Protein tyrosine phosphatase 1B (PTP1B) is a critical negative modulator of insulin signaling and has attracted considerable attention in treating type 2 diabetes mellitus (T2DM). Low-molecular-weight polymannuronic acid phosphate (LPMP) was found to be a selective PTP1B inhibitor with an IC₅₀ of 1.02 ± 0.17 μM. Cellular glucose consumption was significantly elevated in insulin-resistant HepG2 cells after LPMP treatment. LPMP could alleviate oxidative stress and endoplasmic reticulum stress, which are associated with the development of insulin resistance. Western blot and polymerase chain reaction (PCR) analysis demonstrated that LPMP could enhance insulin sensitivity through the PTP1B/IRS/Akt transduction pathway. Furthermore, animal study confirmed that LPMP could decrease blood glucose, alleviate insulin resistance, and exert hepatoprotective effects in diabetic mice. Taken together, LPMP can effectively inhibit insulin resistance and has high potential as an anti-diabetic drug candidate to be further developed.

The human gut microbiota plays a critical role in the metabolism of dietary carbohydrates. Previous studies have illustrated that marine algae oligosaccharides could be utilized and readily fermented by human gut microbiota. However, the human gut microbiota is classified into three different enterotypes, and how this may affect the fermentation processes of marine algae oligosaccharides has not been studied. Here, using in vitro fermentation and 16 S high-throughput sequencing techniques, we demonstrate that the human gut microbiota has an enterotype-specific effect on the fermentation outcomes of marine algae oligosaccharides. Notably, microbiota with a Bacteroides enterotype was more proficient at fermenting carrageenan oligosaccharides (KOS) as compared to that with a Prevotella enterotype and that with an Escherichia enterotype. Interestingly, the prebiotic effects of marine algae oligosaccharides were also found to be enterotype dependent. Altogether, our study demonstrates an enterotype-specific effect of human gut microbiota on the fermentation of marine algae oligosaccharides. However, due to the availability of the fecal samples, only one sample was used to represent each enterotype. Therefore, our research is a proof-of-concept study, and we anticipate that more detailed studies with larger sample sizes could be conducted to further explore the enterotype-specific prebiotic effects of marine oligosaccharides.