title: Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents.
abstract: Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1-3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase insulin secretion in response to glucose during a hyperglycemic clamp after 1-wk of treatment in type 2 diabetic patients. However, whether the β-cell stimulatory effect of imeglimin is solely or partially responsible for its effects on glycemia remains to be fully confirmed. Here, we show that imeglimin directly activates β-cell insulin secretion in awake rodents without affecting hepatic insulin sensitivity, body composition, or energy expenditure. These data identify a primary amplification rather than trigger the β-cell mechanism that explains the acute, antidiabetic activity of imeglimin.
authors.affiliation: Departments of Internal Medicine and.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Perry
authors.affiliation: Departments of Internal Medicine and.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Cardone
authors.affiliation: Departments of Internal Medicine and Cellular and Molecular Physiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut;
authors.forename: Max C
authors.initials: MC
authors.lastname: Petersen
authors.affiliation: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut;
authors.forename: Dongyan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Poxel SA, Paris, France; and.
authors.forename: Pascale
authors.initials: P
authors.lastname: Fouqueray
authors.affiliation: Poxel SA, Paris, France; and.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hallakou-Bozec
authors.affiliation: Poxel SA, Paris, France; and.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bolze
authors.affiliation: Departments of Internal Medicine and Cellular and Molecular Physiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut; Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark.
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.affiliation: Departments of Internal Medicine and Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark.
authors.forename: Kitt Falk
authors.initials: KF
authors.lastname: Petersen
authors.affiliation: Departments of Internal Medicine and Cellular and Molecular Physiology and richard.kibbey@yale.edu.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Kibbey
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat; D005215:Fasting; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019518:Postprandial Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D014227:Triazines; D005947:Glucose; C575881:imeglimin
keywords: glucose-stimulated insulin secretion; imeglimin; β-cell