and Pierzynowski, Stefan},
  issn         = {1469-445X},
  language     = {eng},
  number       = {1},
  pages        = {100--112},
  publisher    = {Wiley-Blackwell},
  series       = {Experimental Physiology},
  title        = {Decreased insulin secretion and glucose clearance in exocrine pancreas-insufficient pigs.},
  url          = {http://dx.doi.org/10.1113/EP085431},
  volume       = {101},
  year         = {2016},
}