Mutations in
glucokinase, HNF-1[alpha], HNF-1[beta], HNF-4[alpha], IPF-1, and Neuro-D1 genes linked with early onset autosomal type 2 diabetes were searched for by means of a double gradient, denaturing gradient gel electrophoresis.
GKM 001, a
glucokinase modulator, will have a clear edge over existing approaches to type 2 diabetes, believes Dr.
Among monogenic forms of T2DM, the most common is the maturity onset diabetes of the young (MODY), a genetically heterogeneous disease caused by mutations in the genes encoding hepatocyte nuclear factor-4a (MODY 1),
glucokinase (MODY 2), hepatocyte nuclear factor 1a (MODY 3), insulin promoter factor-1 (MODY 4), hepatocyte nuclear factor-1b (MODY 5) and neuro D (MODY 6).
The cytosolic glucose concentration in hepatocytes higher than most other cell types is due to the presence of a higher [K.sub.m] glucose transporter (GLUT2), a higher Km hexokinase (
glucokinase), different insulin sensitivity, and different metabolic activity [101, page 59], [102, 103].
Imachi et al., "Exendin-4 regulates
glucokinase expression by CaMKK/CaMKIV pathway in pancreatic [beta]-cell line," Diabetes, Obesity and Metabolism, vol.
"Biotin regulation of pancreatic
glucokinase and insulin in primary cultured rat islets and in biotindeficient rats." Endocrinology, 1999; 140(10):4595-600.
Our patient with hyperglycemia and dysmorphic features had a deletion of 7.23 Mb comprising the region 7p13-p12.1, with involvement of 39 Online Mendelian Inheritance in Man genes, including
glucokinase associated with maturity-onset diabetes of the young, CCM2 associated with type 2 cerebral cavernous malformations, insulin-like growth factors binding protein-3 associated with decreased postnatal growth, and oxoglutarate dehydrogenase associated with alpha-ketoglutarate dehydrogenase deficiency (short stature, hypotonia, cognitive impairment, and movement abnormalities).
The supernatant was separated and divided into three parts for measurement of
glucokinase (GK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) activity.
Further, the molecular interaction study of the ligands 1, 2 and glibenclamide with various diabetes mellitus related protein targets like
glucokinase (PDB ID: 1V4S), fructose-1,6-bisphosphatase 1 (PDB ID: 2JJK) 11-[beta]-hydroxysteroid dehydrogenase (PDB ID: 2BEL) and modeled protein sulfonylurea receptor 1 (SUR1) showed that ligand 1 and 2 possess binding affinity with all protein targets except for 2BEL target protein for which ligand 1 has no interaction.