Fenugreek Compound (N55) Lowers Plasma Glucose through the Enhancement of Response of Physiological Glucagon-like peptide-1.

Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) analogues are approved for treating type 2 diabetes, but are known to activate GLP-1R signaling globally and constitutively. Active compound N55, previously isolated from fenugreek, enhances the potency of GLP-1 without activating GLP-1R. Here we investigated if N55 lowers plasma glucose base on physiological levels of GLP-1.

Isolation of Positive Modulator of Glucagon-like Peptide-1 Signaling from Trigonella foenum-graecum (Fenugreek) Seed.

The glucagon-like peptide-1 receptor (GLP-1R) is expressed in many tissues and has been implicated in diverse physiological functions, such as energy homeostasis and cognition. GLP-1 analogs are approved for treatment of type 2 diabetes and are undergoing clinical trials for other disorders, including neurodegenerative diseases. GLP-1 analog therapies maintain chronically high plasma levels of the analog and can lead to loss of spatiotemporal control of GLP-1R activation.

Modulation of Glucagon-like Peptide-1 (GLP-1) Potency by Endocannabinoid-like Lipids Represents a Novel Mode of Regulating GLP-1 Receptor Signaling.

Glucagon-like peptide-1 (GLP-1) analogs are approved for treatment of type 2 diabetes and are in clinical trials for disorders including neurodegenerative diseases. GLP-1 receptor (GLP-1R) is expressed in many peripheral and neuronal tissues and is activated by circulating GLP-1. Other than food intake, little is known about factors regulating GLP-1 secretion.

Structural basis for calcium and phosphatidylserine regulation of phospholipase C δ1.

Many membrane-associated enzymes, including those of the phospholipase C (PLC) superfamily, are regulated by specific interactions with lipids. Previously, we have shown that the C2 domain of PLC δ1 is required for phosphatidylserine (PS)-dependent enzyme activation and that activation requires the presence of Ca(2+). To identify the site of interaction and the role of Ca(2+) in the activation mechanism, we mutagenized three highly conserved Ca(2+) binding residues (Asp-653, Asp-706, and Asp-708) to Gly in the C2 domain of PLC δ1.