| Early insulin therapy prevents beta cell loss in a mouse model for permanent neonatal diabetes (Munich Ins2 (C95S)). | |
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MedLine Citation:
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PMID: 22095234 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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AIMS: Heterozygous male Munich Ins2 (C95S) mutant mice, a model for permanent neonatal diabetes mellitus, demonstrate a progressive diabetic phenotype with severe loss of functional beta cell mass. The aim of this study was to investigate the influence of early insulin treatment on glucose homeostasis and beta cell destruction in male Munich Ins2 (C95S) mutants. METHODS: One group of male Ins2 (C95S) mutants was treated with subcutaneous insulin pellets, as soon as blood glucose levels began to rise; placebo-treated mutants and wild-type mice served as controls. An additional group of mutant mice received a sodium-dependent glucose transporter 2 (SGLT2) inhibitor (AVE2268) via rodent chow. RESULTS: Insulin treatment normalised blood glucose concentrations, improved oral glucose tolerance, preserved insulin sensitivity and inhibited oxidative stress of Munich Ins2 (C95S) mutant mice. Pancreatic C-peptide content, as well as total beta cell and isolated beta cell volumes, of insulin-treated mutant mice were higher than those of placebo-treated mutants. In addition, alpha cell dysfunction and hyperplasia of non-beta cells were completely normalised in insulin-treated mutant mice. Treatment with the SGLT2 inhibitor lowered blood glucose, improved glucose tolerance and normalised insulin sensitivity as well as oxidative stress of Ins2 (C95S) mutants. The abundance of the endoplasmic reticulum (ER) stress markers binding Ig protein (BiP) and phosphorylated eukaryotic translation initiation factor 2 alpha (P-eIF2α) was significantly increased in the islets of mutants, before onset of hyperglycaemia, vs wild-type mice. CONCLUSIONS: We conclude that early insulin treatment protects Munich Ins2 (C95S) mutant mice from insulin resistance, alpha cell hyperfunction, beta cell loss and hyperplasia of non-beta cells, some well-known features of human diabetes mellitus. Therefore, insulin treatment may be considered early for human patients harbouring INS mutations. |
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Authors:
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S Kautz; L van Bürck; M Schuster; E Wolf; R Wanke; N Herbach |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-18 |
Journal Detail:
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Title: Diabetologia Volume: - ISSN: 1432-0428 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institute of Veterinary Pathology, Ludwig-Maximilians-Universität München, Veterinärstr. 13, 80539, Munich, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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