Similar Datasets
Project description:RNAseq of pancreatic islets of db/db mice treated with AAV- Adipsin vs AAV-GFP 4 weeks post AAV injection
2020-02-04 | GSE144575 | GEO
Project description:Diabetes is a complex genetic disease affecting millions of people worldwide. A common monogenic form of diabetes is glucokinase (GCK) maturity-onset diabetes of the young (GCK-MODY), which is caused by heterozygous inactivating variants in the gene encoding GCK. GCK catalyzes the phosphorylation of glucose and is known as the pancreatic glucose sensor. Patients with GCK-MODY, in contrast to other diabetics, often do not require treatment but are frequently misdiagnosed and treated unnecessarily. Genetic testing can prevent this, but is hampered by the challenge of interpreting genetic variants. To address this challenge, we generated a comprehensive map of human GCK variant activity. The activity map includes 97% of the possible missense and nonsense variants and correlate with in vitro catalytic efficiency, fasting glucose levels in patients and evolutionary conservation analysis. Activity scores include both hyper- and hypoactive variants.
2022-06-16 | GSE198878 | GEO
Project description:Amino acid substitutions can perturb protein activity in multiple ways. Understanding their mechanistic basis may pinpoint how residues contribute to protein function. Here, we characterize the mechanisms of human glucokinase (GCK) variants, building on our previous comprehensive study on GCK variant activity. We assayed the abundance of 95\% GCK missense and nonsense variants, and found that 59\% of hypoactive variants have a decreased cellular abundance. By combining our abundance scores with predictions of protein thermodynamic stability, we identify residues important for GCK metabolic stability and conformational dynamics. These residues could be targeted to modulate GCK activity, and thereby affect glucose homeostasis.
2023-05-22 | GSE226732 | GEO
Project description:Beta cell-targeted glucokinase overexpression
| PRJNA413133 | ENA
Project description:Analysis of genes from glucokinase-expressing cells following immunoprecipitation of hypothalamic EGFP-tagged L10 ribosomal protein from Glucokinase-cre/Elongation factor 1 alpha 1 - lox stop lox - EGFPL10 mice mRNA obtained by immunoprecipitation in adult Gck-cre/EF1A1-LSL-EGFPL10 mice
2013-09-13 | E-GEOD-49868 | biostudies-arrayexpress
Project description:We compared RNA expression profiles of wild type of mice maintained on high fat diet or Irs1/2:foxo1-LTKO mice infected with Fst288 AAV-TBG virus Fst288-AAV-TBG infection modestly up- or down-regulated the expression of many genes, including several related to hepatic glucose metabolism (Pck1, G6pc and Gck) (Fig. S8a); qPCR confirmed that Fst288AAV•TBG affected the expression of these and other genes during both fasting (Pck1, G6pc and Gck) and feeding (Foxo1, Igfbp1, Pck1, and Ppargc1a)
2018-03-14 | GSE111745 | GEO
Project description:To model the potential diabetogenic effects of higher level of HSD11B1 in b-cells of the pancreas in vivo, we created a transgenic model overexpressing HSD11B1 under the mouse insulin I promoter (MIP-HSD1) in diabetes-prone C57Bl/KsJ mice. KsJ wild type and MIP-HSD1 heterozygous mice have been high fat fed for 12 weeks. Pancreata have been perfused with collagenase and islets isolated by hand picking. Isolated islets (around 500) coming from at least 3 mice (around 200/mice) have been directly lysed in Trizol. Total RNA have been extracted by Trizol plus RNA Purification Kit (invitrogen). Four biological replicates per group: Wild type KsJ mice on High Fat diet (KsJ1, KsJ2, KsJ3, KsJ4) and MIP-HSD1 transgenic mice on High Fat diet (MIP1, MIP2, MIP3, MIP4) were used to prepare RNA for microarray analysis.
2011-06-30 | E-GEOD-23161 | biostudies-arrayexpress
Project description:Diabetes is a disorder characterized by loss of beta cell mass and/or beta cell function, leading to deficiency of insulin relative to metabolic need. To determine whether stem cell derived-beta cells faithfully reflect the phenotypes of a diabetic subject, we generated induced pluripotent stem cells from diabetic subjects (MODY2) with heterozygous loss-of-function of the gene encoding glucokinase (GCK). These stem cells differentiated into beta cells with an efficiency comparable to controls, and expressed markers of mature beta cells, urocotin-3 and zinc transporter 8 upon transplantation into mice. While insulin secretion in response to arginine or other secretagogues was identical to cells from healthy controls, GCK mutant beta cells required higher glucose levels to stimulate insulin secretion. Importantly this glucose-specific phenotype was fully reverted upon gene sequence correction by homologous recombination. Our results demonstrate that stem cell-derived beta cells reflect beta cell-autonomous phenotypes of MODY2 subjects, providing a platform for mechanistic analysis of specific genotypes on beta cell function. Induced pluripotent stem cells with munations in the glucokinase gene were differentiationed into pancreas cells using published protocol (D'Amour et al, 2006) with certain modifications. 1 million cells(fibroblast or stem cells or differentiated pancreatic cells) was used for RNA extraction and labeling using the Illumina total prep RNA amplification kit.
2013-04-05 | E-GEOD-45777 | biostudies-arrayexpress
Project description:Diabetes is a disorder characterized by loss of beta cell mass and/or beta cell function, leading to deficiency of insulin relative to metabolic need. To determine whether stem cell derived-beta cells faithfully reflect the phenotypes of a diabetic subject, we generated induced pluripotent stem cells from diabetic subjects (MODY2) with heterozygous loss-of-function of the gene encoding glucokinase (GCK). These stem cells differentiated into beta cells with an efficiency comparable to controls, and expressed markers of mature beta cells, urocotin-3 and zinc transporter 8 upon transplantation into mice. While insulin secretion in response to arginine or other secretagogues was identical to cells from healthy controls, GCK mutant beta cells required higher glucose levels to stimulate insulin secretion. Importantly this glucose-specific phenotype was fully reverted upon gene sequence correction by homologous recombination. Our results demonstrate that stem cell-derived beta cells reflect beta cell-autonomous phenotypes of MODY2 subjects, providing a platform for mechanistic analysis of specific genotypes on beta cell function.
2013-04-05 | GSE45777 | GEO
Project description:Context: We present a case of a young adult with GCK mutation who had neonatal hypoglycaemia, re-emerging with hypoglycaemia later in life. Mechanistic insight is gained from detailed clinical, cellular and genomic analysis. Conclusion: This case highlights the variable phenotype of GCK mutations. In depth molecular analyses in the islets has revealed possible mechanisms for nesidioblastosis and insulin hypersecretion.
2022-03-12 | GSE193693 | GEO