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

In English

Författare

Summary, in English

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.

Publiceringsår

2016

Språk

Engelska

Sidor

100-112

Publikation/Tidskrift/Serie

Experimental Physiology

Volym

101

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Wiley-Blackwell

Ämne

  • Endocrinology and Diabetes
  • Zoology

Status

Published

Forskningsgrupp

  • Appetite Regulation
  • Neuroendocrine Cell Biology

ISBN/ISSN/Övrigt

  • ISSN: 1469-445X