Data supporting phenotype of a transient neonatal diabetes point mutation (SUR1-R1183W) in mice

This data record contains 13 MS Excel files (.xls) underlying figures 1-2 and 5-8 in the associated article. The related study investigates the mechanism of neonatal diabetes remission and relapse (transient neonatal diabetes mellitus or TNDM) via mutations in mice of the K_ATP channel, a key controller of glucose homeostasis..<br><b>BACKGROUND: </b>The K_ATP channel plays a key role in glucose homeostasis by coupling metabolically generated changes in ATP to insulin secretion from pancreatic beta-cells. Gain-of-function mutations in either the pore-forming (Kir_6.2) or regulatory (SUR1) subunit of this channel are a common cause of transient neonatal diabetes mellitus, in which diabetes presents shortly after birth but remits within the first few years of life, only to return in later life. The reasons behind this time dependence are unclear. <br><br><b>METHODS: </b>In an attempt to understand the mechanism behind diabetes remission and relapse, we generated mice expressing the common TNDM mutation SUR1-R1183W. We employed Cre/LoxP technology for both inducible and constitutive expression of SUR1-R1183W specifically in mouse beta-cells, followed by investigation of their phenotype using glucose tolerance tests and insulin secretion from isolated islets. <br><br>This data record contains the following files:<br><b>figure1A.xls</b> and <b>figure1B.xls</b>: <b>A</b>: age at diagnosis, remission and relapse in the Exeter cohort of 92 TNDM patients with activating K_ATP channel mutations. <b>B</b>: The same variables for the 22 patients that had reached relapse stage at the time of study.<br><b>figure 2.xls</b>: electrophysiology results showing <b>A</b>: relative current I/I₀ vs intracellular MgATP concentration [MgATP] in µM: for Kir6.2/SUR1 (wild-type), Kir6.2/SUR1-R1183W, Kir6.2/SUR1-FLAG and Kir6.2/SUR1-R1183W-FLAG K_ATP channels. and <b>B</b>: combined effects of 30 µM gliclazide (SU) and 100 µM MgATP (ATP).<br><b>figure 5A.xls</b> and <b>figure 5B.xls</b>: <b>A</b>: Fed blood glucose levels (mM) for β-R1183W mice (n=11) and littermate controls (Cre-only, n=4) vs age in days. <b>B</b>: Intra-peritoneal glucose tolerance test: Blood glucose levels (mM) for control (Cre-only, n=4) and iβ-R1183W (R1183W, n=8) mice at 12 weeks of age, vs time in minutes.<br><b>figure 6A.xls </b>and <b>figure 6BC.xls</b>: <b>A</b>: Body weight (g), sex, genotype and identifier of control (n=5) and β-R1183W (n=10) mice on a standard and high fat diet (HFD). HFD started at 8 weeks of age. Weights reported 8 days from 15-Mar-17 to 02-May-17. <b>B</b>: Fed blood glucose levels (mM), sex, date of birth, ear punch identifier, cage number, and genotype,. Glucose levels reported at 4, 6, 8, 9, 10, 11, 12 weeks.<br><b>figure 7A.xls, figure 7B.xls, figure 7C.xls, figure 7D.xls: </b>Results for intraperitoneal glucose tolerance test (IPGTT), Intraperitoneal insulin tolerance test (IPITT) and body weight (left) and fasting blood glucose levels over time. <b>A, B:</b> Animal ID, Genotype, sex, weight and blood glucode levels (mM) for T0, T30, T60, T120 results. <b>C:</b> IPITT results: blood glucose levels (mM) for 20 week-old control (Cre-only) and β-R1183W female mice, after 12 weeks on HFD. <b>D:</b> Body weight (g), blood glucose levels (mM), for control (Cre-only) and β-R1183W female mice, at 7, 13 and 20 weeks.<br><b>figure 8A.xls and figure 8B.xls:</b> <b>A:</b> Insulin secretion from Cre-only control (C) and β-R1183W (RW) islets measured by batch incubation for 1 hour at 2 mM glucose (2G), 20 mM glucose (20G) or in the presence of 20mM glucose and 1 µM glibenclamide (SU), n=5 mice per genotype. <b>B:</b> R1183W and control (Cre-only) islet batch insulin content in µg/islet.<br>