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Am J Physiol Endocrinol Metab. 2016 Aug 1;311(2):E461-70. doi: 10.1152/ajpendo.00009.2016. Epub 2016 Jul 12.

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

Author information

1
Departments of Internal Medicine and.
2
Departments of Internal Medicine and Cellular and Molecular Physiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut;
3
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut;
4
Poxel SA, Paris, France; and.
5
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.
6
Departments of Internal Medicine and Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark.
7
Departments of Internal Medicine and Cellular and Molecular Physiology and richard.kibbey@yale.edu.

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.

KEYWORDS:

glucose-stimulated insulin secretion; imeglimin; β-cell

PMID:
27406738
PMCID:
PMC5005968
DOI:
10.1152/ajpendo.00009.2016
[Indexed for MEDLINE]
Free PMC Article

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