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Cited by 518Peroxisome Proliferator-Activated ReceptorsDiabetes Treatment and ManagementMetabolism, Diabetes, and Cancer

Thiazolidinediones and the promise of insulin sensitization in type 2 diabetes

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Soccio, Raymond E., Chen, Eric R., Lazar, Mitchell A.·2014·Cell Metabolism
DOI 10.1016/j.cmet.2014.08.005PMC PMC4192012
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Abstract

Type 2 diabetes is caused by insulin resistance coupled with an inability to produce enough insulin to control blood glucose, and thiazolidinediones (TZDs) are the only current antidiabetic agents that function primarily by increasing insulin sensitivity. However, despite clear benefits in glycemic control, this class of drugs has recently fallen into disuse due to concerns over side effects and adverse events. Here we review the clinical data and attempt to balance the benefits and risks of TZD therapy. We also examine potential mechanisms of action for the beneficial and harmful effects of TZDs, mainly via agonism of the nuclear receptor PPARγ. Based on critical appraisal of both preclinical and clinical studies, we discuss the prospect of harnessing the insulin sensitizing effects of PPARγ for more effective, safe, and potentially personalized treatments of type 2 diabetes.

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  • The distinction between obesity-induced features occurring in the entire adipocyte population versus specific adipocyte subpopulations may explain the outstanding effectiveness of PPARγ agonists, such as thiazolidinediones, in improving adipose function and glucose homeostasis, surpassing the effects of other anti-inflammatory or anti-stress reagents.

    “The distinctions between obesity-induced features occurring in the entire adipocyte population versus specific adipocyte subpopulations may explain the outstanding effectiveness of PPARγ agonists, such as thiazolidinediones, in improving adipose function and glucose homeostasis (Soccio et al., 2014), surpassing the effects of other anti-inflammatory or anti-stress reagents (Kraakman et al., 2015;”

    From Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity (2025) · cites this paper as Soccio et al., 2014

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  • Recently, a few protocols have been introduced to enhance RNA quality by employing VRC or acidic buffers during nucleus isolation for snRNA-seq, particularly for kidney and pancreas samples.

    “Recently, we encountered a few protocols that have been introduced to enhance RNA quality by employing VRC or acidic buffers during nucleus isolation for snRNA-seq, particularly for kidney (Soccio et al., 2014) and pancreas (Tosti et al., 2021) samples.”

    From Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity (2025) · cites this paper as Soccio et al., 2014

    The Basic Science section discusses ChIP-seq analysis of thiazolidinedione effects, not kidney nucleus-isolation protocols. Searches for VRC, acidic buffers, RNA quality, and kidney snRNA-seq found no passage in our copy addressing the claim attributed to Soccio et al.; the separate pancreas citation is not assessed here. Page numbers were not available in the indexed passages. (LLM, conf=0.78)

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Cited by

Sorted by citations

Authors
Soccio, R. E., Chen, E. R., & Lazar, M. A.
Affiliations
University of Pennsylvania (US)
Corresponding author
Lazar, Mitchell A.
ORCID
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2014-10
Volume
20
Issue
4
Pages
573-591
ISSN
1550-4131 (ISSN-L)
DOI
10.1016/j.cmet.2014.08.005
PMC
PMC4192012
OpenAlex
W2108698393
Cited by
518
References
21
Citations by year
2026: 36 · 2025: 46 · 2024: 37 · 2023: 45 · 2022: 33 · 2021: 60 · 2020: 41 · 2019: 50 · 2018: 70 · 2017: 34 · 2016: 40 · 2015: 26
FWCI
3.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • JPB Foundation
  • National Institutes of Health (5r01dk049780-29)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK 49780, R01-DK049780, K08DK094968, P30DK019525, T32DK007314)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
thiazolidinediones, insulin sensitization, type 2 diabetes, insulin resistance, PPARγ agonism, nuclear receptors, adverse drug reactions, adverse events, glycemic control, personalized treatment
MeSH terms
Animals, Urinary Bladder Neoplasms, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Edema, Humans, Hypoglycemic Agents, Insulin, Thiazolidinediones, PPAR gamma, Fractures, Bone, Non-alcoholic Fatty Liver Disease

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