Next Article in Journal
Mechanisms of the Cytotoxic Effect of Selenium Nanoparticles in Different Human Cancer Cell Lines
Previous Article in Journal
Role of Methylation in Period2 (PER2) Transcription in the Context of the Presence or Absence of Light Signals: Natural and Chemical—Studies on the Pig Model
Previous Article in Special Issue
β Cell GHS-R Regulates Insulin Secretion and Sensitivity
Review

Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

Department of internal Medicine, Division of Endocrinology, Erasmus Medical Center, 40, 3015 GD Rotterdam, The Netherlands
Academic Editor: Maria Elisabeth Street
Int. J. Mol. Sci. 2021, 22(15), 7797; https://doi.org/10.3390/ijms22157797
Received: 16 June 2021 / Revised: 11 July 2021 / Accepted: 13 July 2021 / Published: 21 July 2021
(This article belongs to the Special Issue Insulin Sensitivity/Resistance: From Physiology to Disease)
For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases. View Full-Text
Keywords: hyperinsulinemia; insulin resistance; insulin secretion; insulin clearance; growth hormone; insulin-like growth factor-I; obesity; diabetes; cardiovascular disease; cancer; longevity hyperinsulinemia; insulin resistance; insulin secretion; insulin clearance; growth hormone; insulin-like growth factor-I; obesity; diabetes; cardiovascular disease; cancer; longevity
Show Figures

Figure 1

MDPI and ACS Style

Janssen, J.A.M.J.L. Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer. Int. J. Mol. Sci. 2021, 22, 7797. https://doi.org/10.3390/ijms22157797

AMA Style

Janssen JAMJL. Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer. International Journal of Molecular Sciences. 2021; 22(15):7797. https://doi.org/10.3390/ijms22157797

Chicago/Turabian Style

Janssen, Joseph A.M.J.L. 2021. "Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer" International Journal of Molecular Sciences 22, no. 15: 7797. https://doi.org/10.3390/ijms22157797

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop