Experiments suggesting extra-digestive effects of enteral pancreatic amylase and its peptides on glucose homeostasis in a pig model

Abstract

The studies presented were designed to highlight the impact of pancreatic enzymes on glycemic control and insulin response. Blood glucose and plasma insulin levels were monitored after intravenous, oral or direct gut glucose tolerance tests (GTT) in 6 pigs with an intact gastrointestinal tract and in 12 pigs following duodenal-jejunal bypass (DJB) surgery. In the intact pigs, pancreatic enzymes (Creon®) given orally 1 h prior to the GTT, lowered the blood glucose levels during the oral and meal GTT and reduced the plasma insulin response during the intravenous and meal GTT. In DJB pigs, blood glucose and plasma insulin levels were higher following glucose loading into the by-passed biliopancreatic limb as compared to that following glucose loading orally or into the common intestinal limb. Infusion of amylase or amylase peptides together with glucose into the biliopancreatic limb lowered blood glucose levels in DJB pigs. These preliminary data suggest new, extra-digestive, actions of enteral pancreatic enzymes – probably amylase or its peptides – on glucose homeostasis, with an reduction in net glucose absorption into the blood and in insulin response. This ability of digestive enzymes (amylase) to reduce post-prandial hyperglycaemia in an insulin-independent manner could aid in preventing the development of obesity and diabetes.

Exercise Affects Blood Glucose Levels and Tissue Chromium Distribution in High-Fat Diet-Fed C57BL6 Mice

“…Thus, exercise may have caused the mobilization of chromium levels in tissues and organs, which prevented mice fed an HFD from developing symptoms of hyperglycemia in addition to acini-islet-acinar (AIA) axis communication, which is crucial for developing obesity and type 2 diabetes [33]. AIA feedback links the endocrine and exocrine parts of the pancreas and emphasizes the essential role a single organ plays in regulating glucose homeostasis by using amylase, most likely in the gut epithelium, and by using insulin and glucagon in peripheral blood [33,34]. Altogether, studies on chromium links to the AIA axis are necessary for assessing possible effects on obesity and diabetes treatment.…”

Glucose homeostasis dependency on acini–islet–acinar (AIA) axis communication: a new possible pathophysiological hypothesis regarding diabetes mellitus

“…For example, we have proven that enteral administration of acinar enzymes help to control insulin production and/or release in response to a glucose challenge 40 . Recently, we have shown that pancreatic enzymes have extra-digestive properties at the gut level, which are involved in the regulation of glucose absorption and metabolism; oral administration of a pancreatic enzyme supplement 1h prior to an oral or meal glucose tolerance test (GTT) lowered blood glucose, whereas after an iv GTT glucose elimination was slowed together with reduced insulin response to the challenge 48 . The response may be owing to amylase as intestinal infusion of pancreatic amylase or amylase-derived peptides similarly lowered blood glucose to intestinal glucose challenge 48 .…”

“…Recently, we have shown that pancreatic enzymes have extra-digestive properties at the gut level, which are involved in the regulation of glucose absorption and metabolism; oral administration of a pancreatic enzyme supplement 1h prior to an oral or meal glucose tolerance test (GTT) lowered blood glucose, whereas after an iv GTT glucose elimination was slowed together with reduced insulin response to the challenge 48 . The response may be owing to amylase as intestinal infusion of pancreatic amylase or amylase-derived peptides similarly lowered blood glucose to intestinal glucose challenge 48 . Interestingly, enterally administered microbial amylase was also found to lower the insulin response required for glucose utilization during an iv glucose tolerance test 47 , 48 .…”

“…The response may be owing to amylase as intestinal infusion of pancreatic amylase or amylase-derived peptides similarly lowered blood glucose to intestinal glucose challenge 48 . Interestingly, enterally administered microbial amylase was also found to lower the insulin response required for glucose utilization during an iv glucose tolerance test 47 , 48 . Taking into account other studies where reduced blood amylase concentrations were associated with glucose intolerance, we speculate that the mechanism behind these findings is based on the specific signal transduction of enteral or parenteral amylase or amylase-derived components/peptides, which interact with the glycoconjugates—possibly receptors on the apical or basolateral surface of the enterocyte 48 .…”

“…It is well known that the growth and maturation of the intestinal mucosa is moderated/accelerated by exogenous pancreatic or bacterial proteinases 43 , whereas elevated proteinase activity in the adult gut can increase para-cellular gut permeability, thus deteriorating intestinal barrier function 44 – 46 . Recent findings suggest that glucose/insulin homeostasis can be partially regulated by extra-digestive properties of enterally applied pancreatic amylase and protease 47 , 48 . Further studies show that intravenous (iv) infusion of amylase reduces the production of insulin and C-peptide, without influencing glucose tolerance in response to an iv glucose load 30 , showing there may be an extended acini–islet feedback mechanism.…”