Glucagon‐like peptide‐1 secretion by direct stimulation of L cells with luminal sugar vs non‐nutritive sweetener

Abstract

Aims/Introduction: Oral ingestion of carbohydrate triggers secretion of glucagon‐like peptide (GLP)‐1, which inhibits the postprandial rise in blood glucose levels. However, the mechanism of carbohydrate‐induced GLP‐1 secretion from enteroendocrine L cells remains unclear. In the present study, GLP‐1 secretion was examined by meal tolerance tests of healthy Japanese volunteers.Materials and Methods: Twenty‐one healthy Japanese men participated in the study. The meal tolerance test was performed with modified nutrient compositions, with or without pretreatment with the α‐glucosidase inhibitor acarbose, or with substitution of sucrose with an equivalent dose of sweeteners in the meal. Blood concentrations of glucose, insulin, GLP‐1, and apolipoprotein (Apo) B‐48 were measured.Results: GLP‐1 secretion started concomitant with the increase in blood glucose levels 10 min after meal ingestion. Insulin secretion started at 5 min, before the increase in blood glucose levels, reflecting the contribution of direct nutrient stimulation on the former parameter and neural regulation in the latter. Carbohydrate retention in the gut lumen induced by acarbose pretreatment extended postprandial GLP‐1 secretion and negated the increase in serum ApoB‐48 levels. GLP‐1 secretion was markedly decreased by a reduction in the amount of sucrose in the meal and was not restored by an equivalent dose of sweeteners used to compensate for the sweet taste.Conclusions: The results indicate that direct stimulation of L cells with sugar, but not sweetener, is required for carbohydrate‐induced GLP‐1 secretion. In addition, inhibition of digestion of dietary carbohydrate by α‐glucosidase inhibitors may prevent postprandial hyperglycemia by increasing GLP‐1 secretion and by inhibiting glucose absorption. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00163.x, 2011)

Accelerated oligosaccharide absorption and altered serum metabolites during oral glucose tolerance test in young Japanese with impaired glucose tolerance

“…In the ~50 years since the establishment of test solutions containing PHS, knowledge of gastrointestinal carbohydrate absorption and regulation of glucose homeostasis, especially that by incretins, has greatly advanced. We previously reported that inhibition of hydrolysis of disaccharides (sucrose or maltose) by α‐glucosidase inhibitors significantly increased secretion of glucagon‐like peptide‐1 (GLP‐1). In addition, the incretin effect has been reported to be attenuated in prediabetes.…”

Oligomerization of a Glucagon-like Peptide 1 Analog: Bridging Experiment and Simulations

“…GLP-1-(7-37) is a 31-amino-acid incretin hormone secreted by the endocrine L cells in the gut wall upon glucose intake (6), and the peptide is secreted in response to the nutrient content of the gastrointestinal tract and thus potentiates insulin exocytosis from pancreatic bcells in a glucose-dependent manner (6,7). Additionally, GLP-1 suppresses appetite, glucagon secretion, and gastric emptying, all of which contribute to inhibition of the postprandial rise in plasma glucose concentrations (8). GLP-1 is responsible for up to 60% of the postprandial insulin response (9).…”

The effects of sweeteners and sweetness enhancers on obesity and diabetes: a review

“…Similar in vitro results indicated that both sugars and artificial sweeteners (e.g. aspartame and sucralose) stimulate and increase the secretion of GLP-1 and GIP (Jang et al, 2007;Ma et al, 2009;Malaisse, 2014;Sakurai et al, 2012). However, the underlying mechanism of sweeteners induced gastrointestinal peptide secretion remains unclear.…”

“…Chol-ecystokinin (CCK) and peptide tyrosine-tyrosine (PYY) play a variety of roles in digestive processes, including reduction of food consumption and increasing satiety (Daly et al, 2013;. It has been demonstrated that oral ingestion of glucose and sucrose or directly infusing sugars, including D-isoforms of glucose, galactose and fructose and non-metabolizable analogues of glucose, 3-O-methyl-glucose and a-methyl-glucose, into intestinal lumen can activate with T1R2/T1R3 inducing and increasing GLP-1 and GIP secretion (Dyer et al, 2007;Sakurai et al, 2012;. Brown et al (2012) confirmed that diet soda sweetened with sucralose and acesulfame-K with glucose can increase GLP-1 secretion in healthy subjects.…”