Heterozygous mutations of TCF2 (transcription factor 2) have been associated with maturity onset diabetes of the young, renal malformations, hyperuricemia, and occasionally internal genital malformations in female. We report a female patient with bilateral renal hypodysplasia and de novo heterozygous TCF2 gene mutation. At the age of 9 yr, she ...

Two of the three [NiFe]-hydrogenases (Hyd) of Escherichia coli have a hydrogen-uptake function in anaerobic metabolism. While Hyd-2 is maximally synthesized when the bacterium grows by fumarate respiration, Hyd-1 synthesis shows a correlation with fermentation of sugar substrates. In an attempt to advance our knowledge on the physiological function of ...

A letter in response to: Sato R, Watanabe H, Genma R et al. ABCC8 polymorphism (Ser1369Ala): influence on severe hypoglycemia due to sulfonylureas. Pharmacogenomics 11(12), 1743-1750 (2010).

It has recently been suggested that the low-frequency c.136-14_136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in ...

OBJECTIVEGain-of-function ABCC8/sulfonylurea (SU) receptor 1 mutations cause neonatal diabetes mellitus (NDM) or late-onset diabetes in adult relatives. Given the effectiveness of SU treatment in ABCC8-NDM patients, we further characterized late-onset ABCC8-associated diabetes.RESEARCH DESIGN AND METHODSSeven adult subjects from three NDM families and one family with type 2 diabetes were studied. ...

The function of two fission yeast genes, SPCC74.03c/ssp2(+) and SPAC23H4.02/ppk9(+), encoding a Snf1-like protein kinase were investigated. Deletion of ssp2(+) caused a partial defect in glucose derepression of inv1(+), fbp1(+) and gld1(+), and in assimilation of sucrose and glycerol, while a mutation in ppk9(+) had no apparent effect. Scr1, a ...

We investigated the association of CDKAL1 (rs7754840 and rs7756992) and CDKN2A/2B (rs10811661) variants with T2DM. Higher MAF of rs7754840 and rs7756992 were seen in patients, and both were associated with T2DM under additive, dominant, and recessive models. CDKAL1 rs7754840 and rs7756992, but not CDKN2A/2B rs10811661, are associated with T2DM in ...

AIMS: Heterozygous male Munich Ins2 (C95S) mutant mice, a model for permanent neonatal diabetes mellitus, demonstrate a progressive diabetic phenotype with severe loss of functional beta cell mass. The aim of this study was to investigate the influence of early insulin treatment on glucose homeostasis and beta cell destruction in ...

PAS kinase (PASK) is a glucose-regulated protein kinase involved in the control of pancreatic islet hormone release and insulin sensitivity. We aimed here to identify mutations in the PASK gene which may be associated with young-onset diabetes in humans. We screened 18 diabetic probands with unelucidated Maturity-Onset Diabetes of the ...

Shewanella oneidensis MR-1 has conventionally been considered unable to use glucose as a carbon substrate for growth. The genome sequence of S. oneidensis MR-1 however, suggests the ability to use glucose. Here we demonstrate that during initial glucose exposure, S. oneidensis MR-1 quickly and frequently gains the ability to utilize ...

Objective: Glucocorticoid receptor (GR) polymorphisms alter glucocorticoid sensitivity and have been associated with altered metabolic profiles. We evaluate the prevalence of the four GR polymorphisms BclI, N363S, ER22/23EK and A3669G in patients with Cushing's Syndrome (CS) compared to healthy controls (HC) and we investigate their role in the development of ...

Aims:  The application of Ralstonia eutropha H16 for producing polyhydroxyalkanoates as bioplastics is limited by the incapability of the bacterium to utilize glucose as a growth substrate. This study aims in characterizing glucose-utilizing strains which arose after incubation with high glucose levels, in comparison to previously published mutants, generated either ...

Mutations in the insulin gene can impair proinsulin folding and cause diabetes mellitus. Although crystal structures of insulin dimers and hexamers are well established, proinsulin is refractory to crystallization. Whereas an NMR structure of an engineered proinsulin monomer has been reported, structures of the wild-type monomer and hexamer remain undetermined. ...

There has been major progress in recent years uncovering the genetic causes of diabetes presenting in the first year of life. Twenty genes have been identified to date. The most common causes accounting for the majority of cases are mutations in the genes encoding the two subunits of the ATP-sensitive ...

Recent studies have identified common variants in forkhead box O3 gene (FOXO3) to be strongly associated with longevity in different populations. But studies have not been carried out to analyse the role of common variants in FOXO3 with type 2 diabetes. Since type 2 diabetes is an age related disorder ...

