Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes

TY - JOUR

T1 - Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes

AU - Asmar, Meena

AU - Højberg, Patricia V

AU - Deacon, Carolyn F

AU - Hare, Kristine

AU - Holst, Jens Juul

AU - Madsbad, Sten

N1 - Copyright 2010 Elsevier B.V. All rights reserved.

PY - 2010/2/25

Y1 - 2010/2/25

N2 - This study investigated the effects of strict glycaemic control on β-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA1c: 8.0 ± 0.4%) and after four weeks of near-normalization of blood glucose (BG) using insulin (mean diurnal BG: 6.4 ± 0.3 mmol/l; HbA1c: 6.6 ± 0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (P < 0.001). The AUC amylin/C-peptide ratio was similar on both days, while AUC proinsulin/C-peptide ratio was higher with GLP-1 (P = 0.02). In the patients, amylin, C-peptide and proinsulin AUCs were unaltered by near-normoglycaemia per se. Proinsulin responses to GLP-1 were unchanged, but amylin and C-peptide AUCs increased (P < 0.05) after insulin treatment, and AUC amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P = 0.04) with GLP-1, but still higher than with saline (P = 0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks of near-normoglycaemia, whereas GLP-1 increased amylin and C-peptide secretion and amylin/C-peptide ratio. Near-normoglycaemia reduced proinsulin/C-peptide ratio during stimulation with GLP-1, suggesting that strict glycaemic control might ameliorate some of the disturbances in β-cell function characterizing T2DM.

AB - This study investigated the effects of strict glycaemic control on β-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA1c: 8.0 ± 0.4%) and after four weeks of near-normalization of blood glucose (BG) using insulin (mean diurnal BG: 6.4 ± 0.3 mmol/l; HbA1c: 6.6 ± 0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (P < 0.001). The AUC amylin/C-peptide ratio was similar on both days, while AUC proinsulin/C-peptide ratio was higher with GLP-1 (P = 0.02). In the patients, amylin, C-peptide and proinsulin AUCs were unaltered by near-normoglycaemia per se. Proinsulin responses to GLP-1 were unchanged, but amylin and C-peptide AUCs increased (P < 0.05) after insulin treatment, and AUC amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P = 0.04) with GLP-1, but still higher than with saline (P = 0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks of near-normoglycaemia, whereas GLP-1 increased amylin and C-peptide secretion and amylin/C-peptide ratio. Near-normoglycaemia reduced proinsulin/C-peptide ratio during stimulation with GLP-1, suggesting that strict glycaemic control might ameliorate some of the disturbances in β-cell function characterizing T2DM.

KW - Amyloid

KW - Area Under Curve

KW - Blood Glucose

KW - C-Peptide

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Glucagon-Like Peptide 1

KW - Glucose

KW - Humans

KW - Incretins

KW - Insulin

KW - Insulin-Secreting Cells

KW - Islet Amyloid Polypeptide

KW - Male

KW - Middle Aged

KW - Proinsulin

KW - Time Factors

U2 - 10.1016/j.regpep.2009.12.004

DO - 10.1016/j.regpep.2009.12.004

M3 - Journal article

C2 - 20005261

SN - 0167-0115

VL - 160

SP - 175

EP - 180

JO - Regulatory Peptides

JF - Regulatory Peptides

IS - 1-3

ER -