Exp Physiol. 2016 Jan 1;101(1):100-12. doi: 10.1113/EP085431.

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

Lozinska L1, Weström B1, Prykhodko O1, Lindqvist A2, Wierup N2, Ahrén B3, Szwiec K1, Pierzynowski SG1,4.
  • 1Department of Biology, Lund University, Lund, Sweden.
  • 2Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
  • 3Department of Clinical Sciences, Lund University, Lund, Sweden.
  • 4Department of Medical Biology, Institute of Rural Health, Lublin, Poland.

 

Abstract

NEW FINDINGS: 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.

PMID: 26663041

 

Supplements:

How to think about insulin resistance; glucose intolerance dependency on pancreatobiliary secretion

by Stefan Pierzynowski, Ludmila Lozinska, Jaroslaw Wolinski, Nadia Mosiichuk, Hlib Repich, Björn Weström and Kateryna Goncharova

Innovation Centre Edoradca, Tczew Poland.

Dept Biol, Lund Univ, Sweden.

 

Bariatric surgery often results in improved glucose tolerance prior to other changes.

Our recent not published data show that the presence of pancreatic amylase in the gut facilitates blood glucose elimination in an insulin-independent manner, indicating the existence of a gut-derived pancreatic enzyme dependent mechanism involved in peripheral glucose utilization.

Study on pig model aimed to highlight absorption of glucose loaded to different gut channels e.g., pancreatobiliary, alimentary and common formed during bariatric surgery with parallel monitoring of insulin realise.

Here we have demonstrated that glucose absorption from the gut is strongly dependent from pancreatobiliary secretion or from place of it primary loading.

Glucose absorption was significantly lower after loading to alimentary and common channels as compared to it absorption from pancreatobiliary channel. Insulin realising was also significantly lower after glucose loading to alimentary and common channels.   Moreover, permeability for metyl-glucose and other markers measured in vitro was significantly lower from alimentary and common channels as compared to that from the pancreatobiliary channel. Thus, results suggest that lack of pancreatobiliary secretion (most likely active pancreatic enzymes) in the gut is involved in the improved glucose tolerance observed following bariatric surgery. It is not excluded – but less probable – that place of glucose loading and disconnected surgically gut continuity can also affect rate of it absorption.

Our results indicate that gut (enterocytes) can actively participate in regulatation of the ratio between glucose absorbed and utilized for their own metabolism fate e.g., quicker turnover, thus actively limiting availability of glucose for central metabolism.

Proper understanding of regulations involved in observed phenomenon can become a milestone in combat with obesity. Glucose that will not be absorbed will not stimulate insulin realising and never be converted to fat. Finally, not absorbed glucose will never provokes development of diabetes type 2 – insulin resistance!

 

 

 

 

Multiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier SchönmannMultiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier Schönmann