Decreased insulin secretion and glucose clearance in exocrine pancreas‐insufficient pigs

Abstract

New Findings r What is the central question of this study? Does the exocrine pancreas have an impact on endocrine pancreatic function and peripheral nutrient utilization? r 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

Enteral Pancreatic-like Enzymes of Microbial Origin affect Insulin Release during an Intravenous Glucose Tolerance Test

“…AKG addition to enzyme supplementation had no effect on the parameters investigated. which has also been confirmed by our lab, using a pig model [3]. In order to understand the purpose of the current study, as well as our hypothesis, one should consider that pancreatic enzymes are not only responsible for digestion, but also exhibit a positive influence on the luminal intestinal mucosa [27,28].…”

“…However, other studies have observed no effect [10][11][12]. By using young pigs with induced exocrine pancreatic insufficiency, we found that the presence of pancreatic enzymes in the gut lumen resulted in improved direct utilization of blood glucose and improved growth performance, without reinforcing insulin release [3]. Thus, we were interested to investigate whether exogenous digestive enzymes could alter glucose tolerance or insulin response in healthy pigs, especially during the growth period, using microbial enzymes, which mimic endogenous digestive pancreatic enzymes and are widely available.…”

“…It was shown, that different proteases vary in cleavage sites on the proteaseactivated receptors (PAR) [30]. In addition, in experiments using EPI pigs, no increases in insulin response were detected following oral administration of a commercial mixture of pancreatic digestive enzymes [3]. The ability of proteinase to attenuate insulin sensitivity is perhaps related to its ability to potentiate inflammation [31].…”

“…This could be achieved by using appropriate functional dietary supplements, which in turn could trigger alternative mechanisms of glucose assimilation. Results from previous studies in our lab have suggested that both pancreatic enzymes and AKG are involved in the regulation of blood glucose [2,3].…”

“…Blood glucose regulation is believed to be accomplished mostly by the endocrine pancreas, liver and kidneys, as well as various gastrointestinal hormones which influence insulin secretion [5,6]. However, glucose intolerance, together with a delayed insulin release has been observed during exocrine pancreatic insufficiency in both humans and pigs [3,7]. Such changes are recognized as a pancreatogenic type of diabetes (type 3c) and are suggested to occur together with exocrine pancreatic insufficiency or pancreas injury [8].…”