Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents
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 i...
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| Published in | American journal of physiology: endocrinology and metabolism Vol. 311; no. 2; pp. E461 - E470 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Physiological Society
01.08.2016
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| Series | Islet Biology |
| Subjects | |
| Online Access | Get full text |
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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 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. |
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| AbstractList | 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.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. 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. 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. 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. |
| Author | Shulman, Gerald I. Petersen, Max C. Petersen, Kitt Falk Hallakou-Bozec, Sophie Perry, Rachel J. Bolze, Sébastien Cardone, Rebecca L. Fouqueray, Pascale Kibbey, Richard G. Zhang, Dongyan |
| Author_xml | – sequence: 1 givenname: Rachel J. surname: Perry fullname: Perry, Rachel J. organization: Departments of Internal Medicine and – sequence: 2 givenname: Rebecca L. surname: Cardone fullname: Cardone, Rebecca L. organization: Departments of Internal Medicine and – sequence: 3 givenname: Max C. surname: Petersen fullname: Petersen, Max C. organization: Departments of Internal Medicine and, Cellular and Molecular Physiology and, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut – sequence: 4 givenname: Dongyan surname: Zhang fullname: Zhang, Dongyan organization: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut – sequence: 5 givenname: Pascale surname: Fouqueray fullname: Fouqueray, Pascale organization: Poxel SA, Paris, France; and – sequence: 6 givenname: Sophie surname: Hallakou-Bozec fullname: Hallakou-Bozec, Sophie organization: Poxel SA, Paris, France; and – sequence: 7 givenname: Sébastien surname: Bolze fullname: Bolze, Sébastien organization: Poxel SA, Paris, France; and – sequence: 8 givenname: Gerald I. surname: Shulman fullname: Shulman, Gerald I. organization: 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 – sequence: 9 givenname: Kitt Falk surname: Petersen fullname: Petersen, Kitt Falk organization: Departments of Internal Medicine and, Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark – sequence: 10 givenname: Richard G. surname: Kibbey fullname: Kibbey, Richard G. organization: Departments of Internal Medicine and, Cellular and Molecular Physiology and |
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| Cites_doi | 10.4172/2155-6156.1000126 10.1016/S0021-9258(19)50663-9 10.1016/j.cmet.2010.03.012 10.1074/jbc.M109.011775 10.2337/db14-1220 10.1172/JCI112981 10.2337/diabetes.49.11.1751 10.1111/dom.12452 10.2337/dc12-0453 10.1007/s00125-010-1685-0 10.2337/dc13-2349 10.1016/S0168-8227(11)70010-9 10.1111/j.1463-1326.2012.01611.x 10.2337/diabetes.48.6.1270 |
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| SubjectTerms | 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 |
| Title | Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents |
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