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

Figure 1

Main types of bariatric surgery, from left to right. A: Sleeve gastrectomy; B: Roux-en-Y gastric bypass; C: One-anastomosis gastric bypass. Citation: IFSO. Sleeve Gastrectomy. [cited 20 December 2022]. Available from: https://www.ifso.com/sleeve-gastrectomy/[19]; IFSO. Roux-en-Y Gastric Bypass. [cited 20 December 2022]. Available from: https://www.ifso.com/roux-en-y-gastric-bypass/[20]; IFSO. One Anastomosis Gastric Bypass. [cited 20 December 2022]. Available from: https://www.ifso.com/alternative-intestinal-procedures/[21]. Copyright© Dr. Levent Efe, courtesy of IFSO, 2022.

Figure 2

Forms of biliopancreatic diversions, from left to right. A: Biliopancreatic diversion (BPD); B: BPD with duodenal switch. Citation: IFSO. Biliopancreatic Diversion (BPD). [cited 20 December 2022]. Available from: https://www.ifso.com/bilio-pancreatic-diversion/[25]; IFSO. Biliopancreatic Diversion with Duodenal Switch. [cited 20 December 2022]. Available from: https://www.ifso.com/bilio-pancreatic-diversion-with-duodenal-switch/[26]. Copyright© Dr. Levent Efe, courtesy of IFSO, 2022.

Figure 3

A schematic view of acini-islet-acinar- and alpha-amylase-dependent inhibitory pathway involved in the regulation of glucose metabolism before and after Biliopancreatic diversion surgery. A: Before biliopancreatic diversion surgery; B: After biliopancreatic diversion surgery. Incretin-dependent, quick stimulatory pathways (black) and acini-islet-acinar–dependent intrapancreatic inhibitory pathway and downregulating alpha-amylase dependent pathways, originating in the duodenum, of insulin secretion (orange and green respectively). AIA: Acini-islet-acinar.