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

Abstract

This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 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; HbA(1)c: 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 beta-cell function characterizing T2DM.

• Authors: Meena Asmar, Patricia V Højberg, Carolyn F Deacon, Kristine Hare, Jens J Holst, Sten Madsbad
• Journal: Regulatory peptides (Regul Pept) Vol. 160 Issue 1-3 Pg. 175-80 (Feb 25 2010) ISSN: 1873-1686 [Electronic] Netherlands
• PMID: 20005261 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid
• Blood Glucose
• C-Peptide
• Incretins
• Insulin
• Islet Amyloid Polypeptide
• Glucagon-Like Peptide 1
• Proinsulin
• Glucose

Topics

• Amyloid (metabolism)
• Area Under Curve
• Blood Glucose (analysis, drug effects)
• C-Peptide (metabolism)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Female
• Glucagon-Like Peptide 1 (blood, pharmacology, therapeutic use)
• Glucose (administration & dosage)
• Humans
• Incretins (pharmacology)
• Insulin (administration & dosage, pharmacology)
• Insulin-Secreting Cells (drug effects)
• Islet Amyloid Polypeptide
• Male
• Middle Aged
• Proinsulin (metabolism)
• Time Factors