Pediococcus acidilactici pA1c® Improves the Beneficial Effects of Metformin Treatment in Type 2 Diabetes by Controlling Glycaemia and Modulating Intestinal Microbiota
Introduction
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, mainly characterized by an increase in blood glucose concentration produced by deficient insulin secretion by the β-cells of the pancreatic islets in the context of insulin resistance. This disease affects more than 90% of diabetic patients and continues to increase globally, being driven by factors such as an unhealthy diet and a sedentary lifestyle. Metformin is generally prescribed as standard treatment for the disease, due to its remarkable ability to lower plasma glucose levels and improve insulin sensitivity. Recently, it has been investigated how metformin influences the intestinal microbiota, favoring glucose homeostasis and improving the lipid profile. However, its exact mechanism remains unclear.
On the other hand, a relationship between glycemic imbalances and intestinal dysbiosis has been shown to exist. In previous studies, the probiotic Pediococcus acidilactici pA1c® has been shown to improve insulin resistance and protect intestinal health in models of high-fat diet (HFD)-induced T2DM. In this research it has been analyzed whether the combination of metformin with pA1c® could improve the anti-diabetic effects of the probiotic. For this purpose, the protective effect of metformin and pA1c®, as well as the combination of both, was tested in a mouse model with HFD-induced T2DM. The results suggest that the combination of treatments could offer new therapeutic approaches for type 2 diabetes.
The role of GLP-1, leptin and C-peptide in this study
GLP-1 is an incretin hormone that is produced mainly in the intestine in response to food intake, and whose function is to stimulate insulin production and decrease glucagon production. In addition, it also delays gastric emptying and generates a feeling of satiety. In other studies it is mentioned that metformin can increase the release of GLP-1. However, in the present study no significant results were observed, even in animals treated only with metformin.
Leptin is a cytokine produced mainly by adipocytes and plays a crucial role in the regulation of energy balance and appetite control. In type 2 diabetes, leptin resistance is a common phenomenon, which hinders weight loss and appetite control. In the present investigation, much higher leptin levels were observed in treated animals compared to control animals. In addition, the latter suffered weight gain, despite no differences in food intake, suggesting that both treatments separately and especially the combination of pA1c® and metformin could lead to improved leptin sensitivity and, therefore, less fat deposition.
Finally, C-peptide is a fragment produced during insulin synthesis in the pancreas. When insulin is produced, proinsulin splits into two parts: insulin and C-peptide. Measurement of blood C-peptide levels is useful for assessing beta-pancreatic function and endogenous insulin production. In patients with type 2 diabetes, beta-pancreatic function is impaired, resulting in decreased insulin production. In the present study, C-peptide levels are observed to be significantly increased in patients treated with both pA1c® and Met + pA1c®, suggesting that the probiotic could lead to changes in insulin metabolism. However, metformin alone did not modify C-peptide concentrations at the end of the study.
ELISA kits for GLP-1, leptin and C-peptide quantification
Differences in GLP-1, leptin and C-peptide expression in both treated and control animals were observed using ELISA kits from Abyntek Research Reagents. Specifically, the ELISA Kit for C-Peptide (CP, ABK1-E7035), ELISA Kit for Leptin (LEP, ABK1-E1177) and ELISA Kit for Glucagon Like Peptide 1 (GLP1, ABK1-E7276) were used. This made it possible to observe the effects of the different treatments in relation to glucose regulation, pancreatic function, insulin resistance and lipid metabolism in the high-fat diet-induced type 2 diabetes model.
Once again, scientists rely on Abyntek Research Reagents, Abyntek Biopharma’s proprietary product line, to conduct their research.
Conclusion
This study demonstrates that the probiotic P. acidilactici can improve the therapeutic effects of metformin in patients with type 2 diabetes. The results obtained reveal that the probiotic not only helps to control glycemia, but also modulates the intestinal microbiota, favoring a healthier metabolic profile. In this context, although no increase in GLP-1 levels is observed, pA1c® improves leptin sensitivity, decreasing fat deposition, and favors C-peptide secretion, indicating improved insulin function. These findings suggest that the combination of P. acidilactici with metformin could have synergistic effects, optimizing the management of type 2 diabetes by improving both glucose regulation and metabolism at the intestinal and systemic levels.
This article was published in Pharmaceutics on April 10, 2023.
