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


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).
Department of Clinical Cell Biology and Medicine ; Department of Diabetes, Metabolism and Endocrinology.
Kenichi
K
Sakurai
Department of Medical Physiology.
Eun Young
EY
Lee
Department of Medical Physiology.
Asuka
A
Morita
Department of Biochemistry and Molecular Pharmacology.
Sadao
S
Kimura
Department of Diabetes, Metabolism and Endocrinology ; Department of Medical Physiology.
Harukiyo
H
Kawamura
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba.
Atsushi
A
Kasamatsu
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba.
Masashi
M
Shiiba
Department of Medicine, Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, Osaka, Japan.
Daisuke
D
Yabe
Department of Clinical Cell Biology and Medicine ; Department of Diabetes, Metabolism and Endocrinology.
Koutaro
K
Yokote
Department of Diabetes, Metabolism and Endocrinology ; Department of Medical Physiology.
Takashi
T
Miki
Acarbose; Apolipoprotein B‐48; Glucagon‐like peptide‐1