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

Rachel J Perry; Rebecca L Cardone; Max C Petersen; Dongyan Zhang; Pascale Fouqueray; Sophie Hallakou-Bozec; Sébastien Bolze; Gerald I Shulman; Kitt Falk Petersen; Richard G Kibbey

doi:10.1152/ajpendo.00009.2016

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

Rachel J Perry, Rebecca L Cardone, Max C Petersen, Dongyan Zhang, Pascale Fouqueray, Sophie Hallakou-Bozec, Sébastien Bolze, Gerald I Shulman, Kitt Falk Petersen, Richard G Kibbey

16 Citations (Scopus)

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.

Original language	English
Journal	American Journal of Physiology: Endocrinology and Metabolism
Volume	311
Issue number	2
Pages (from-to)	E461-70
ISSN	0193-1849
DOIs	https://doi.org/10.1152/ajpendo.00009.2016
Publication status	Published - 1 Aug 2016

Keywords

Animals
Blood Glucose
Diet, High-Fat
Fasting
Glucose
Glucose Clamp Technique
Hypoglycemic Agents
Insulin
Insulin Resistance
Insulin-Secreting Cells
Liver
Male
Mice
Mice, Inbred C57BL
Postprandial Period
Rats
Rats, Sprague-Dawley
Triazines
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1152/ajpendo.00009.2016

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Perry, R. J., Cardone, R. L., Petersen, M. C., Zhang, D., Fouqueray, P., Hallakou-Bozec, S., Bolze, S., Shulman, G. I., Petersen, K. F., & Kibbey, R. G. (2016). Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents. American Journal of Physiology: Endocrinology and Metabolism, 311(2), E461-70. https://doi.org/10.1152/ajpendo.00009.2016

Perry, RJ, Cardone, RL, Petersen, MC, Zhang, D, Fouqueray, P, Hallakou-Bozec, S, Bolze, S, Shulman, GI, Petersen, KF & Kibbey, RG 2016, 'Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents', American Journal of Physiology: Endocrinology and Metabolism, vol. 311, no. 2, pp. E461-70. https://doi.org/10.1152/ajpendo.00009.2016

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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.",

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AU - Hallakou-Bozec, Sophie

AU - Bolze, Sébastien

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AU - Kibbey, Richard G

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AB - 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.

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KW - Diet, High-Fat

KW - Fasting

KW - Glucose

KW - Glucose Clamp Technique

KW - Hypoglycemic Agents

KW - Insulin

KW - Insulin Resistance

KW - Insulin-Secreting Cells

KW - Liver

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Postprandial Period

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KW - Rats, Sprague-Dawley

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JF - American Journal of Physiology: Endocrinology and Metabolism

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

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