Hypothesis that alpha-amylase evokes regulatory mechanisms originating in the pancreas, gut and circulation, which govern glucose/insulin homeostasis

Abstract

The anti-incretin theory involving the abolishment of diabetes type (DT) II by some of methods used in bariatric surgery, first appeared during the early years of the XXI century and considers the existence of anti-incretin substances. However, to date no exogenous or endogenous anti-incretins have been found. Our concept of the acini-islet-acinar axis assumes that insulin intra-pancreatically stimulates alpha-amylase synthesis (“halo phenomenon”) and in turn, alpha-amylase reciprocally inhibits insulin production, thus making alpha-amylase a candidate for being an anti-incretin. Additionally, gut as well as plasma alpha-amylase, of pancreatic and other origins, inhibits the appearance of dietary glucose in the blood, lowering the glucose peak after iv or oral glucose loading. This effect of alpha-amylase can be interpreted as an insulin down regulatory mechanism, possibly limiting the depletion of pancreatic beta cells and preventing their failure. Clinical observations agree with the above statements, where patients with high blood alpha-amylase concentrations are seldom obese and seldom develop DT2. Obese-DT2, as well as DT1 patients, usually develop exo-crine pancreatic insufficiency (EPI) and vice versa. Ultimately, DT2 patients develop DT1, when the pancreatic beta cells are exhausted and insulin production ceases. Studies on biliopancreatic diversion (BPD) and on BPD with duodenal switch, a type of bariatric surgery, as well as studies on EPI pigs, allow us to observe and investigate the above-mentioned phenomena of intra-pancreatic interactions.

Keywords: Pancreas; Alpha-amylase; Acini-islet-acinar axis; Hyperglycaemia; Bariatrics; Insulin; Incretins; Glucose-dependent insulinotropic polypeptide; Glucagon-like peptide-1; Exocrine pancreatic insufficiency; Pancreatic enzyme therapy; Diabetes

Core Tip: The concept of the acini-islet-acinar axis postulates that insulin stimulates amylase synthesis and amylase in turn inhibits insulin production. This regulation is of particular significance with regards to postoperative glucose regulation after bariatric bypass surgery. The interaction of salivary amylase at the alimentary limb and pancreatic amylase, exclusively at the common channel, results in an immediate metabolic effect that leads to a significant reduction in incretin-induced hyperinsulinaemia and a marked improvement in glucose action on insulin production. As a result, both pancreatic beta cells and acinar cells are effectively protected against depletion.