The Role of Protein Tyrosine Phosphatase (PTP)-1B in Cardiovascular Disease and Its Interplay with Insulin Resistance

Abstract

Endothelial dysfunction is a key feature of cardiovascular disorders associated with obesity and diabetes. Several studies identified protein tyrosine phosphatase (PTP)-1B, a member of the PTP superfamily, as a major negative regulator for insulin receptor signaling and a novel molecular player in endothelial dysfunction and cardiovascular disease. Unlike other anti-diabetic approaches, genetic deletion or pharmacological inhibition of PTP1B was found to improve glucose homeostasis and insulin signaling without causing lipid buildup in the liver, which represents an advantage over existing therapies. Furthermore, PTP1B was reported to contribute to cardiovascular disturbances, at various molecular levels, which places this enzyme as a unique single therapeutic target for both diabetes and cardiovascular disorders. Synthesizing selective small molecule inhibitors for PTP1B is faced with multiple challenges linked to its similarity of sequence with other PTPs; however, overcoming these challenges would pave the way for novel approaches to treat diabetes and its concurrent cardiovascular complications. In this review article, we summarized the major roles of PTP1B in cardiovascular disease with special emphasis on endothelial dysfunction and its interplay with insulin resistance. Furthermore, we discussed some of the major challenges hindering the synthesis of selective inhibitors for PTP1B.

Antidiabetic Potential of Marine Brown Algae—a Mini Review

“…Similar phlorotannins were isolated from the methanol extract of Ecklonia stolonifera reported to possess an inhibitory activity against α-glucosidase enzymes which was attributed to the presence of phlorofucofuroeckol-A, dieckol, and 7-phloroeckol [29]. Furthermore, among the isolated phlorotannins, phlorofucofuroeckol-A (IC 50 : 1.37 μM) and dieckol (IC 50 : 1.61 μM) were found as the most effective inhibitors against the α-glucosidase enzyme compared to the reference drug acarbose (IC 50 : 51.65 μM) [20]. The phlorotannin eckol (IC 50 : 11.16 μM) isolated from Ecklonia maxima exhibited the potent α-glucosidase inhibitory activity compared to the phloroglucinol (IC 50 : 1991 μM) [20].…”

“…Protein tyrosine phosphatase 1B (PTP 1B) is another enzyme which is involved in the insulin signalling pathway and located on the cytoplasmic face of the endoplasmic reticulum. [20]. PTP 1B enzyme is a negative regulator of the tyrosine phosphorylation cascade which is directly involved with the insulin signalling pathway.…”

“…Furthermore, among the isolated phlorotannins, phlorofucofuroeckol-A (IC 50 : 1.37 μM) and dieckol (IC 50 : 1.61 μM) were found as the most effective inhibitors against the α-glucosidase enzyme compared to the reference drug acarbose (IC 50 : 51.65 μM) [20]. The phlorotannin eckol (IC 50 : 11.16 μM) isolated from Ecklonia maxima exhibited the potent α-glucosidase inhibitory activity compared to the phloroglucinol (IC 50 : 1991 μM) [20]. Similarly, fucofuroeckol-A and dioxinodehydroeckol isolated from Ecklonia bicyclis were also reported to have an inhibitory effect on α-amylase and α-glucosidase enzymes [20].…”

“…The phlorotannin eckol (IC 50 : 11.16 μM) isolated from Ecklonia maxima exhibited the potent α-glucosidase inhibitory activity compared to the phloroglucinol (IC 50 : 1991 μM) [20]. Similarly, fucofuroeckol-A and dioxinodehydroeckol isolated from Ecklonia bicyclis were also reported to have an inhibitory effect on α-amylase and α-glucosidase enzymes [20]. Moreover, a significant reduction of the postprandial blood glucose level was observed by the isolated phlorotannins, dieckol, and diphlorethohydroxycarmalol in both normal and diabetesinduced mouse groups [29].…”

“…In addition to the Ecklonia species, brown seaweeds belong to the genus Eisenia also possess strong antidiabetic activity by inhibiting α-amylase and α-glucosidase enzymes [30]. Eckol, dieckol, and 7-phloroeckol isolated from Eisenia [20]. Ishige okamurae is a marine brown alga that belongs to the family Ishigeaceae and reported to have a potent antidia-betic activity through the mechanism of α-amylase and αglucosidase inhibition.…”