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Here, we uncover a conserved program of alternative microexons included in mRNAs of islet cells, particularly in genes involved in vesicle transport and exocytosis. Islet microexons (IsletMICs) are regulated by the RNA binding protein SRRM3 and represent a subset of the larger neural program that are particularly sensitive to the levels of this protein. Both SRRM3 and IsletMICs are induced by elevated glucose levels, and depletion of SRRM3 in beta cell lines and mouse islets, or repression of particular IsletMICs using antisense oligonucleotides, leads to inappropriate insulin secretion. Consistently, SRRM3 mutant mice display defects in islet cell identity and function, leading to hyperinsulinemic hypoglycemia. Importantly, human genetic variants that influence SRRM3 expression and microexon inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk. Overall design: Srrm3 was depleted or overexpressed in different systems to investigate regulation of microexons."],"repository":["ENA"],"description_synonyms":["Type 2 diabetes, T2DM - Type 2 Diabetes mellitus, Adult-Onset Diabetes Mellitus, Diabetes Type 2, type 2, Controlling, preventive therapy, Adult-onset diabetes, Type 2 diabetes mellitus, Noninsulin Dependent, Adult-onset diabetes mellitus, islet of Langerhans, MODY, Type 2 Diabetes Mellitus, function, DIABETES MELLITUS TYPE 02, Islets, Nesidioblasts, diabetes mellitus type 2, Cell, Maturity-onset diabetes, prevention, islets of Langerhans, Noninsulin-dependent diabetes mellitus, Pancreatic Islet, Programs, Adult-Onset, pancreatic islet, T2D, Adult-Onset Diabetes, Islet, Non-Insulin-Dependent, island of pancreas, Slow-Onset Diabetes Mellitus, Maturity-Onset, Non-Insulin Dependent Diabetes Mellitus, Maturity Onset Diabetes, Langerhans Islands, Type 2 Diabetes Mellitus Non-Insulin Dependent, non-insulin-dependent diabetes mellitus, Ketosis Resistant, Pancreatic, Islands of Langerhans, prevention and control, Slow Onset, Maturity-Onset Diabetes Mellitus, Maturity-Onset Diabetes, T2DM, Endocrine Pancreas, Type 2 Diabetes, reference sample, Endocrine, prophylaxis, Non-Insulin-Dependent Diabetes Mellitus, Type II Diabetes, Nesidioblast, Islet Cells, Pancreatic Islets, Maturity Onset Diabetes Mellitus, Type 2, adult-onset, island of Langerhans, Stable Diabetes Mellitus., Pancreas, Ketosis-Resistant Diabetes Mellitus, NIDDM, preventive measures, Noninsulin-Dependent Diabetes Mellitus, type II, Noninsulin-Dependent, Langerhans Islets, Diabetes mellitus, non-insulin-dependent, Non-Insulin Dependent Diabetes, Maturity-onset diabetes mellitus, Noninsulin Dependent Diabetes Mellitus, Islet Cell, pancreatic insula, Stable, control, MODY (Maturity-onset diabetes of the young), Diabetes Mellitus, Cells, Ketosis-Resistant, Type II, Non Insulin Dependent, Slow-Onset, Diabetes, Maturity Onset, Controlled, Adult Onset"],"name_synonyms":["Type 2 diabetes, T2DM - Type 2 Diabetes mellitus, Adult-Onset Diabetes Mellitus, Diabetes Type 2, type 2, Controlling, preventive therapy, Adult-onset diabetes, Type 2 diabetes mellitus, Noninsulin Dependent, Adult-onset diabetes mellitus, islet of Langerhans, MODY, Type 2 Diabetes Mellitus, function, DIABETES MELLITUS TYPE 02, Islets, Nesidioblasts, diabetes mellitus type 2, Cell, Maturity-onset diabetes, prevention, islets of Langerhans, Noninsulin-dependent diabetes mellitus, Pancreatic Islet, Programs, Adult-Onset, pancreatic islet, T2D, Adult-Onset Diabetes, Islet, Non-Insulin-Dependent, island of pancreas, Slow-Onset Diabetes Mellitus, Maturity-Onset, Non-Insulin Dependent Diabetes Mellitus, Maturity Onset Diabetes, Langerhans Islands, Type 2 Diabetes Mellitus Non-Insulin Dependent, non-insulin-dependent diabetes mellitus, Ketosis Resistant, Pancreatic, Islands of Langerhans, prevention and control, Slow Onset, Maturity-Onset Diabetes Mellitus, Maturity-Onset Diabetes, T2DM, Endocrine Pancreas, Type 2 Diabetes, reference sample, Endocrine, prophylaxis, Non-Insulin-Dependent Diabetes Mellitus, Type II Diabetes, Nesidioblast, Islet Cells, Pancreatic Islets, Maturity Onset Diabetes Mellitus, Type 2, adult-onset, island of Langerhans, Stable Diabetes Mellitus., Pancreas, Ketosis-Resistant Diabetes Mellitus, NIDDM, preventive measures, Noninsulin-Dependent Diabetes Mellitus, type II, Noninsulin-Dependent, Langerhans Islets, Diabetes mellitus, non-insulin-dependent, Non-Insulin Dependent Diabetes, Maturity-onset diabetes mellitus, Noninsulin Dependent Diabetes Mellitus, Islet Cell, pancreatic insula, Stable, control, MODY (Maturity-onset diabetes of the young), Diabetes Mellitus, Cells, Ketosis-Resistant, Type II, Non Insulin Dependent, Slow-Onset, Diabetes, Maturity Onset, Controlled, Adult Onset"],"additional_accession":[]},"is_claimable":false,"name":"Control of pancreatic islet function and glucose homeostasis by a novel microexon program misregulated in type 2 diabetes","description":"Control of pancreatic islet function and glucose homeostasis by a novel microexon program misregulated in type 2 diabetes","dates":{"last_updated":"2023-05-19","first_public":"2022-12-24"},"accession":"PRJNA817274","cross_references":{"GEO":["GSE198906"],"PubMed":["36759540"]}}