Experiments on adult Wistar rats with streptozotocin-induced diabetes showed that antihyperglycemic activity of an original nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is more pronounced under conditions of oral application than after intraperitoneal injection. These data provided a basis for studying the effect of Noopept on major indexes of the incretin system. Streptozotocin was shown to decrease the concentrations of incretin GLP-1 and insulin in the blood. Noopept had a normalizing effect on these parameters. This influence of Noopept was not related to the inhibition of a major enzyme metabolizing incretins (dipeptidyl peptidase IV). A reference drug sitagliptin also increased the contents of incretins and insulin, which was associated with the inhibition of dipeptidyl peptidase IV. It is known that GLP-1 increases NGF expression in the insular system. Our results suggest that the increase in incretin activity contributes to the antiapoptotic effect of Noopept on pancreatic β cells. The mechanism for an increase in blood GLP-1 level after oral application of Noopept requires further investigations.
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JCI Insight
December 2024
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, University of Toronto, Toronto, Canada.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived peptide hormones that potentiate glucose-dependent insulin secretion. The clinical development of GIP receptor (GIPR)-GLP-1 receptor (GLP-1R) multi-agonists exemplified by tirzepatide and emerging GIPR antagonist-GLP-1R agonist therapeutics such as maritide is increasing interest in the extra-pancreatic actions of incretin therapies. Both GLP-1 and GIP modulate inflammation, with GLP-1 also acting locally to alleviate gut inflammation in part through anti-inflammatory actions on GLP-1R+ intestinal intraepithelial lymphocytes.
View Article and Find Full Text PDFDiabetes Obes Metab
December 2024
Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, China.
Nat Biomed Eng
December 2024
Department of Genetics, Stanford University, Stanford, CA, USA.
The classification of type 2 diabetes and prediabetes does not consider heterogeneity in the pathophysiology of glucose dysregulation. Here we show that prediabetes is characterized by metabolic heterogeneity, and that metabolic subphenotypes can be predicted by the shape of the glucose curve measured via a continuous glucose monitor (CGM) during standardized oral glucose-tolerance tests (OGTTs) performed in at-home settings. Gold-standard metabolic tests in 32 individuals with early glucose dysregulation revealed dominant or co-dominant subphenotypes (muscle or hepatic insulin-resistance phenotypes in 34% of the individuals, and β-cell-dysfunction or impaired-incretin-action phenotypes in 40% of them).
View Article and Find Full Text PDFNutrients
November 2024
Applied Sport, Technology, Exercise and Medicine Research Centre, Faculty of Science and Engineering, Swansea University, Swansea SA1 8EN, UK.
Objectives: This article compares metabolic, pancreatic, and gut-derived hormone responses to isomaltulose ingestion, before versus during submaximal sustained exercise, in adults with type 1 diabetes (T1D) using automated insulin delivery systems.
Methods: In a randomized, cross-over trial, eight participants with T1D being treated with automated insulin pumps (five females, age: 47 ± 16 years, BMI: 27.5 ± 3.
Biochem Pharmacol
December 2024
Faculty of Health, School of Medicine, Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Waurn Ponds, Victoria 3216, Australia.
The relaxin-family peptide 3 receptor (RXFP3) and its native ligand, relaxin-3, are expressed in specific populations of brain neurons, and research on this system has focused on its role in the central nervous system. However, some studies have indicated that relaxin-3 and RXFP3 are also expressed in peripheral organs, including the gut. In this study, we characterised the identity of RXFP3-expressing cells in the gastrointestinal tract, using RXFP3-Cre/tdTomato reporter mice.
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