SNAP25 is a core protein of the SNARE complex, which mediates stimulus-dependent secretion of insulin from the pancreatic β cells. SNAP23 is a SNAP25 homolog, however, the functional role of SNAP23 in the exocytic secretion of insulin is not known. Therefore, in the present study, we investigated the functional role of SNAP23 in the insulin secretory pathway. Our results demonstrated that over-expression of SNAP23 inhibited the secretion of insulin from the INS-1 cells. Conversely, SNAP23 depletion increased insulin secretion. Mechanistically, overexpression of SNAP23 decreased SNARE complex formation by blocking the binding of SNAP25 to STX1A. The full-length SNAP23 protein with the N-terminal and C-terminal SNARE binding domains was required for competition. Moreover, SNAP23 serine 95 phosphorylation plays a crucial function in insulin secretion by enhancing the interaction between SNAP23 and STX1A. The present study presents a new pathway regulating insulin secretion. Therefore, SNAP23 may be a potential therapeutic target for diabetes mellitus.
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http://dx.doi.org/10.1042/BSR20222594 | DOI Listing |
Diabetes Metab Syndr Obes
January 2025
Department of Diabetes, Metabolism and Endocrinology, Toho University Graduate School of Medicine, Tokyo, Japan.
Purpose: Imeglimin is a novel oral antidiabetic agent that improves glucose tolerance. This study aimed to investigate the efficacy of combining imeglimin with dipeptidyl peptidase-4 inhibitor (DPP-4i), the most frequently prescribed first-line treatment for patients with type 2 diabetes (T2D) in Japan, to improve glycemic control.
Patients And Methods: Eleven patients with T2D treated with DPP-4i alone (6.
Diabetes Obes Metab
January 2025
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Aims: To compare the probability of achieving diabetes remission in individuals with different phenotypes of insulin sensitivity, insulin secretion, and beta cell function and further detect the effects of diet, exercise, and lifestyle education intervention on these indexes.
Methods: Three-hundred and one participants who had glycated haemoglobin (HbA1c) data at baseline and after intervention were included for this post hoc analysis. We used the multi-way analysis of variance to assess the differences between the diabetes remission and non-remission groups or between intervention groups in changes of the indexes of insulin sensitivity, insulin secretion, and beta cell function.
Diabetes Obes Metab
January 2025
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Aim: To achieve glucose-activated transcriptional regulation of insulin analogue in skeletal muscle of T1D mice, thereby controlling blood glucose levels and preventing or mitigating diabetes-related complications.
Materials And Methods: We developed the GANIT (Glucose-Activated NFAT-regulated INSA-F Transcription) system, an innovative platform building upon the previously established intramuscular plasmid DNA (pDNA) delivery and expression system. In the GANIT system, skeletal muscle cells are genetically engineered to endogenously produce the insulin analogue INSA-F (Insulin Aspart with Furin cleavage sites).
J Atheroscler Thromb
January 2025
Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a pervasive chronic disease that affects millions of people worldwide. It predisposes individuals to a range of severe microvascular and macrovascular complications, which drastically impact the patient's quality of life and increase mortality rates owing to various comorbidities. This extensive review explores the intricate pathophysiology underlying diabetic complications, focusing on key mechanisms, such as atherosclerosis, insulin resistance, chronic inflammation, and endothelial dysfunction.
View Article and Find Full Text PDFDiabetes Care
January 2025
Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Objective: In the Diabetes Virus Detection and Intervention trial, antiviral treatment with pleconaril and ribavirin decreased the decline, compared with placebo, in endogenous C-peptide 1 year after diagnosis of type 1 diabetes (T1D) in children and adolescents. This article reports the results 2 and 3 years after diagnosis.
Research Design And Methods: This was a multicenter, randomized, placebo-controlled (1:1) trial of 96 children and adolescents aged 6-15.
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