Effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance |
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| Affiliation: | 1. Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai 200241, China;2. Siyuan Laboratory, Guangzhou Key Laboratory of Vacuum Coating Technologies and New Energy Materials, Guangdong Provincial Engineering Technology Research Center of Vacuum Coating Technologies and New Materials, Department of Physics, Jinan University, Guangzhou, Guangdong 510632, China;3. Ningxia Key Laboratory of Photovoltaic Materials, Ningxia University, Yinchuan, Ningxia 750021, PR China;4. International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan;5. Institute of Optoelectronic Materials and Devices, College of Optical and Electronic Technology, China Jiliang University, Hangzhou 310018, China;1. Service de chirurgie de la main, du membre supérieur et des nerfs périphériques, hôpital européen Georges-Pompidou (HEGP), Assistance publique–Hôpitaux de Paris (AP–HP), 20, rue Leblanc, 75908 Paris cedex 15, France;2. Faculté de médecine, université Paris-Descartes, Sorbonne Paris Cité, 75006 Paris, France;1. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA;2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;3. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA;4. Division of Hematologic Malignancies & Cellular Therapy, Duke University Health System, Durham, NC, USA;5. Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA;6. Department of Medicine, Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA, USA;7. Section of Hematology/Oncology, Department of Medicine, The David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL, USA;8. Cancer Center, Froedtert Hospital, Medical College of Wisconsin, Milwaukee, WI, USA;9. Stem Cell Transplantation Cellular Therapy and Acute Leukemia, Banner MD Anderson Cancer Center, Gilbert, AZ, USA;10. Department of Medicine, Division of Hematology and Blood and Marrow Transplant, University of California San Francisco, San Francisco, CA, USA;11. Internal Medicine and Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA;12. Hematology and Oncology, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA;13. T Cell Lymphoma Program, John Theurer Cancer Center at Hackensack Meridian Health, Hackensack Meridian Health School of Medicine, Hackensack, NJ, USA;14. Transplant and Cellular Immunotherapy Program, Northside Hospital Cancer Institute, Atlanta, GA, USA;15. Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA;p. Bristol Myers Squibb, Princeton, NJ, USA;q. Bristol Myers Squibb, Seattle, WA, USA;r. Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA;1. Ion Beam Development and Application Section, RIB Group, Variable Energy Cyclotron Centre, HBNI, 1/AF Bidhannagar, Kolkata 700064, India;2. Saha Institute of Nuclear Physics, HBNI, 1/AF Bidhannagar, Kolkata 700064, India |
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| Abstract: | ObjectiveTo determine the potential effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance and probe into the possible mechanisms.Research design and methodsTwenty-two subjects were treated with pioglitazone 30 mg/day for 4 months. At baseline and after treatment, each subject underwent an IVGTT. The acute insulin response (AIRg), the glucose disappearance rates (coefficients K) and the ratio of Δinsulin/Δglucose (ΔI/ΔG) were calculated according to IVGTT results. Hyperglycemic clamp study was conducted to determine the second-phase insulin response, insulin sensitivity index (ISI) and glucose infusion rate (GIR). Euglycemic–hyperinsulinemic clamp study was made to measure the glucose disposal rate (GDR). Plasma glucose, free fatty acids (FFAs), serum insulin and proinsulin levels were measured.ResultsAIRg unchanged (P = 0.25) after treatment, whereas the values of coefficients K (P < 0.01) and ΔI/ΔG increased (P < 0.05). The second-phase insulin response and GIR were both demonstrated marked increments (P < 0.01 and P < 0.01, respectively). Pioglitazone therapy also resulted in improvement of ISI value (P < 0.05). And the increment of GDR during the euglycemic–hyperinsulinemic clamp was also significant (P < 0.01). Furthermore, a decrease in fasting proinsulin level was observed (P < 0.001). And plasma glucose, FFAs and serum insulin levels all declined. The increase of ΔI1/ΔG1 was positively correlated with the improvement of GDR (r = 0.536, P = 0.089). And a positive relationship was observed between the change in the second-phase insulin response and change in K value (r = 0.682, P = 0.021).ConclusionsShort-term pioglitazone therapy improved beta-cell dysfunction, the mechanism might involve the attenuation of insulin resistance. |
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