Activation of sodium-glucose cotransporter 1 ameliorates hyperglycemia by mediating incretin secretion in mice
| Autor: | Junko Ito, Satoshi Mashiko, Toru Seo, Ryuichi Moriya, Takashi Shirakura |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Blood Glucose
Male endocrine system medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Incretin Gastric Inhibitory Polypeptide Carbohydrate metabolism Biology Mice Random Allocation Insulin resistance Sodium-Glucose Transporter 1 Glucagon-Like Peptide 1 Physiology (medical) Internal medicine medicine Animals Secretion Intestine Large RNA Messenger Glucose tolerance test medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction digestive oral and skin physiology Methylglucosides Glucose Tolerance Test medicine.disease Glucagon-like peptide-1 Mice Inbred C57BL Endocrinology Glucose Phlorhizin Gastrointestinal hormone Diabetes Mellitus Type 2 Hyperglycemia hormones hormone substitutes and hormone antagonists Hormone |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 297(6) |
| ISSN: | 1522-1555 |
| Popis: | Glucose ingestion stimulates the secretion of the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). Despite the critical role of incretins in glucose homeostasis, the mechanism of glucose-induced incretin secretion has not been established. We investigated the underlying mechanism of glucose-induced incretin secretion in vivo in mice. Injection of glucose at 1 g/kg in the upper intestine significantly increased plasma GIP and GLP-1 levels, whereas injection of glucose in the colon did not increase GIP or GLP-1 levels. This finding indicates that the glucose sensor for glucose-induced incretin secretion is in the upper intestine. Coadministration of a sodium-glucose cotransporter-1 (SGLT1) inhibitor, phloridzin, with glucose in the upper intestine blocked glucose absorption and glucose-induced incretin secretion. α-methyl-d-glucopyranoside (MDG), an SGLT1 substrate that is a nonmetabolizable sugar, significantly increased plasma GIP and GLP-1 levels, whereas phloridzin blocked these increases, indicating that concomitant transport of sodium ions and glucose (substrate) via SGLT1 itself triggers incretin secretion without the need for subsequent glucose metabolism. Interestingly, oral administration of MDG significantly increased plasma GIP, GLP-1, and insulin levels and reduced blood glucose levels during an intraperitoneal glucose tolerance test. Furthermore, chronic MDG treatment in drinking water (3%) for 13 days reduced blood glucose levels after a 2-h fast and in an oral glucose tolerance test in diabetic db/db mice. Our findings indicate that SGLT1 serves as the intestinal glucose sensor for glucose-induced incretin secretion and that a noncalorigenic SGLT1 substrate ameliorates hyperglycemia by stimulating incretin secretion. |
| Databáze: | OpenAIRE |
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