IDCC 2301: A Heat-Killed Probiotic Strain with Potential for Blood Glucose Metabolism Support

Maintaining healthy blood glucose levels is closely associated with insulin sensitivity and glucose utilization in peripheral tissues. At the cellular level, the IRS-1/Akt/GLUT4 signaling pathway plays an important role in insulin-mediated glucose uptake, particularly in muscle and adipose tissues.

Emerging research has explored how microbial ingredients, including heat-killed bacteria, may influence metabolic pathways beyond traditional digestive health applications.

In a recently registered Korean patent, ILDONG Bioscience investigated the potential of heat-killed Lactococcus lactis IDCC 2301 to support glucose metabolism. The study evaluated its effects on glucose consumption and insulin signaling in TNF-α-induced insulin-resistant-like 3T3-L1 adipocytes.

1. Study Background: The Relationship Between Inflammation and Insulin Signaling

Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine associated with impaired insulin signaling. Increased TNF-α activity can interfere with the IRS-1/Akt/GLUT4 pathway, potentially reducing glucose uptake by adipocytes.

Three important components of this pathway include:

• IRS-1 (Insulin Receptor Substrate 1): Plays a key role in transmitting insulin signals within cells.

• Akt (Protein Kinase B): Participates in downstream insulin signaling and contributes to the regulation of glucose metabolism.

• GLUT4 (Glucose Transporter 4): Facilitates glucose transport across the cell membrane in response to insulin signaling.

The patent investigated whether heat-killed IDCC 2301 could influence these markers under inflammatory conditions.

2. Experimental Design

The researchers used differentiated 3T3-L1 adipocytes, a widely used cell model for studying adipocyte metabolism.

The experimental procedure included:

• Cell model: Differentiated 3T3-L1 adipocytes

• Inflammatory stimulation: TNF-α at 10 ng/mL

• Test material: Heat-killed bacterial preparations, including IDCC 2301

• Heat-inactivation conditions: 100°C for 30 minutes

• Treatment period: 24 hours

• Evaluation methods: MTT assay, glucose consumption assay, and Western blot analysis

The researchers first assessed cell viability and then examined glucose consumption and changes in proteins involved in insulin signaling.

3. Key Research Findings

Finding 1. No Significant Cytotoxicity Under the Tested Conditions

Cell viability was evaluated using an MTT assay following 24-hour treatment.

• Cell viability remained above 80% in all treatment groups.

• No apparent cytotoxicity was observed under the experimental conditions.

• The results supported the use of the selected treatment conditions for subsequent metabolic evaluations.

Finding 2. Increased Apparent Glucose Consumption

The researchers measured the residual glucose concentration in the culture medium after treatment.

TNF-α stimulation increased the amount of glucose remaining in the culture medium, indicating reduced glucose consumption by the adipocytes.

In contrast, treatment with heat-killed bacterial preparations reduced the residual glucose concentration compared with the TNF-α-only group.

At a concentration of 5 × 10⁶ cells/mL, the reported increases in apparent glucose consumption were:

Test material	Increase in apparent glucose consumption
TH	22.8%
IDCC 2301 (LLA)	23.7%
RH	19.0%

Among the three tested preparations, IDCC 2301 showed the highest increase in apparent glucose consumption. Based on this result, IDCC 2301 was selected for further investigation of the IRS-1/Akt/GLUT4 signaling pathway.

Finding 3. Recovery of GLUT4 Protein Expression

GLUT4 is an important glucose transporter involved in insulin-responsive glucose uptake.

The researchers observed that TNF-α stimulation reduced GLUT4 expression to 49.7% of the untreated control level.

Following treatment with heat-killed IDCC 2301, GLUT4 expression increased to 125.2% of the untreated control level.

This result suggests that IDCC 2301 may help restore GLUT4 expression under TNF-α-induced inflammatory conditions in the adipocyte model.

Finding 4. Reduction in IRS-1 Ser307 Phosphorylation

Increased phosphorylation of IRS-1 at Ser307 is associated with impaired insulin signaling in certain inflammatory conditions.

The study reported the following changes in the p-IRS-1 Ser307/IRS-1 ratio:

• Untreated control: Reference level of 100%

• TNF-α-treated group: Increased to 165.9%

• IDCC 2301-treated group: Reduced to 105.3%

The reduction observed following IDCC 2301 treatment indicates a shift toward the baseline level of IRS-1 Ser307 phosphorylation.

Finding 5. Recovery of Akt Phosphorylation

Akt is a downstream signaling protein involved in insulin-mediated metabolic regulation.

The p-Akt/Akt ratio decreased to 64.5% of the untreated control level following TNF-α stimulation.

In the IDCC 2301-treated group, this ratio increased to 93.6%.

This finding suggests that IDCC 2301 may help restore Akt-related signaling activity under the experimental conditions.

4. Summary of the Main Findings

The patent presents several complementary observations related to glucose metabolism and insulin signaling.

Evaluation parameter	TNF-α-induced change	Response following IDCC 2301 treatment
Apparent glucose consumption	Decreased	Increased by 23.7%
GLUT4 expression	Decreased to 49.7%	Recovered to 125.2%
p-IRS-1 Ser307/IRS-1 ratio	Increased to 165.9%	Reduced to 105.3%
p-Akt/Akt ratio	Decreased to 64.5%	Recovered to 93.6%

Note: Protein expression and phosphorylation values are expressed relative to the untreated control, while the glucose consumption result represents the reported increase compared with the TNF-α-treated group.

Taken together, these results indicate that heat-killed IDCC 2301 influenced multiple markers associated with insulin signaling and glucose utilization in the tested adipocyte model.

5

. Potential Applications in Metabolic Health

One notable aspect of this research is its focus on a heat-killed bacterial preparation rather than relying exclusively on viable probiotic cells.

Heat-killed microbial ingredients can offer formulation flexibility because their application does not depend on maintaining bacterial viability throughout product storage.

The findings also provide a scientific basis for further investigating IDCC 2301 in the context of metabolic health and glucose metabolism.

Potential product development areas include:

• Metabolic health supplements

• Blood glucose management-oriented ingredient concepts

• Heat-killed probiotic and postbiotic formulations

• Capsules, tablets, powders, and other food formats

However, the present findings are based on a cell-based experimental model. Human clinical studies will be necessary to determine whether the observed cellular responses translate into measurable improvements in blood glucose regulation in consumers.

Conclusion

The patent research demonstrates the potential of heat-killed Lactococcus lactis IDCC 2301 as a microbial ingredient for further investigation in glucose metabolism.

In TNF-α-induced 3T3-L1 adipocytes, IDCC 2301 increased apparent glucose consumption by 23.7%. It also influenced key components of the insulin signaling pathway, including GLUT4 expression, IRS-1 Ser307 phosphorylation, and Akt phosphorylation.

These findings provide a foundation for exploring strain-specific postbiotic applications in metabolic health.

At ILDONG Bioscience, we continue to investigate the functional properties of strain-specific microbial ingredients, expanding scientific research into new application areas beyond traditional probiotic formulations.

Patent Reference: Korean Patent No. 10-3036042, Composition and Health Functional Food Containing Lactococcus lactis IDCC 2301 Effective in Lowering Blood Glucose.