Ghrelin, CCK, GLP-1, and PYY(3–36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB

Abstract

The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.

Comparison of the Levels of C-Reactive Protein, GLP-1 and GLP-2 Among Individuals With Diabetes, Morbid Obesity and Healthy Controls: An Exploratory Study

“…Although these hormones have been identified in the early 1970s, they really rose to prominence after the growth of bariatric surgery and the observation of the critical impact of these procedures on their release and, consequently, on the glucose homeostasis and improvement of metabolic syndrome and its clinical features (16)(17)(18)(19)(20)(21)(22)(28)(29)(30)(31)(32)(33)(34) . In this study, we observed that the GLP-1 levels did not differ among non-diabetic individuals with morbid obesity, diabetic individuals with mild obesity and healthy controls.…”

“…Both GLP-1 and GLP-2 are quickly degraded by the enzyme dipeptidil-peptidase-4 (DPP-IV), and after 60 minutes, about 69% of the original hormones remain intact. The research on gut-derived peptides has considerably increased over the last decades, especially due to the changes in their release pattern and metabolic roles played after several bariatric surgical modalities (16)(17)(18)(19)(20)(21)(22) . A witty metaphor proposed by Hein et al (23) claimed that GLP-1 and GLP-2 were "the yin and yang" of intestinal lipoprotein production, since GLP-1 significantly reduces and GLP-2 increases postprandial chylomicronemia.…”

Ghrelin is Negatively Correlated with Iron in the Serum in Human and Mice

“…Serine-3 of ghrelin is acylated with an 8-carbon fatty acid, octanoate, which is essential for its biological functions, by Ghrelin O-Acyltransferase, a polytopic membrane-bound enzyme [2, 3]. This hormone acts in the brain to regulate food intake, body weight, adiposity, and glucose metabolism [4], modulates systemic metabolism via activation of orexigenic neural circuits [5, 6] and plays other numerous functions in the central and peripheral tissues [7, 8]. …”

Gglucagon-like peptide-1 analogue liraglutide (Saxenda®): mechanism of action, efficacy for the treatment of obesity

“…Тем не менее, показатели динамики массы тела после бариатрической операции у крыс с нокау-тированным геном ГПП-1Р сопоставимы с контрольной группой животных [34]. В качестве дополнительных фак-торов, обеспечивающих благоприятное влияние опера-тивных вмешательств на энергобаланс и углеводный обмен, изучается роль других гормонов ЖКТ (пептида YY, ГПП-2, оксинтомодулина, амилина), желчных кислот, ки-шечной микрофлоры [35].…”