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Metabolites
Special Issues
Insulin Clearance and Metabolic Dysregulation in Health and Disease
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Insulin Clearance and Metabolic Dysregulation in Health and Disease

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 1054

Special Issue Editors

Dr. Morvarid Kabir

E-Mail Website
Guest Editor
Department of Medicine, Diabetes and Aging Center, Los Angeles, CA 90048, USA
Interests: adipose tissue; obesity; type 2 diabetes; insulin resistance; lipid metabolism
Special Issues, Collections and Topics in MDPI journals
Dr. Richard N. Bergman

E-Mail Website
Guest Editor
Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Interests: fatty acids; lipid molecules; type 2 diabetes; insulin resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the past decade, studies have highlighted the significant role of insulin clearance in obesity and the pathogenesis of Type 2 diabetes. It has been established that diminished hepatic insulin clearance results in elevated levels of insulin in the systemic circulation, consequently leading to hyperinsulinemia. Prolonged hyperinsulinemia can further impair the function of beta cells, ultimately driving the progression of Type 2 diabetes. However, the precise mechanisms that underlie the relationship between insulin clearance, metabolic dysfunction, and the pathogenesis of Type 2 diabetes remain poorly defined.

This Special Issue aims to present recent data and insights into the interplay between insulin clearance and metabolic dysfunction in health and disease. The scope of this Special Issue includes investigations in both animal models and human subjects, alongside innovative approaches such as lipidomics, metabolomics, and the discovery of biomarkers that identify changes linked to altered insulin clearance and broader metabolic pathways. This collection provides a comprehensive exploration of the critical mechanisms that contribute to obesity, insulin resistance, and Type 2 diabetes, advancing our understanding of their role in metabolic health.

Dr. Morvarid Kabir
Dr. Richard N. Bergman
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • insulin clearance
  • insulin resistance
  • type 2 diabetes
  • obesity
  • hyperinsulinemia
  • metabolic dysfunction

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Published Papers (1 paper)

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Research

14 pages, 1920 KB  
Article
Determinants of Glucose Tolerance in a Population Without Overt Diabetes: The Role of β-Cell Glucose Sensitivity, Insulin Sensitivity, and Insulin Clearance
by Beatrice Marelli, Andrea Foppiani, Federica Sileo, Giorgia Pozzi, Silvia Gallosti, Chiara Cappellini, Andrea Mari, Simona Bertoli and Alberto Battezzati
Metabolites 2026, 16(4), 218; https://doi.org/10.3390/metabo16040218 - 26 Mar 2026
Viewed by 502
Abstract
Background/Objectives: To investigate how β-cell glucose sensitivity, insulin clearance, and insulin sensitivity interact to determine glucose tolerance in a population without overt diabetes. Methods: We analyzed data from 54 individuals without diabetes (age: 44 years, IQR: 27–56; 63% females; BMI: 24.5 [...] Read more.
Background/Objectives: To investigate how β-cell glucose sensitivity, insulin clearance, and insulin sensitivity interact to determine glucose tolerance in a population without overt diabetes. Methods: We analyzed data from 54 individuals without diabetes (age: 44 years, IQR: 27–56; 63% females; BMI: 24.5 kg/m2, IQR: 21.9–28.7; HbA1c 33.26 mmol/mol, IQR: 32.13–35.51) undergoing a 3-h OGTT. β-cell glucose sensitivity, insulin clearance, and insulin sensitivity were assessed via modeling of OGTT data. Their relationship with glucose tolerance was evaluated through linear regression models. Results: β-cell glucose sensitivity strongly predicted glucose tolerance during the OGTT (IQR increase effect: −87 mg/dL; 95% CI: −141, −32; p = 0.003) but not fasting glucose (p = 0.4). Patients with lower β-cell glucose sensitivity showed the widest range of glucose tolerance during the OGTT, some approaching diabetic levels whereas others tolerating glucose well; insulin sensitivity was the strongest determinant of this variance (IQR increase effect: −49 mg/dL; 95% CI: −68, −31; p < 0.001) significantly influencing the relationship between β-cell glucose sensitivity and glucose tolerance (interaction term p = 0.035). Conversely, insulin clearance did not show a statistically significant association with mean glucose levels during the OGTT (β: 4.2; 95% CI: −8.0, 16; p = 0.5). However, a non-linear relationship between insulin clearance and β-cell glucose sensitivity was identified, and three distinct metabolic subgroups were defined, highlighting the heterogeneity underlying the development of dysglycemia. Conclusions: β-cell glucose sensitivity is the primary determinant of glucose tolerance during an oral glucose challenge. While high β-cell glucose sensitivity often overcomes low insulin sensitivity, the latter becomes crucial when β-cell glucose sensitivity is low. The identification of distinct metabolic profiles, related to insulin secretion and clearance, highlights the heterogeneity of the transition from glucose tolerance to dysglycemia. Full article
(This article belongs to the Special Issue Insulin Clearance and Metabolic Dysregulation in Health and Disease)
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