Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release

Abstract

We investigated the effect of acarbose, an alpha-glucosidase and pancreatic alpha-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 (r = 0.68, P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.

Effects of miglitol, vildagliptin, or their combination on serum insulin and peptide YY levels and plasma glucose, cholecystokinin, ghrelin, and obestatin levels

“…In this study, we demonstrated that combination therapy decreased the increment in the total PYY level induced by the administration of miglitol. PYY 1-36 is considered to be increased by the administration of miglitol, based on its pharmacological effect, and also to be increased by the administration of vildagliptin, as previously reported [28]. Therefore, the combination therapy increased the PYY 1-36 level and decreased the PYY 3-36 level, leaving the total PYY level unaffected when compared with that of the control group.…”

“…The administration of acarbose reportedly increased the postprandial CCK level in healthy men, although the mechanism responsible for this increase was unclear [28]. Unlike acarbose, miglitol is partially absorbed from the proximal portion of the small intestine [29], and this leads to a decrease in absorbed carbohydrates from the proximal portions of the small intestine.…”

“…The plasma glucose and serum insulin levels were measured by Hokenkagaku Institute Inc. (Yokohama, Japan). The serum total PYY (PYY 1-36 and PYY ) and plasma obestatin levels were measured using an EIA kit (Yanaihara Institute Inc., Shizuoka, Japan), and the plasma CCK (CCK [26][27][28][29][30][31][32][33] ) levels were also measured using an EIA kit (Phoenix Pharmaceutical, Inc., USA). Active ghrelin was measured using an ELISA (Sceti, Tokyo, Japan).…”

Comparison of Efficacies of a Dipeptidyl Peptidase IV Inhibitor and α-Glucosidase Inhibitors in Oral Carbohydrate and Meal Tolerance Tests and the Effects of Their Combination in Mice

“…Acarbose (28,29), voglibose (30), and miglitol (31) have been shown to enhance the GLP-1 response in healthy volunteers and type 2 diabetic patients. It is possible that the difference of GLP-1 levels between our study and these papers is due to the difference of the determination methods of GLP-1.…”

Glucose-Sensing in Glucagon-Like Peptide-1-Secreting Cells

“…Infusion of glucose in rat, pig, and dog (13)(14)(15) or carbohydrate in human (41) directly into the ileal lumen triggers GLP-1 secretion. Retarding sugar absorption in humans using the ␣-glucosidase inhibitor acarbose results in earlier and larger increments in plasma GLP-1 levels, which has been attributed to the greater supply of sugar reaching distal populations of L-cells (42,43). The reactive hypoglycemia observed in dumping syndrome, which is associated with the arrival of high concentrations of sugar in the distal small intestine and colon, has also been attributed to increased GLP-1 release (44,45).…”