title: Lysosomal integral membrane protein Sidt2 plays a vital role in insulin secretion.
abstract: Abnormal insulin secretion results in impaired glucose tolerance and is one of the causal factors in the etiology of type 2 diabetes mellitus. Sidt2, a lysosomal integral membrane protein, plays a critical role in insulin secretion. Here, we further investigate its regulation in insulin secretion. We show that Sidt2(-/-) mice exhibit weight loss, decreased postnatal survival rate with aging, increased fasting glucose and impaired glucose tolerance. After loading high levels of glucose in their diet, Sidt2(-/-) mice produce notably lower insulin levels at the first-phase secretion compared with Sidt2(+/+) mice. Consistent with the in vivo study, INS-1 cells treated with Sidt2 siRNA produced less insulin when loaded with 16.7 mM of glucose. Only 2 of the 13 genes, synap1 and synap3 which encode soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, showed significantly decreased expression in Sidt2(-/-) mice. In conclusion, Sdit2 may play a vital role in the regulation of insulin secretion via two SNARE proteins synap1 and syanp3.
authors.affiliation: Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical CollegeWuhu, China; Anhui Province Key Laboratory of Biological Macro-Molecules Research, Wannan Medical CollegeWuhu, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical CollegeWuhu, China; Anhui Province Key Laboratory of Biological Macro-Molecules Research, Wannan Medical CollegeWuhu, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Endocrinology and Genetic Metabolism, Yijishan Hospital of Wannan Medical CollegeWuhu, China; Anhui Province Key Laboratory of Biological Macro-Molecules Research, Wannan Medical CollegeWuhu, China.
authors.forename: Qianyin
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: Anhui Province Key Laboratory of Biological Macro-Molecules Research, Wannan Medical CollegeWuhu, China; Department of Biochemistry and Molecular Biology, Wannan Medical CollageWuhu, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Anhui Province Key Laboratory of Biological Macro-Molecules Research, Wannan Medical CollegeWuhu, China; Department of Biochemistry and Molecular Biology, Wannan Medical CollageWuhu, China.
authors.forename: Lizhuo
authors.initials: L
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D005089:Exocytosis; D005260:Female; D020022:Genetic Predisposition to Disease; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D033704:Nucleotide Transport Proteins; D010641:Phenotype; D034622:RNA Interference; D051381:Rats; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D033704:Nucleotide Transport Proteins; D050600:SNARE Proteins; C554947:Sidt2 protein, mouse; C000611959:Sidt2 protein, rat
keywords: Lysosome membrane protein; Sidt2; diabetes; insulin; secretion