L-isoleucine works synergistically with insulin

L-isoleucine, an essential amino acid, exhibits synergistic effects with insulin in diabetes treatment, primarily manifested in the following aspects:

I. Promotion of Insulin Secretion

Stimulating Pancreatic β Cells

L-isoleucine acts on pancreatic β cells by activating relevant membrane receptors, triggering a series of intracellular signaling pathways such as the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. Activation of these pathways enhances insulin synthesis and secretion, aiding in blood glucose reduction. When blood L-isoleucine levels rise, pancreatic β cells become more sensitive to glucose, enabling timely and effective insulin secretion in response to elevated blood sugar, thus improving glycemic regulation.

Enhancing Glucose-Stimulated Insulin Release

In diabetic patients, pancreatic β cells often show reduced responsiveness to glucose stimulation. When L-isoleucine acts in conjunction with glucose, it enhances glucose uptake and metabolism in β cells, further promoting insulin release. This synergistic effect improves insulin secretion efficiency, allowing blood glucose to return to normal levels more rapidly.

II. Improvement of Insulin Sensitivity

Regulation of Intracellular Signaling

L-isoleucine influences intracellular insulin signaling pathways, enhancing downstream signaling after insulin binds to its receptor. It activates insulin receptor substrate (IRS) proteins, promotes phosphatidylinositol-3-kinase (PI3K) activation, and subsequently triggers downstream molecules like protein kinase B (Akt). Activation of these molecules promotes the translocation of glucose transporter 4 (GLUT4) to the cell membrane, increasing glucose uptake and utilization, thereby alleviating insulin resistance and enhancing insulin sensitivity.

Regulation of Metabolism-Related Gene Expression

L-isoleucine also improves insulin sensitivity by regulating the expression of metabolism-related genes. For example, it upregulates genes involved in glucose and lipid metabolism, promoting cellular glucose uptake and utilization while inhibiting fat synthesis and inflammatory responses to reduce insulin resistance.

III. Reduction of Inflammatory Responses Associated with Insulin Resistance

Inhibition of Inflammatory Signaling Pathways

Diabetic patients often suffer from chronic low-grade inflammation, which contributes to the development of insulin resistance. L-isoleucine inhibits the activation of inflammatory signaling pathways such as the nuclear factor-κB (NF-κB) pathway. As a key transcription factor in inflammation, NF-κB’s activation is suppressed by L-isoleucine, reducing the production and release of inflammatory cytokines and mitigating the impact of inflammation on insulin sensitivity.

Regulation of Immune Cell Function

L-isoleucine modulates immune cell function by inhibiting the activation and infiltration of inflammatory cells. It influences macrophage polarization, promoting the shift toward anti-inflammatory M2 macrophages while reducing the number and activity of pro-inflammatory M1 macrophages. This immunomodulatory effect helps improve insulin resistance and enhance insulin therapy efficacy.

IV. Synergistic Reduction of Blood Glucose Fluctuations

Stabilization of Blood Glucose Levels

The synergistic action of L-isoleucine and insulin provides more stable glycemic control and reduces blood glucose fluctuations. While insulin primarily lowers blood glucose by promoting glucose uptake and utilization, its 单独使用 (sole use) may cause rapid blood glucose decline or hypoglycemia. L-isoleucine gradually and continuously reduces blood glucose through its own metabolism and regulation of other metabolic pathways, complementing insulin’s effects to maintain more stable blood glucose levels.

Delayed Gastric Emptying

L-isoleucine also slows gastric emptying, prolonging food retention in the gastrointestinal tract and reducing the absorption rate of carbohydrates. This effect complements insulin’s glucose-lowering action, helping to better control postprandial blood glucose spikes and minimizing damage from blood glucose fluctuations.