Grape powder attenuates the negative effects of GLP-1 receptor antagonism by exendin-3 (9–39) in a normoglycemic mouse model

Abstract

Prediabetes is a condition affecting 35% of US adults and about 50% of US adults age 65+. Foods rich in polyphenols, including flavanols and other flavonoids, have been studied for their putative beneficial effects on many different health conditions including type 2 diabetes mellitus and prediabetes. Studies have shown that some flavanols increase glucagon-like peptide 1 (GLP-1) secretion. GLP-1 is a feeding hormone that increases insulin secretion after carbohydrate consumption, and increased GLP-1 secretion may be responsible for some of the beneficial effects on glycemic control after flavanol consumption. The present study explored the effects of grape powder consumption on metrics of glycemic health in normoglycemic and prediabetic C57BL/6J mice; additionally, the mechanism of action of grape powder polyphenols was investigated. Grape powder significantly reduced (p < 0.01) blood glucose levels following oral glucose gavage after GLP-1 receptor antagonism by exendin-3 (9-39) compared to sugar-matched control, indicating that it was able to attenuate the hyperglycemic effects of GLP-1 receptor antagonism. Grape powder was employed in acute (1.6 g grape powder per kg bodyweight) and long-term high fat diet (grape powder incorporated into treatment diets at 5% w/w) feeding studies in normoglycemic and prediabetic (diet-induced obesity) mice; grape powder did not impove glycemic control in these studies versus sugar-matched control. The mechanisms by which grape powder ameliorates the deleterious effects of GLP-1 receptor antagonism warrant further study.

Therapeutic effect of berberine on renal ischemia-reperfusion injury in rats and its effect on Bax and Bcl-2

“…Studies have shown that this drug has promising therapeutic effects in the treatment of digestive diseases and diarrhea, but its absorption through oral administration is not satisfactory, and the duration of plasma concentration is short (6,7). Exendin-(9–39), as an antagonist of GLP-1R, can effectively attenuate Nesfatin-1 and delay the emptying of the stomach and reduce the intake of berberine and effectively maintain the retention of berberine (8). In recent years, it has been found that berberine has anti-inflammatory functions and more and more studies confirmed that berberine played a certain regulatory role in inhibiting the body's immune response and anti-apoptosis response (9).…”

Daily replacement of very high-fat diet stabilizes food intake and improves mouse welfare by ensuring food quality

“…Since VHFD contains 35% (w/w) fat (see S1 Table ), we reasoned that lipid oxidation could also decrease VHFD palatability and intake. Others have suggested that oxidation of VHFD may occur and that it should avoided [ 5 , 6 ], but this hypothesis has not yet been thoroughly investigated.…”

“…may occur and that it should avoided [5,6], but this hypothesis has not yet been thoroughly investigated.…”

“…How storage and handling conditions of VHFD impact experimental outcome could be related to food quality. A few researchers have speculated that the quality of VHFD may be reduced from spoilage by lipid oxidation and that this can be avoided by replacing food weekly [ 4 ] or 2–3 times weekly [ 5 , 6 ]. But, there is no evidence that such practices ensure the quality of VHFD.…”