Influence of Rosiglitazone Treatment on β-Cell Function in Type 2 Diabetes: Evidence of an Increased Ability of Glucose to Entrain High-Frequency Insulin Pulsatility

• Published in: The journal of clinical endocrinology and metabolism 2003-08, Vol.88 (8), p.3794-3800
• Main Authors: Juhl, Claus B., Hollingdal, Malene, Pørksen, Niels, Prange, Åge, Lönnqvist, Frederik, Schmitz, Ole
• Format: Article
• Language: English
• Subjects: Arginine; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Double-Blind Method; Entropy; Female; Glucose - physiology; Glucose Clamp Technique; Humans; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin - metabolism; Insulin - physiology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Male; Medicin och hälsovetenskap; Middle Aged; Stimulation, Chemical; Thiazoles - therapeutic use; Thiazolidinediones
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-021181

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 β-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 β-cell to sense and respond to glucose changes within the physiological range.