Pathological fasting hypoglycemia in humans is usually explained by excessive circulating insulin or insulin-like molecules or by inborn errors of metabolism impairing liver glucose production. We studied three unrelated children with unexplained, recurrent, and severe fasting hypoglycemia and asymmetrical growth. All were found to carry the same de novo mutation, ...

Laboratory adaptive evolution of microorganisms offers the possibility of relating acquired mutations to increased fitness of the organism under the conditions used. By combining a fibrous-bed bioreactor, we successfully developed a simple and valuable adaptive evolution strategy in repeated-batch fermentation mode with high initial substrate concentration and evolved Clostridium tyrobutyricum ...

In Caenorhabditis elegans, the insulin/IGF pathway participates in the decision to initiate dauer development. Dauer is a diapause stage that is triggered by environmental stresses, such as a lack of nutrients. Insulin/IGF receptor mutants arrest constitutively in dauer, an effect that can be suppressed by mutations in other elements of ...

We performed genome-wide mutagenesis in C57BL/6J mice using N-ethyl-N-nitrosourea (ENU) to identify mutations causing high blood glucose early in life, and to produce new animal models of diabetes. Of a total of 13 new lines confirmed by heritability testing, we identified two semi-dominant pedigrees with novel missense mutations in the ...

Diabetes mellitus classified as Maturity Onset Diabetes of the Young (MODY) is characterized by autosomal dominant inheritance with insulin secretory disturbances.In 2 siblings with diabetes mellitus manifestation at age under 25 years, low fasting glucose levels, severely elevated glucose levels upon glucose challenge and absent autoantibodies for IA2 and GAD ...

Aims:  Recently, an association between two polymorphisms (1181G>C and 245T>G) of the osteoprotegerin (OPG) gene and diabetic Charcot neuroarthropathy was suggested on the basis of studies of a limited number of samples derived from subjects from one geographical region (Italy). The aim of this study was to assess the presence ...

Rachmiel M, Rubio-Cabezas O, Ellard S, Hattersley AT, Perlman K. Early-onset, severe lipoatrophy in a patient with permanent neonatal diabetes mellitus secondary to a recessive mutation in the INS gene. We describe a case of neonatal diabetes due to a homozygous mutation (c.3 G>T) at the INS gene, leading to ...

Purpose:To investigate whether variants in cardiovascular candidate genes, some of which have been previously associated with type 2 diabetes (T2D), diabetic retinopathy (DR), and diabetic nephropathy (DN), are associated with DR in the Candidate-gene Association Resource (CARe).Methods:2691 persons with T2D had fundus photography and genotyping of single nucleotide polymorphisms (SNPs) ...

KCNJ11 gene mutations are related to permanent neonatal diabetes mellitus (PNDM). Glycemic stability minimizes the risk of complications. Sulfonylureas (SU) are the proven best therapeutic option. We report a 18-month follow-up of switching from insulin to SU in a mother and her daughter with PNDM due to KCNJ11 mutation.

AIMS/HYPOTHESIS: The glucagon gene (GCG) encodes several hormones important for energy metabolism: glucagon, oxyntomodulin and glucagon-like peptide (GLP)-1 and -2. Variants in GCG may associate with type 2 diabetes, obesity and/or related metabolic traits. METHODS: GCG was re-sequenced as a candidate gene in 865 European individuals. Twenty-nine variants were identified. ...

Common variants of fat mass and obesity-associated gene (FTO, fat mass- and obesity-associated gene) have been shown to be associated with obesity and type 2 diabetes in population of European and non-European ethnicity. However, studies in Indian population have provided inconsistent results. Here, we examined association of eight FTO variants ...

Variants in genes involved in pancreatic β-cell development and function are known to cause monogenic forms of type 2 diabetes and are also associated with complex form. In this study, we studied the genetic association of polymorphisms in such important genes with type 2 diabetes in the high-risk Indians. We ...

The goal of this review is to provide an update on the different forms of monogenic diabetes, including maturity-onset diabetes of the young (MODY) and neonatal diabetes (permanent and transient neonatal diabetes). Monogenic diabetes accounts for approximately 1-2% of diabetes cases and results from mutations that primarily reduce β-cell function. ...

Background: Mutations in the insulin-like growth factor-I (IGF-I) receptor (IGF1R) have been associated with prenatal and postnatal growth retardation. However, little is known about potential effects of mutations in the IGF1R on carbohydrate homeostasis. Methods: We investigated clinical, endocrine and metabolic parameters in four family members carrying a novel IGF1R ...

Gonc EN, Ozturk BB, Haldorsen IS, Molnes J, Immervoll H, Raeder H, Molven A, Søvik O, Njølstad PR. HNF1B mutation in a Turkish child with renal and exocrine pancreas insufficiency, diabetes and liver disease. A small-for-gestational age female infant presented with bilateral hypoplastic kidneys at 3 months of age. She ...

