Disease relevance of EHMT1

• We propose that the interaction of cAMP and Epac to trigger CICR explains, at least in part, the blood glucose-lowering properties of an insulinotropic hormone (glucagon-like peptide-1, also known as GLP-1) now under investigation for use in the treatment of type-2 diabetes mellitus [1].
• Because the insulinotropic actions of GLP-1 are glucose dependent, no evidence of hypoglycemia was observed [2].
• Systemic administration of expression vectors to animals using two diabetic rodent models, db/db mice and Zucker Diabetic Fatty (ZDF) rats, yielded elevated GLP-1 levels that lowered both the fasting and random-fed hyperglycemia present in these animals [2].
• GLP-1-treated ZDF rats showed diminished food intake and, in the first few weeks following vector administration, a diminished weight gain [2].
• None of the peptides significantly affected refractive error in eyes with unrestricted vision, although changes in anterior and posterior eye growth were observed in response to glucagon, oxyntomodulin, GLP-1, and miniglucagon [3].

Psychiatry related information on EHMT1

• The GLP-1 mechanism of action on insulin secretion is at least partly mediated via receptors on the pancreatic islet, but the mechanism by which GLP-1 retards gastric emptying is not known and may involve neural interactions, although GLP-1 has no effect on vagally stimulated motor activity of the isolated porcine antrum [4].

High impact information on EHMT1

• Plasma GLP-1, insulin, glucagon, and blood glucose profiles were affected significantly by the treatment (P < 0.002) [5].
• Most importantly, we identified two de novo mutations--a nonsense mutation and a frameshift mutation--in the EHMT1 gene in patients with a typical 9q- phenotype [6].
• The minimal critical region responsible for this 9q subtelomeric deletion (9q-) syndrome has been estimated to be <1 Mb and comprises the euchromatin histone methyl transferase 1 gene (EHMT1) [6].
• GLP-1 also inhibits glucagon secretion and inhibits gastric emptying and gastric acid and pancreatic exocrine secretion [7].
• BACKGROUND: The glucagon-like peptides (GLP) 1 and 2 are secreted postprandially from L cells located mainly in the ileum [8].

Chemical compound and disease context of EHMT1

• Five Weeks of Treatment with the GLP-1 Analogue Liraglutide Improves Glycaemic Control and Lowers Body weight in Subjects with Type 2 Diabetes [9].

Biological context of EHMT1

• However, a trend was observed: homozygotes for the rare alleles of the EHMT1, EHMT2 and PRDM2 had a mean value for both trimethylation of K9 and K27 of histone H3 remarkably different to the homozygotes for the common alleles [10].
• Elevated GLP-1 and GLP-2 concentrations may contribute to the positive effects of a preserved colon on intestinal motility and functional adaptation in ileum resected short bowel patients [8].
• In the short term, there appears to be no tachyphylaxis, since insulin stimulation and glucagon suppression were similar upon repeated administrations of GLP-1 [7-36 amide] [11].
• This plasmid allows for expression of bivalent GLP-1 peptide ligands as a result of IgG-Fc homodimerization [12].
• Glucagon-like peptide (GLP-1), a major physiological incretin, plays numerous important roles in modulating blood glucose homeostasis and has been proposed for the treatment of type 2 diabetes [12].

Anatomical context of EHMT1

• In females, loss of GLP-1 leads to a severe block in germ cell development as early as E17 [13].
• Here we report the identification and characterization of a novel nuclear zinc finger protein called GATA like protein-1 (GLP-1), which is expressed at high levels in the somatic cells of the developing gonads, including Leydig cells in the testes and granulosa cells in the ovaries [13].
• Loss of GLP-1 leads to defective sperm development in males with a marked reduction in mature spermatids observed as early as postnatal week 1 [13].
• Glucagon and glucagon-like peptide (GLP) were isolated from an extract of bowfin pancreas and their primary structures determined [14].
• Bowfin GLP stimulated glycogenolysis in rockfish hepatocytes, but was 3-fold less effective and 23-fold less potent than human GLP-1-(7-37)-peptide [14].

Associations of EHMT1 with chemical compounds

• Insulin levels were similar between the three regimens, but glucagon levels were significantly reduced with GLP-1 compared with metformin (P = 0.0003) [15].
• In IGT, insulin levels were significantly lower during the first phase (144 +/- 20 vs. 397 +/- 119 pmol/L; P = 0.02), at the end of the GLP infusion (2142 +/- 350 vs. 5430 +/- 1091 pmol/L; P: = 0.002), and in response to arginine (3983 +/- 375 vs. 8663 +/- 1430 pmol/L; P = 0.005) [16].
• The major obstacles for using native GLP-1 as a therapeutic agent are that it must be delivered by a parenteral route and has a short half-life [12].
• The effect of GLP-1 on glucose appearance (Ra) and glucose disposal (Rd) was measured in eight men during a pancreatic clamp that was performed by infusing octreotide to suppress secretion of islet hormones, while insulin and glucagon were infused at rates adjusted to maintain blood glucose near fasting levels [17].
• Analysis of the nucleotide sequence and deduced amino acid sequence revealed a high homology with germin-like proteins (GLPs), and particularly with an auxin-binding protein from peach, ABP19, that belongs to the GLP family [18].

Other interactions of EHMT1

• GLP-1 controls blood glucose through regulation of glucose-dependent insulin secretion, inhibition of glucagon secretion and gastric emptying, and reduction of food intake [19].
• Administration of GLP-1 is highly effective in reducing blood glucose in subjects with type 2 diabetes but native GLP-1 is rapidly degraded by dipeptidyl peptidase IV [19].

Analytical, diagnostic and therapeutic context of EHMT1

• METHODS: GLP-1 and GLP-2 immunoreactivity was measured by specific radioimmunoassays in plasma collected at fasting and at regular intervals 180 minutes after a test meal [8].
• These results demonstrate the feasibility of gene therapy for type II diabetes using GLP-1 expression vectors.Gene Therapy (2007) 14, 38-48. doi:10.1038/sj.gt.3302842; published online 24 August 2006 [2].
• Use of macroaggregated serum albumin particles as surrogates for initial short-term biodistribution and safety analysis will advance hepatocyte transplantation, as the cost of GLP-certified laboratories and consumption of scarce donor livers will be avoided [20].
• Plasma glucose, immunoreactive insulin (IRI), C-peptide, glucagon, and GLP-1 levels at each time point during OGTT were measured [21].
• Blood was drawn in 30-min intervals for glucose (glucose oxidase), insulin, C-peptide, glucagon, and GLP-1 (specific immunoassays) [22].

References