Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes
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Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes. / Højberg, P V; Zander, M; Vilsbøll, T; Knop, F K; Krarup, T; Vølund, A; Holst, Jens Juul; Madsbad, S.
In: Diabetologia, Vol. 51, No. 4, 01.04.2008, p. 632-640.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Near normalisation of blood glucose improves the potentiating effect of GLP-1 on glucose-induced insulin secretion in patients with type 2 diabetes
AU - Højberg, P V
AU - Zander, M
AU - Vilsbøll, T
AU - Knop, F K
AU - Krarup, T
AU - Vølund, A
AU - Holst, Jens Juul
AU - Madsbad, S
PY - 2008/4/1
Y1 - 2008/4/1
N2 - AIMS/HYPOTHESIS: The ability of glucagon-like peptide-1 (GLP-1) to enhance beta cell responsiveness to i.v. glucose is impaired in patients with type 2 diabetes mellitus compared with healthy individuals. We investigated whether 4 weeks of near normalisation of blood glucose (BG) improves the potentiation of glucose-stimulated insulin secretion by GLP-1.METHODS: Nine obese patients with type 2 diabetes and inadequate glycaemic control (HbA(1c) 8.0+/-0.4%) were investigated before and after 4 weeks of near normalisation of BG using insulin treatment (mean diurnal blood glucose 6.4+/-0.3 mmol/l, HbA(1c) 6.6+/-0.3%). Nine matched healthy participants were also studied. Beta cell function was investigated before and after insulin treatment using stepwise glucose infusions and infusion of saline or GLP-1 (1.0 pmol kg(-1) min(-1)), resulting in supraphysiological total GLP-1 concentrations of approximately 200 pmol/l. The responsiveness to glucose or glucose+GLP-1 was expressed as the slope of the linear regression line relating insulin secretion rate (ISR) and plasma glucose concentration (pmol kg(-1) min(-1) [mmol/l](-1)).RESULTS: In the diabetic participants, the slopes during glucose+saline infusion did not differ before and after insulin treatment (0.33+/-0.07 and 0.39+/-0.04, respectively; p=NS). In contrast, near normalisation of blood glucose improved beta cell sensitivity to glucose during glucose+GLP-1 infusion (1.27+/-0.2 before vs 1.73+/-0.31 after; p<0.01). In the healthy participants, the slopes during the glucose+saline and glucose+GLP-1 infusions were 1.01+/-0.14 and 4.79+/-0.53, respectively.CONCLUSIONS/INTERPRETATION: A supraphysiological dose of GLP-1 enhances beta cell responses to glucose in patients with type 2 diabetes, and 4 weeks of near normalisation of blood glucose further improves this effect.
AB - AIMS/HYPOTHESIS: The ability of glucagon-like peptide-1 (GLP-1) to enhance beta cell responsiveness to i.v. glucose is impaired in patients with type 2 diabetes mellitus compared with healthy individuals. We investigated whether 4 weeks of near normalisation of blood glucose (BG) improves the potentiation of glucose-stimulated insulin secretion by GLP-1.METHODS: Nine obese patients with type 2 diabetes and inadequate glycaemic control (HbA(1c) 8.0+/-0.4%) were investigated before and after 4 weeks of near normalisation of BG using insulin treatment (mean diurnal blood glucose 6.4+/-0.3 mmol/l, HbA(1c) 6.6+/-0.3%). Nine matched healthy participants were also studied. Beta cell function was investigated before and after insulin treatment using stepwise glucose infusions and infusion of saline or GLP-1 (1.0 pmol kg(-1) min(-1)), resulting in supraphysiological total GLP-1 concentrations of approximately 200 pmol/l. The responsiveness to glucose or glucose+GLP-1 was expressed as the slope of the linear regression line relating insulin secretion rate (ISR) and plasma glucose concentration (pmol kg(-1) min(-1) [mmol/l](-1)).RESULTS: In the diabetic participants, the slopes during glucose+saline infusion did not differ before and after insulin treatment (0.33+/-0.07 and 0.39+/-0.04, respectively; p=NS). In contrast, near normalisation of blood glucose improved beta cell sensitivity to glucose during glucose+GLP-1 infusion (1.27+/-0.2 before vs 1.73+/-0.31 after; p<0.01). In the healthy participants, the slopes during the glucose+saline and glucose+GLP-1 infusions were 1.01+/-0.14 and 4.79+/-0.53, respectively.CONCLUSIONS/INTERPRETATION: A supraphysiological dose of GLP-1 enhances beta cell responses to glucose in patients with type 2 diabetes, and 4 weeks of near normalisation of blood glucose further improves this effect.
KW - Blood Glucose
KW - Body Mass Index
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Glucagon-Like Peptide 1
KW - Glucose
KW - Humans
KW - Insulin
KW - Kinetics
KW - Male
KW - Middle Aged
KW - Peptide Fragments
KW - Reference Values
U2 - 10.1007/s00125-008-0943-x
DO - 10.1007/s00125-008-0943-x
M3 - Journal article
C2 - 18292985
VL - 51
SP - 632
EP - 640
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 4
ER -
ID: 9590536