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Circulating Fibroblast Growth Factor-21 Is Elevated in Impaired Glucose Tolerance and Type 2 Diabetes and Correlates With Muscle and Hepatic Insulin Resistance
Open accessAbstract
OBJECTIVE: Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates hepatic glucose production and lipid metabolism in rodents. However, its role in the pathogenesis of type 2 diabetes in humans remains to be defined. The aim of this study was to quantitate circulating plasma FGF-21 levels and examine their relationship with insulin sensitivity in subjects with varying degrees of obesity and glucose tolerance. RESEARCH DESIGN AND METHODS: Forty-one subjects (8 lean with normal glucose tolerance [NGT], 9 obese with NGT, 12 with impaired fasting glucose [IFG]/impaired glucose tolerance [IGT], and 12 type 2 diabetic subjects) received an oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp (80 mU/m2 per min) combined with 3-[3H] glucose infusion. RESULTS: Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT. Plasma FGF-21 levels progressively increased from 3.9 ± 0.3 ng/ml in lean subjects with NGT to 4.9 ± 0.2 in obese subjects with NGT to 5.2 ± 0.2 in subjects with IGT and to 5.3 ± 0.2 in type 2 diabetic subjects. FGF-21 levels correlated inversely with whole-body (primarily reflects muscle) insulin sensitivity (r = −0.421, P = 0.007) and directly with the hepatic insulin resistance index (r = 0.344, P = 0.034). FGF-21 levels also correlated with measures of glycemia (fasting plasma glucose [r = 0.312, P = 0.05], 2-h plasma glucose [r = 0.414, P = 0.01], and A1C [r = 0.325, P = 0.04]). CONCLUSIONS: Plasma FGF-21 levels are increased in insulin-resistant states and correlate with hepatic and whole-body (muscle) insulin resistance. FGF-21 may play a role in pathogenesis of hepatic and whole-body insulin resistance in type 2 diabetes.
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“Circulating levels of FGF21 are significantly elevated in humans during pathophysiological states, including type 2 diabetes (16, 18), obesity (22, 30, 93), hepatosteatosis (30, 79, 146), pancreatitis (117, 137), and mitochondrial dysfunction (78).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [16]
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“FGF21 is also increased in settings of obesity”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [134]
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Self-citationFGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125
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Identification of a novel FGF, FGF-21, preferentially expressed in the liver
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Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Koliaki, C., Szendroedi, J., Kaul, K., Jelenik, T., Nowotny, P., Jankowiak, F., Herder, C., Carstensen, M., Krausch, M., Knoefel, W. T., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.04.004 · Cited by 1,032
Understanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912
The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes
Gaich, G., Chien, J. Y., Fu, H., Glass, L. C., Deeg, M. A., Holland, W. L., Kharitonenkov, A., Bumol, T., Schilske, H. K., & Moller, D. E. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.005 · Cited by 885
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Metadata
- Authors
- Chavez, A. O., Molina-Carrion, M., Abdul-Ghani, M. A., Folli, F., DeFronzo, R. A., & Tripathy, D.
- Affiliations
- From the Division of Diabetes, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Tripathy, Devjit
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2009-06-01
- Volume
- 32
- Issue
- 8
- Pages
- 1542-1546
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2713625
- OpenAlex
- W2131044927
- Cited by
- 390
- References
- 29
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 24 · 2023: 32 · 2022: 22 · 2021: 30 · 2020: 30 · 2019: 24 · 2018: 30 · 2017: 27 · 2016: 32 · 2015: 33 · 2014: 17 · 2013: 22 · 2012: 18
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- FGF21, type 2 diabetes, impaired glucose tolerance, insulin resistance, hepatic insulin resistance, skeletal muscle insulin sensitivity, obesity, impaired fasting glucose, glycemia, hyperinsulinemic-euglycemic clamp
- MeSH terms
- Adult, Blood Pressure, Diabetes Mellitus, Type 2, Fibroblast Growth Factors, Glucose Tolerance Test, Humans, Insulin Resistance, Liver, Middle Aged, Obesity, Reference Values, Glucose Clamp Technique, Body Mass Index, Glucose Intolerance, Muscle, Skeletal
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