Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: “The Earlier, the Better” in Therapy with Incretin-Based Medicine

Abstract

Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic β-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the β-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of β-cells. However, GLP-1R expression in β-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on β-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of β-cells against glucose toxicity in routine medical care.

Antidiabetic Effects and Enzymatic Antioxidant Activity of Chicken Drumstick Mushroom (Coprinus comatus) Extract in Diabetic Rats Model

“…Furthermore, comatin does not affect GLP-1, and its insulinotropic activity can normally run. 6 C. comatus contains rutin which can increase antioxidant defenses in pancreatic cells and prevent cell damage due to oxidative stress. Rutin activity as antioxidant defense is imperative to prevent deterioration of pancreatic cells, hence the binding of GLP-1 hormone with GLP-1R remains optimal.…”

“…The binding of GLP-1 to its receptors on pancreatic β-cells is decreased, resulting in low secretion and release of insulin hormone while increasing the blood glucose levels. 6 World Health Organization (WHO) has recommended using herbal medicines such as mushrooms. However, research on the activity test as an inhibitor of the DPP-4 enzyme is still scarce.…”

Fixed-ratio Combinations (basal Insulin Plus GLP-1RA) In Type 2 Diabetes. an Analytical Review Of Pivotal Clinical Trials

“…Consequently, the addition of a GLP-1RAs in individuals with some insulin requirement, would allow the use of a lower dose of BIs, with an additional benefit on weight loss, and a lower risk of hypoglycemia [ 21 - 25 ].…”

First-in-Class Oral Semaglutide

“…Long-standing diabetes reduces b-cell mass and requires frequent insulin therapy. [ 68 ] GLP-1Ras bring about improved b-cell function[ 69 ] and reduced b-cell death[ 70 ] with significant HbA1c reduction[ 71 ] and reduced risk of hypoglycaemia. [ 71 ] Efficacy of OS by the duration of diabetes was established in the PIONEER 1, 4, 5 and 8 trials.…”