Multiorgan insulin sensitivity in lean and obese subjects
Open accessAbstract
OBJECTIVE: To provide a comprehensive assessment of multiorgan insulin sensitivity in lean and obese subjects with normal glucose tolerance. RESEARCH DESIGN AND METHODS: The hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 ± 0.6 kg/m2, mean ± SEM) and 26 lean (22.5 ± 0.3 kg/m2) subjects with normal glucose tolerance. Insulin was infused at different rates to achieve low, medium, and high physiological plasma concentrations. RESULTS: In obese subjects, palmitate and glucose Ra in plasma decreased with increasing plasma insulin concentrations. The decrease in endogenous glucose Ra was greater during low-, medium-, and high-dose insulin infusions (69 ± 2, 74 ± 2, and 90 ± 2%) than the suppression of palmitate Ra (52 ± 4, 68 ± 1, and 79 ± 1%). Insulin-mediated increase in glucose disposal ranged from 24 ± 5% at low to 253 ± 19% at high physiological insulin concentrations. The suppression of palmitate Ra and glucose Ra were greater in lean than obese subjects during low-dose insulin infusion but were the same in both groups during high-dose insulin infusion, whereas stimulation of glucose Rd was greater in lean than obese subjects across the entire physiological range of plasma insulin. CONCLUSIONS: Endogenous glucose production and adipose tissue lipolytic rate are both very sensitive to small increases in circulating insulin, whereas stimulation of muscle glucose uptake is minimal until high physiological plasma insulin concentrations are reached. Hyperinsulinemia within the normal physiological range can compensate for both liver and adipose tissue insulin resistance, but not skeletal muscle insulin resistance, in obese people who have normal glucose tolerance.
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Postprandial insulin excursions drive glucose disposal through actions in muscle and adipose tissue, and GIP enhances insulin sensitivity and glucose disposal in adipose tissue.
“Postprandial excursions of insulin drive glucose dis posal through actions in muscle and adipose tissue, along with effects of postprandial excursions in GIP, to enhance insulin sensitivity and augment glucose disposal in adipose tissue (2-5).”
From Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test (2024) · cites this paper as [4]
The Conclusions (page unavailable) describe insulin concentrations simulating postprandial conditions and report insulin-stimulated muscle glucose uptake and suppression of adipose-tissue lipolysis. The Results (page unavailable) also report increased glucose disposal with insulin infusion. The paper does not establish adipose-tissue glucose disposal or the claimed effects of GIP; a search for GIP found no relevant passage. (LLM, conf=0.87)
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References 30 · Cited by 99
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- Authors
- Conte, C., Fabbrini, E., Kars, M., Mittendorfer, B., Patterson, B. W., & Klein, S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Klein, Samuel
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2012-05-11
- Volume
- 35
- Issue
- 6
- Pages
- 1316-1321
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC3357234
- OpenAlex
- W1994250078
- Cited by
- 99
- References
- 30
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 3 · 2022: 17 · 2021: 9 · 2020: 8 · 2019: 11 · 2018: 10 · 2017: 5 · 2016: 5 · 2015: 1 · 2014: 5 · 2013: 5 · 2012: 3
- FWCI
- 3.59
- 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)
- Research Publications (Maastricht University) (publishedVersion, cc-by-nc-nd)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (5p41rr000954-34, UL1TR000448)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK37948, DK56341, R01DK037948, P30DK056341, P30DK020579)
- National Center for Research Resources (P41-RR000954, RR 00954, UL1RR024992)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- insulin sensitivity, obesity, hyperinsulinemic-euglycemic clamp, endogenous glucose production, adipose tissue lipolysis, skeletal muscle glucose uptake, insulin resistance, normal glucose tolerance, hyperinsulinemia, glucose tracer
- MeSH terms
- Adipose Tissue, Adult, Blood Glucose, Fatty Liver, Female, Humans, Insulin, Insulin Resistance, Lipolysis, Liver, Male, Middle Aged, Obesity, Triglycerides, Glucose Clamp Technique, Body Mass Index, Muscle, Skeletal, Dyslipidemias, Sedentary Behavior, Non-alcoholic Fatty Liver Disease
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