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Cited by 1,258Adipokines, Inflammation, and Metabolic DiseasesDiabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and Cancer

Insulin action and resistance in obesity and type 2 diabetes

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Czech, Michael P·2017·Nature Medicine
DOI 10.1038/nm.4350PMC PMC6048953
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Abstract

Nutritional excess is a major forerunner of type 2 diabetes. It enhances the secretion of insulin, but attenuates insulin's metabolic actions in the liver, skeletal muscle and adipose tissue. However, conflicting evidence indicates a lack of knowledge of the timing of these events during the development of obesity and diabetes, pointing to a key gap in our understanding of metabolic disease. This Perspective reviews alternate viewpoints and recent results on the temporal and mechanistic connections between hyperinsulinemia, obesity and insulin resistance. Although much attention has addressed early steps in the insulin signaling cascade, insulin resistance in obesity seems to be largely elicited downstream of these steps. New findings also connect insulin resistance to extensive metabolic cross-talk between the liver, adipose tissue, pancreas and skeletal muscle. These and other advances over the past 5 years offer exciting opportunities and daunting challenges for the development of new therapeutic strategies for the treatment of type 2 diabetes.

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Authors
Czech, M. P.
Affiliations
University of Massachusetts Chan Medical School (US)
Corresponding author
Czech, Michael P
ORCID
Czech, Michael P
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2017-07
Volume
23
Issue
7
Pages
804-814
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.4350
PMC
PMC6048953
OpenAlex
W2736294384
Cited by
1,258
References
19
Citations by year
2026: 94 · 2025: 107 · 2024: 130 · 2023: 173 · 2022: 175 · 2021: 226 · 2020: 160 · 2019: 113 · 2018: 69 · 2017: 10
FWCI
12.76
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK030898, R01DK103047, R37DK030898, R01DK085753)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
insulin resistance, hyperinsulinemia, obesity, type 2 diabetes, overfeeding, high-fat diet, insulin signaling, metabolic crosstalk, liver, adipose tissue, skeletal muscle, pancreas, insulin secretion
MeSH terms
Adipose Tissue, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Liver, Obesity, Signal Transduction, Muscle, Skeletal, Metabolic Syndrome, Insulin-Secreting Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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