The role of
incretins in
glucose homeostasis is well known. Yet, in recent years, the sustained
weight loss and rapid
glycemic control following
bariatric surgery has challenged our understanding of the intestinal-pancreatic interaction. This in turn led to the introduction of
metabolic surgery, an innovative medical discipline in which a surgical manipulation of the gastrointestinal tract (e. g., through a
Roux-en-Y gastric bypass, RYGB, or
Bilio-Pancreatic-Diversion, BPD) yields a sustained remission of
diabetes mellitus. The pathophysiological background of this metabolic effect is, amongst other things, based on the anti-
incretin theory. This theory postulates that in addition to the well-known
incretin effect, nutrient passage through the GI-tract could also activate negative feedback mechanisms (anti-
incretins) to balance the effects of
incretins and other postprandial
glucose-lowering mechanisms (i. e., suppression of
ghrelin,
glucagon, and hepatic
glucose production via activation of nutrient sensing). This in turn prevents postprandial hyperinsulinemic
hypoglycemia. The bypass of the duodenum, the entire jejunum and the first portion of the ileum by BPD induce normalization of peripheral
insulin sensitivity, while the bypass of a shorter intestinal tract by RYGB mainly improves the hepatic
insulin sensitivity. In addition, RYGB greatly increases insulin secretion. Therefore,
metabolic surgery highlights the important role of the small intestine in
glucose homeostasis, while until few years ago, it was only the pancreas and the liver that were thought to represent the regulatory organs for
glucose disposal.