Anti‐incretin effect: The other face of Janus in human glucose homeostasis

Abstract

The provocative idea that type 2 diabetes (T2D) may be a surgically treated disorder is based on accumulating evidence suggesting impressive remission rates of obesity and diabetes following bariatric surgery interventions. According to the "anti-incretin" theory, ingestion of food in the gastrointestinal (GI) tract, apart from activating the welldescribed incretin effect, also results in the parallel stimulation of a series of negative feedback mechanisms (anti-incretin effect). The primary goal of these regulations is to counteract the effects of incretins and other postprandial glucose-lowering adaptive mechanisms. Disruption of the equilibrium between incretins and anti-incretins could be an additional pathway leading to the development of insulin resistance and hyperglycemia. This theory provides an alternative theoretical framework to explain the mechanisms behind the optimal effects of metabolic surgery on T2D and underlines the importance of the GI tract in the homeostatic regulation of energy balance in humans. The anti-incretin concept is currently based on a limited amount of evidence and certainly requires further validation by additional studies. The aim of the present review is to discuss and critically evaluate recent evidence on the anti-incretin theory, providing an insight into current state and future perspectives.

Seasonal Regulation of Metabolism: The Effect of Wintertime Fasting and Autumnal Fattening on Key Central Regulators of Metabolism and the Metabolic Profile of the Raccoon Dog (Nyctereutes Procyonoides)

“…Also, the interplay of the gut-brain axis plays an important role in regulating satiety, food intake and metabolism. The hypothalamus receives signals of digesting and processing food from the gastrointestinal tract (e.g., peptide YY, ghrelin, cholecystokinin, glucose-dependent insulinotropic peptide) [ 27 , 28 , 29 ], which are likely modulated during the seasonal hyperphagia and fasting in the raccoon dog. In addition, signals from processed food directly affect food intake and the fluctuations in energy levels can be captured at the metabolic level.…”