Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents

• Published in: American journal of physiology: endocrinology and metabolism Vol. 311; no. 2; pp. E461 - E470
• Main Authors: Perry, Rachel J., Cardone, Rebecca L., Petersen, Max C., Zhang, Dongyan, Fouqueray, Pascale, Hallakou-Bozec, Sophie, Bolze, Sébastien, Shulman, Gerald I., Petersen, Kitt Falk, Kibbey, Richard G.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2016
• Series: Islet Biology
• Subjects: Animals; Blood Glucose - drug effects; Blood Glucose - metabolism; Call for Papers; Diet, High-Fat; Fasting; Glucose - metabolism; Glucose Clamp Technique; Hypoglycemic Agents - pharmacology; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Liver - drug effects; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Postprandial Period; Rats; Rats, Sprague-Dawley; Triazines - pharmacology; β-cell; imeglimin; glucose-stimulated insulin secretion
• ISSN: 0193-1849; 1522-1555; 1522-1555
• DOI: 10.1152/ajpendo.00009.2016

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 A 1c (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.