Given that acetylated GKRP may affiliate with type-2 diabetes mellitus (T2DM), understanding the mechanism of GKRP acetylation in the liver could reveal novel targets within the GK-GKRP pathway, for treating T2DM and other metabolic pathologies.
DNA mutations were previously identified in the glucokinase gene in 56% of French families affected with maturity onset diabetes of the young (MODY), an early onset autosomal dominant form of non-insulin-dependent diabetes mellitus (NIDDM).
A case-control design comprising 884 type 2 diabetic patients and 513 control subjects living in the East-Center of Tunisia was used to analyze the contribution to T2D of the following SNPs: E23K in KCNJ11/Kir6.2, K121Q in ENPP1, the -30G/A variant in the pancreatic beta-cell specific promoter of Glucokinase, rs7903146 in TCF7L2 encoding transcription factor 7-like2, and rs7923837 in HHEX encoding the homeobox, hematopoietically expressed transcription factor.
Polymorphisms in the glucokinase-associated, dual-specificity phosphatase 12 (DUSP12) gene under chromosome 1q21 linkage peak are associated with type 2 diabetes.
Together, we identified that ethanol-induced Atf3 fosters β-cell dysfunction via Gck down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes.
Glucokinase plays an important role in the regulation of insulin secretion and is therefore an attractive candidate gene for both insulin dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus.
Adult-onset, or type II diabetes mellitus (T2DM) has a complex genetic architecture, from hundreds of genes with low penetrance, common susceptibility variants (e.g., TCF7L2), to a set of more than ten genes that, when mutated, can cause a single-gene or Mendelian form of T2DM (e.g., GCK).
Mutations in the hepatocyte nuclear factor (HNF)-1alpha and glucokinase (GCK) genes are the major causes of monogenic forms of Type II (non-insulin-dependent) diabetes mellitus (Maturity-Onset Diabetes of the Young subtypes, MODY).
The ghrelin levels were higher in HNF1A-MODY and GCK-MODY than in T1DM and T2DM (p < 0.001 for all comparisons) but lower than in non-diabetic controls (1.02 ± 0.29 ng/ml, p < 0.001 for both comparisons).
Cystatin C levels were lower (p < 0.001) in the control (0.70 ± 0.13 mg/L), HNF1A (0.75 ± 0.21), and GCK (0.72 ± 0.16 mg/L) groups in comparison to those with either T1DM (0.87 ± 0.15 mg/L) or T2DM (0.9 ± 0.23 mg/L).
Characterization of Japanese families with early-onset type 2 (non-insulin dependent) diabetes mellitus and screening for mutations in the glucokinase and mitochondrial tRNA(Leu(UUR)) genes.