Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid-induced insulin resistance
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Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid-induced insulin resistance. / Eriksen, Marie; Jensen, David H; Tribler, Siri; Holst, Jens Juul; Madsbad, Sten; Krarup, Thure.
In: Diabetologia, Vol. 58, No. 5, 2015, p. 920-8.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Reduction of insulinotropic properties of GLP-1 and GIP after glucocorticoid-induced insulin resistance
AU - Eriksen, Marie
AU - Jensen, David H
AU - Tribler, Siri
AU - Holst, Jens Juul
AU - Madsbad, Sten
AU - Krarup, Thure
PY - 2015
Y1 - 2015
N2 - AIMS/HYPOTHESIS: We evaluated the insulinotropic properties of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in healthy individuals at risk of developing type 2 diabetes before and after glucocorticoid-induced insulin resistance.METHODS: Nineteen healthy, glucose tolerant, first-degree relatives of type 2 diabetic patients underwent OGTT and 7 mmol/l and 15 mmol/l glucose clamps with concomitant infusions of GLP-1, GIP or NaCl and a final infusion of arginine for determination of maximum beta cell capacity before and after treatment with dexamethasone. In addition, first-phase insulin responses were determined at 7 mmol/l and 15 mmol/l and second-phase insulin responses at 7 mmol/l.RESULTS: After dexamethasone treatment, all 19 participants had increased insulin resistance (HOMA-IR and insulin sensitivity index [M/I] values) and 2 h plasma glucose concentrations, while beta cell function indices generally increased according to the increased resistance. First-phase insulin responses induced by GLP-1 and GIP at 7 mmol/l and maximal beta cell secretory capacity did not differ before and after dexamethasone, while second-phase responses to 7 mmol/l and first-phase responses to 15 mmol/l glucose were reduced equally for both hormones.CONCLUSIONS/INTERPRETATION: Glucocorticoid-induced insulin resistance in individuals at risk of type 2 diabetes leads to a reduced insulinotropic effect of the incretin hormones. This reduction was not associated with a decrease in the maximal beta cell secretory capacity, indicating that the reduced incretin effect in the developing dysglycaemia of the present experimental model is due to a specific early reduction of the insulinotropic effects of the incretin hormones.TRIAL REGISTRATION: Clinicaltrials.gov NCT02235584.
AB - AIMS/HYPOTHESIS: We evaluated the insulinotropic properties of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in healthy individuals at risk of developing type 2 diabetes before and after glucocorticoid-induced insulin resistance.METHODS: Nineteen healthy, glucose tolerant, first-degree relatives of type 2 diabetic patients underwent OGTT and 7 mmol/l and 15 mmol/l glucose clamps with concomitant infusions of GLP-1, GIP or NaCl and a final infusion of arginine for determination of maximum beta cell capacity before and after treatment with dexamethasone. In addition, first-phase insulin responses were determined at 7 mmol/l and 15 mmol/l and second-phase insulin responses at 7 mmol/l.RESULTS: After dexamethasone treatment, all 19 participants had increased insulin resistance (HOMA-IR and insulin sensitivity index [M/I] values) and 2 h plasma glucose concentrations, while beta cell function indices generally increased according to the increased resistance. First-phase insulin responses induced by GLP-1 and GIP at 7 mmol/l and maximal beta cell secretory capacity did not differ before and after dexamethasone, while second-phase responses to 7 mmol/l and first-phase responses to 15 mmol/l glucose were reduced equally for both hormones.CONCLUSIONS/INTERPRETATION: Glucocorticoid-induced insulin resistance in individuals at risk of type 2 diabetes leads to a reduced insulinotropic effect of the incretin hormones. This reduction was not associated with a decrease in the maximal beta cell secretory capacity, indicating that the reduced incretin effect in the developing dysglycaemia of the present experimental model is due to a specific early reduction of the insulinotropic effects of the incretin hormones.TRIAL REGISTRATION: Clinicaltrials.gov NCT02235584.
U2 - 10.1007/s00125-015-3522-y
DO - 10.1007/s00125-015-3522-y
M3 - Journal article
C2 - 25748606
VL - 58
SP - 920
EP - 928
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 5
ER -
ID: 137419163