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Unraveling Insulin Resistance: Mechanism Exploration and Implications
Publish:2025-05-20 Source:ReedBiotech Views:83

Unraveling Insulin Resistance(IR): Mechanism Exploration and Implications

1. Introduction to Insulin

Insulin is an amino acid polypeptide synthesized by pancreatic β-cells, with a molecular weight of 5802 Da, consisting of an α-chain (21 amino acids) and a β-chain (30 amino acids) connected by two disulfide bonds [1][2].

Insulin plays a crucial regulatory role in glucose metabolism, lipid metabolism, and protein metabolism. The following figure illustrates the systemic circulation process of insulin.

 

Figure.1 The systemic circulation process of insulin [3]

2. Insulin Resistance

Insulin resistance(IR) refers to the impaired sensitivity of glucose disposal mediated by insulin levels in the body [4][5]. It is a pathological feature of many clinical disorders, including metabolic diseases like diabetes. As both a pathogenic factor and risk factor, insulin resistance has become a focal point in interdisciplinary research.

Glucose metabolism is essential for maintaining energy homeostasis, with insulin as a key participant. When insulin binds to its receptor, it triggers a cascade involving proteins such as IRS, PI3K, AKT, leading to glycogen storage. Insulin resistance occurs when there is a reduction in insulin receptors, insufficient insulin binding, and impaired GLUT4-mediated glucose transport (see Figure 2 for the metabolic process).

Figure.2 The metabolic process of insulin

(IR: Insulin Receptor Substrate,IR: Insulin Receptor,PI3K: Phosphatidylinositol 3-Kinase,AKT: Serine/Threonine Kinase, GLUT4: Glucose Transporter Type 4,GSV: GLUT4 Storage Vesicle)

3. Evaluation Criteria for Insulin Resistance

The gold standard for assessing insulin resistance is the hyperinsulinemic-euglycemic clamp technique, which offers high accuracy and repeatability. However, its clinical application is limited by high costs and equipment requirements. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) is widely favored due to its simplicity and effectiveness in reflecting insulin resistance. The core formula is:

HOMA-IR=FI(μIU/mL)*FPG(mmol/L)/22.5

where FI is fasting plasma insulin concentration and FPG is fasting blood glucose. Researchers can calculate HOMA-IR using these parameters. Reference values for HOMA-IR are shown in Table 1, noting that thresholds may vary by ethnicity, age, and laboratory (e.g., lower values in Asian populations).

Table .1 Reference values of HOMA-IR for human

Poeple

Reference Range

Clinical significance

Healthy people

1.0

Normal insulin sensitivity

Critical insulin resistance

1.0-1.8

Be alert to the risk of metabolic syndrome

Clarify insulin resistance

1.9

Revealing Insulin Resistance 

Significant insulin resistance

22.5

High risk of diabetes/cardiovascular disease

Note:The threshold values may vary slightly among different races, ages, and laboratories (e.g. Asian populations may have lower thresholds) .The reference values for children and adolescents need to be adjusted according to age.

4.Conversion Between Insulin Concentration and Activity Units

For researchers measuring insulin levels, unit conversion between mass (e.g., mg) and activity (e.g., IU) is essential. According to the WHO (https://nibsc.org), human insulin specifications are:

 

Figure.3​ WHO Website Information on Insulin

According to WHO documentation: 1mIU/L=1μIU/mL=34.7pg/mL​.Given the relative molecular mass of insulin (5802), then 1 mIU/L = 34.7/5.802 ≈6 pmol/L

5.Does Reed Biotech Offer Related Products? 

Reed Biotech provides the following insulin-related ELISA kits:

Catalog No.

Assay Target

Species

RE3153H

Human Insulin (INS) ELISA

Human

RE3153M

Mouse Insulin (INS) ELISA

Mouse

RE3153R

Rat Insulin (INS) ELISA

Rat

Reference

[1]Home PD. Insulin therapy. In: Alberti KGMM, Zimmet P, Defronzo RA editors & Keen H (Hon) editor International Textbook of Diabetes Mellitus (2nd ed) John Wiley & Sons, New York; 1997 p. 899–928.

[2]Dodson G, Steiner D. The role of assembly in insulin’s biosynthesis. Curr Opin Struct Biol. 1998;8:189–94. doi: 10.1016/s0959-440x(98)80037-7.

[3]Victoria L. Tokarz,Patrick E. MacDonald,Amira Klip; The cell biology of systemic insulin function.J Cell Biol2 July 2018; 217 (7): 2273–2289. doi:https://doi.org/10.1083/jcb.201802095

[4]Reaven G. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin North Am. 2004;33:283–303. doi: 10.1016/j.ecl.2004.03.002.

[5]Cefalu WT. Insulin resistance: cellular and clinical concepts. Exp Biol Med (Maywood) 2001;226:13–26. doi: 10.1177/153537020122600103.