ArticleJournal of the Royal Society, Interface2014
Raison d'être of insulin resistance: the adjustable threshold hypothesis.
Article in Journal of the Royal Society, Interface, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed.
- Interplay between obesity-associated insulin resistance and immune system through the lens of evolutionary medicine.Molecular metabolism · 2026Review
- The effects of obesity on thyroid function in a metabolically healthy high-fat, high-carbohydrate diet-induced obese rat model.Frontiers in endocrinology · 2025Article
- Establishing a Female Animal Model of Prediabetes Using a High-Carbohydrate, High-Fat Diet.Current issues in molecular biology · 2024Article
- Article
- Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey.Journal of computational neuroscience · 2022Article
- The role of Aβ in Alzheimer's Disease as an Evolutionary Outcome of Optimized Innate Immune Defense.The journal of prevention of Alzheimer's disease · 2022Article
- A glucose-insulin-glucagon coupled model of the isoglycemic intravenous glucose infusion experiment.Frontiers in physiology · 2022Article
- Aquaporins in insulin resistance and diabetes: More than channels!Redox biology · 2021Review
- Type 2 diabetes: one disease, many pathways.American journal of physiology. Endocrinology and metabolism · 2020Article
- Body Mass Dynamics Is Determined by the Metabolic Ohm's Law and Adipocyte-Autonomous Fat Mass Homeostasis.iScience · 2020Article
- Type 3 Diabetes and Its Role Implications in Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Uric acid and cardiometabolic diseases.Clinical hypertension · 2020Review
- Adenine nucleotide-mediated regulation of hepatic PTP1B activity in mouse models of type 2 diabetes.Diabetologia · 2019Article
- Associations of insulin resistance with cognition in individuals without diagnosed diabetes: Results from the Hispanic Community Health Study/Study of Latinos.Diabetes research and clinical practice · 2019Article
- DPP-4 Inhibitors as Potential Candidates for Antihypertensive Therapy: Improving Vascular Inflammation and Assisting the Action of Traditional Antihypertensive Drugs.Frontiers in immunology · 2019Review
- Dissipative structures in biological systems: bistability, oscillations, spatial patterns and waves.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2018Review
- The interrelation of osteoarthritis and diabetes mellitus: considering the potential role of interleukin-10 and in vitro models for further analysis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Review
- Rebound Feeding in the Wake of Short-Term Suspension of Food Intake Differs in the Presence of Estrous Cycle Peak versus Nadir Levels of Estradiol.Endocrinology and metabolism (Seoul, Korea) · 2017Article
- The association between Alu hypomethylation and severity of type 2 diabetes mellitus.Clinical epigenetics · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epidemics of obesity and diabetes demand a deeper understanding of insulin resistance, for which the adjustable threshold hypothesis is formed in this paper. To test the hypothesis, mathematical modelling was used to analyse clinical data and to simulate biological processes at both molecular and organismal levels. I found that insulin resistance roots in the thresholds of the cell's bistable response. By assuming heterogeneity of the thresholds, single cells' all-or-none response can collectively produce a graded response at the whole-body level-conforming to existing data. The thresholds have to be adjustable to adapt to extreme conditions. During pregnancy, for example, the thresholds increase consistently to strengthen the mother's insulin resistance to meet the increasing glucose demand of the expanding fetal brain. I also found that hysteresis, a key element of the adjustable threshold hypothesis, can explain reactive hypoglycaemia, which is characteristic of diabetes complications but remains poorly understood. Contrary to the common belief that insulin promotes glucose disposal, the results imply that insulin is the body's 'ration stamp' to restricting glucose utilization by peripheral tissues and that insulin resistance is primarily a well-evolved mechanism. The hypothesis provides an intuitive and dynamical description of the previously formless insulin resistance, which may make the detection of pre-diabetes possible and may shed light on the optimal timing of therapeutic intervention. It also provides valuable clues to defining subtypes of type 2 diabetes that might respond differently to specific prevention and intervention strategies.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.