Influence of rosiglitazone treatment on beta-cell function in type 2 diabetes: evidence of an increased ability of glucose to entrain high-frequency insulin pulsatility.
Thiazolidinediones have well-established insulin-sensitizing effects. Their impact on insulin secretion is less clarified. Consequently, we sought to determine potential effects of a thiazolidinedione (rosiglitazone) on the beta-cell function. Twenty type 2 diabetic individuals were randomized to receive rosiglitazone (rosi) 4 mg twice daily or placebo (pla) for 13 wk. Before treatment and at the end of the treatment period, the patients underwent an iv glucose tolerance test (0.3 g/kg), a hyperglycemic (15 mmol/liter) clamp with arginine (5 g) stimulation, assessment of baseline high-frequency insulin pulsatility, and glucose-entrained insulin pulsatility (6 mg/kg.min every 10 min), and a hyperinsulinemic euglycemic clamp. Fasting plasma glucose was reduced (pla, 8.2 +/- 2.1 vs. 8.8 +/- 2.6 mmol/liter; rosi, 8.6 +/- 7.1 vs. 7.1 +/- 1.2 mmol/liter; P < 0.01), and insulin sensitivity was increased by rosiglitazone treatment (M value: pla, 5.3 +/- 1.8 vs. 5.4 +/- 1.6 mg/kg.min; rosi, 5.9 +/- 2.2 vs. 7.4 +/- 1.3 mg/kg.min; P = 0.05). First-phase insulin secretion and insulin secretory capacity were unaffected. Glucose-entrained insulin secretion was increased as assessed by spectral power analysis (P = 0.05). In conclusion, rosiglitazone treatment for 3 months in type 2 diabetic patients exerts no action on insulin secretion per se. Improved glucose-entrained high-frequency insulin pulsatility suggests an increased ability of the beta-cell to sense and respond to glucose changes within the physiological range.
Juhl
Claus B
CB
Medical Department M (Endocrinology and Diabetes), Arhus University Hospital, 8000 Arhus, Denmark. cbj@dadlnet.dk
Hollingdal
Malene
M
Pørksen
Niels
N
Prange
Age
A
Lönnqvist
Frederik
F
Schmitz
Ole
O
D001120:Arginine; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D004311:Double-Blind Method; D019277:Entropy; D005260:Female; D005947:Glucose / Q000502:physiology*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D013268:Stimulation, Chemical; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D001120:Arginine; D005947:Glucose