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

Meena Asmar, Patricia V Højberg, Carolyn F Deacon, Kristine Hare, Jens Juul Holst, Sten Madsbad

Research output: Contribution to journalJournal articleResearchpeer-review

5 Citations (Scopus)

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.
Original languageEnglish
JournalRegulatory Peptides
Volume160
Issue number1-3
Pages (from-to)175-80
Number of pages6
ISSN0167-0115
DOIs
Publication statusPublished - 2010

Keywords

  • Amyloid
  • Area Under Curve
  • Blood Glucose
  • C-Peptide
  • Diabetes Mellitus, Type 2
  • Female
  • Glucagon-Like Peptide 1
  • Glucose
  • Humans
  • Incretins
  • Insulin
  • Insulin-Secreting Cells
  • Islet Amyloid Polypeptide
  • Male
  • Middle Aged
  • Proinsulin
  • Time Factors

Cite this