This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Juhl, C. B. Articles by Schmitz, O. Search for Related Content PubMed PubMed Citation Articles by Juhl, C. B. Articles by Schmitz, O.

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

Medical Department M (Endocrinology and Diabetes) (C.B.J., M.H., N.P., O.S.), Århus University Hospital, 8000 Århus, Denmark; Medical Department (C.B.J., A.P.), Kolding Sygehus, 6000 Kolding, Denmark; Center for Metabolism and Endocrinology (F.L.), Huddinge University Hospital, Karolinska Institute, 17177 Stockholm, Sweden; and Institute of Clinical Pharmacology (O.S.), University of Århus, Århus, Denmark

Address all correspondence and requests for reprints to: Claus B. Juhl, M.D., Medical Department M (Endocrinology and Diabetes), Århus University Hospital, Nørrebrogade 44, 8000 Århus C, Denmark. E-mail: cbj{at}dadlnet.dk.

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

This work was supported by Glaxo-SmithKline. F.L. was employed at Glaxo-SmithKline at the time of study conductance.

Abbreviations: ApEn, Approximate entropy; AUC, area(s) under the curve; IVGTT, iv glucose tolerance test; TZD, thiazolidinedione.

This article has been cited by other articles:

				B. L. Wajchenberg {beta}-Cell Failure in Diabetes and Preservation by Clinical Treatment Endocr. Rev., April 1, 2007; 28(2): 187 - 218. [Abstract] [Full Text] [PDF]

				A. H Barnett Summarising the use of thiazolidinediones with insulin The British Journal of Diabetes & Vascular Disease, March 1, 2007; 7(2): 75 - 80. [Abstract] [PDF]

				A. Gastaldelli, E. Ferrannini, Y. Miyazaki, M. Matsuda, A. Mari, and R. A. DeFronzo Thiazolidinediones improve beta-cell function in type 2 diabetic patients Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E871 - E883. [Abstract] [Full Text] [PDF]

				M. O. Larsen, B. Rolin, J. Sturis, M. Wilken, R. D. Carr, N. Porksen, and C. F. Gotfredsen Measurements of insulin responses as predictive markers of pancreatic beta-cell mass in normal and beta-cell-reduced lean and obese Gottingen minipigs in vivo Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E670 - E677. [Abstract] [Full Text] [PDF]

				R. A. Ritzel, J. D. Veldhuis, and P. C. Butler The mass, but not the frequency, of insulin secretory bursts in isolated human islets is entrained by oscillatory glucose exposure Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E750 - E756. [Abstract] [Full Text] [PDF]

				B. Kimmel and S. E. Inzucchi Oral Agents for Type 2 Diabetes: An Update Clin. Diabetes, April 1, 2005; 23(2): 64 - 76. [Abstract] [Full Text] [PDF]

				S. A. Smith, L. E. Porter, N. Biswas, and M. I. Freed Rosiglitazone, But Not Glyburide, Reduces Circulating Proinsulin and the Proinsulin:Insulin Ratio in Type 2 Diabetes J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6048 - 6053. [Abstract] [Full Text] [PDF]

				F. Ovalle and D. S.H. Bell Effect of Rosiglitazone Versus Insulin on the Pancreatic {beta}-Cell Function of Subjects With Type 2 Diabetes Diabetes Care, November 1, 2004; 27(11): 2585 - 2589. [Abstract] [Full Text] [PDF]

				Y.-P. Zhou, K. Marlen, J. F. Palma, A. Schweitzer, L. Reilly, F. M. Gregoire, G. G. Xu, J. E. Blume, and J. D. Johnson Overexpression of Repressive cAMP Response Element Modulators in High Glucose and Fatty Acid-treated Rat Islets: A COMMON MECHANISM FOR GLUCOSE TOXICITY AND LIPOTOXICITY? J. Biol. Chem., December 19, 2003; 278(51): 51316 - 51323. [Abstract] [Full Text] [PDF]