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The Effects of Rosiglitazone on Insulin Sensitivity, Lipolysis, and Hepatic and Skeletal Muscle Triglyceride Content in Patients With Type 2 Diabetes
Open accessAbstract
We examined the effect of three months of rosiglitazone treatment (4 mg b.i.d.) on whole-body insulin sensitivity and in vivo peripheral adipocyte insulin sensitivity as assessed by glycerol release in microdialysis from subcutaneous fat during a two-step (20 and 120 mU · m−2 · min−1) hyperinsulinemic-euglycemic clamp in nine type 2 diabetic subjects. In addition, the effects of rosiglitazone on liver and muscle triglyceride content were assessed by 1H-nuclear magnetic resonance spectroscopy. Rosiglitazone treatment resulted in a 68% (P < 0.002) and a 20% (P < 0.016) improvement in insulin-stimulated glucose metabolism during the low- and high- dosage−insulin clamps, respectively, which was associated with ∼40% reductions in plasma fatty acid concentration (P < 0.05) and hepatic triglyceride content (P < 0.05). These changes were associated with a 39% increase in extramyocellular lipid content (P < 0.05) and a 52% increase in the sensitivity of peripheral adipocytes to the inhibitory effects of insulin on lipolysis (P = 0.04). In conclusion, these results support the hypothesis that thiazolidinediones enhance insulin sensitivity in patients with type 2 diabetes by promoting increased insulin sensitivity in peripheral adipocytes, which results in lower plasma fatty acid concentrations and a redistribution of intracellular lipid from insulin responsive organs into peripheral adipocytes.
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“Previous studies by our group (9, 17-20) and others (7, 21, 22) have demonstrated a strong relationship between triglyceride content in liver and muscle and insulin resistance in these tissues.”
From Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy (2002) · cites this paper as [9]
In the citing paper
“Treatment for 3 months with rosiglitazone was associated with an almost 40% reduction in hepatic triglyceride content, and roughly 40% increase in extramyocellular triglyceride concentration, and improved suppression of adipocyte lipolysis.133”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [133]
In the citing paper
“Treatment for 3 months with rosiglitazone was associated with an almost 40% reduction in hepatic triglyceride content, and roughly 40% increase in extramyocellular triglyceride concentration, and improved suppression of adipocyte lipolysis.133”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [133]
In the citing paper
“Though no reductions in the concentration of intramyocellular triglyceride were noted in this study, rosiglitazone improved insulin-mediated whole-body glucose disposal, consistent with improvements in muscle insulin sensitivity.”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [133]
In the citing paper
“Treatment for 3 months with rosiglitazone was associated with an almost 40% reduction in hepatic triglyceride content, and roughly 40% increase in extramyocellular triglyceride concentration, and improved suppression of adipocyte lipolysis.133”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [133]
In the citing paper
“Thiazolidinediones, which are potent PPARγ agonists, can effectively reduce hepatic steatosis.133”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [133]
In the citing paper
“Moreover, reductions in intracellular diacylglycerol content account for the improvements in insulin sensitivity after weight loss81 and therapy with thiazolidinediones.133”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [133]
In the citing paper
“Though no reductions in the concentration of intramyocellular triglyceride were noted in this study, rosiglitazone improved insulin-mediated whole-body glucose disposal, consistent with improvements in muscle insulin sensitivity.”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [133]
In the citing paper
“The TZDs improve insulin resistance by increasing glucose disposal in muscle and decreasing hepatic glucose output.26”
From A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis (2004) · cites this paper as [26]
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Shaya, F. T., Calloway, S., Pharmd, C., Khoury, A. C. E., Tomety, J., & Pharmd, C. (2015)
The Percent Change of Body Weight in Patients with Type 2 Diabetes Using Rosiglitazone for 1 Year
Hong, S. B., Park, H. R., Kim, E. A., Lee, K. W., Nam, M., & Kim, Y. (2006) · The Journal of Korean Diabetes Association · doi:10.4093/jkda.2006.30.1.47
Novel pharmaceutical approaches to regulate glucose homeostasis
Sundbom, M. (2010) · Figshare
Metadata
- Authors
- Mayerson, A. B., Hundal, R. S., Dufour, S., Lebon, V., Befroy, D., Cline, G. W., Enocksson, S., Inzucchi, S. E., Shulman, G. I., & Petersen, K. F.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-03-01
- Volume
- 51
- Issue
- 3
- Pages
- 797-802
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2995527
- OpenAlex
- W2100514340
- Cited by
- 647
- References
- 53
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 11 · 2023: 15 · 2022: 4 · 2021: 5 · 2020: 7 · 2019: 20 · 2018: 12 · 2017: 15 · 2016: 15 · 2015: 22 · 2014: 20 · 2013: 22 · 2012: 16
- FWCI
- 24.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- Deutsches Krebsforschungszentrum
- U.S. Public Health Service
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, R01DK049230, R01 DK-49230, K23DK002734, P30DK045735)
- National Center for Research Resources (M01RR000125, M01 RR-00125)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- rosiglitazone, thiazolidinediones, type 2 diabetes, insulin sensitivity, hepatic triglyceride content, extramyocellular lipids, plasma fatty acids, hyperinsulinemic-euglycemic clamp, microdialysis, lipid redistribution
- MeSH terms
- Rosiglitazone, Adipose Tissue, Blood Glucose, Body Composition, Calorimetry, Indirect, Diabetes Mellitus, Type 2, Fatty Acids, Glycerol, Glycated Hemoglobin, Humans, Hyperinsulinism, Insulin, Kinetics, Lipids, Lipolysis, Liver, Middle Aged, Magnetic Resonance Spectroscopy, Oxidation-Reduction, Thiazoles, Triglycerides, Glucose Clamp Technique, Microdialysis, Adipocytes, Muscle, Skeletal, Thiazolidinediones
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