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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	American Journal of Physiology: Endocrinology and Metabolism
Vol/bind	311
Udgave nummer	2
Sider (fra-til)	E461-70
ISSN	0193-1849
DOI	https://doi.org/10.1152/ajpendo.00009.2016
Status	Udgivet - 1 aug. 2016

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Citationsformater

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, bind 311, nr. 2, s. 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 - Perry, Rachel J

AU - Cardone, Rebecca L

AU - Petersen, Max C

AU - Zhang, Dongyan

AU - Fouqueray, Pascale

AU - Hallakou-Bozec, Sophie

AU - Bolze, Sébastien

AU - Shulman, Gerald I

AU - Petersen, Kitt Falk

AU - Kibbey, Richard G

PY - 2016/8/1

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N2 - 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.

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 - Blood Glucose

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

KW - Rats

KW - Rats, Sprague-Dawley

KW - Triazines

KW - Journal Article

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ER -

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

Abstract

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