The facilitative glucose transporter GLUT4 plays a key role in regulating whole-body glucose homeostasis. GLUT4 dramatically changes its distribution upon insulin stimulation, and insulin-resistant diabetes is often linked with compromised translocation of GLUT4 under insulin stimulation. To elucidate the functional significance of the sole N-glycan chain on GLUT4, wild-type GLUT4 ...

Background: Diabetic retinopathy is a long-term complication of type 2 diabetes (T2D). Non-diabetic retinopathy may be present in T2D patients as well and non-T2D patients with hypertension and/or atherosclerosis. The aim of this study was to identify linkage of the proteasome modulator 9 (PSMD9) T2D risk variants IVS3+nt460, IVS3+nt437, E197G ...

Objective:  Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by parathyroid, gastroenteropancreatic, pituitary and adrenal tumours. Cardiovascular disease has been identified as an important cause of death in MEN1 patients. Menin, the product of the MEN1 gene, is a co-activator for peroxisome proliferator-activated receptor-γ and the vitamin ...

Insulin is a hormone that regulates the physiological glucose level in human blood. Insulin injections are used to treat diabetic patients. The amyloid aggregation of insulin may cause problems during the production, storage, and delivery of insulin formulations. Several modifications to the C-terminus of the B chain have been suggested ...

AIMS/HYPOTHESIS: Dominantly acting loss-of-function mutations in the ABCC8/KCNJ11 genes can cause mild medically responsive hyperinsulinaemic hypoglycaemia (HH). As controversy exists over whether these mutations predispose to diabetes in adulthood we investigated the prevalence of diabetes in families with dominantly inherited ATP-sensitive potassium (K(ATP)) channel mutations causing HH in the proband. ...

Neonatal diabetes mellitus (NDM) is a rare disorder. A one-month-old boy presented with vomiting, hyperglycemia (968 mg/dl [53.8 mmol/L]), severe acetonemia, and metabolic acidosis (pH 6.95, HCO3-4.2 mmol/L). A second child (three months of age) presented with upper respiratory tract symptoms and a plasma glucose level of 835 mg/dl, without ...

Single nucleotide polymorphisms (SNPs) in MYH9 and APOL1 on chromosome 22 (c22) are powerfully associated with non-diabetic end-stage renal disease (ESRD) in African Americans (AAs). Many AAs diagnosed with type 2 diabetic nephropathy (T2DN) have non-diabetic kidney disease, potentially masking detection of DN genes. Therefore, genome-wide association analyses were performed ...

Diabet. Med. 28, 681-684 (2011) ABSTRACT: Aim  Genome-wide association studies have identified > 30 common variants associated with Type 2 diabetes (> 5% minor allele frequency). These variants have small effects on individual risk and do not account for a large proportion of the heritable component of the disease. Monogenic forms of diabetes ...

OBJECTIVE Two novel mutations (E1506D, E1506G) in the nucleotide-binding domain 2 (NBD2) of the ATP-sensitive K(+) channel (K(ATP) channel) sulfonylurea receptor 1 (SUR1) subunit were detected heterozygously in patients with neonatal diabetes. A mutation at the same residue (E1506K) was previously shown to cause congenital hyperinsulinemia. We sought to understand ...

OBJECTIVE: Several factors either predisposing or protecting from the onset of diabetes mellitus type 2 (DM2) have been proposed. Two specific polymorphisms of Toll-like receptor-4 (Asp299Gly and Thr399Ile) have been recently identified either as candidate protector genes against DM2 and associated neuropathy or risk alleles for the manifestation of diabetic ...

Purpose. Wolfram syndrome (WS) or diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD) (OMIM 222300) is an inherited neurodegenerative disease characterized by diabetes mellitus and optic atrophy as the 2 major criteria, followed later in life by deafness, diabetes insipidus, and various signs of neurologic impairment. The presence of ...

Kruppel like transcription factors (KLFs) have elicited significant attention due to their regulation of essential biochemical pathways and, more recently, due to their fundamental role in the mechanisms of human diseases. Neonatal Diabetes Mellitus (NDM) is a monogenic disorder with primary alterations in insulin secretion. We here describe a key ...

Listeria monocytogenes transports glucose/mannose via non-PTS permeases and phosphoenolpyruvate:carbohydrate phosphotransferase systems (PTS). Two mannose class PTS are encoded by the constitutively expressed mpoABCD and the inducible manLMN operons. The man operon encodes the main glucose transporter because manL or manM deletion significantly slows glucose utilization, whereas mpoA deletion has no ...

Background: Mutations of the preproinsulin gene (INS) account for both permanent neonatal diabetes (PND) and adult-onset diabetes. The molecular mechanism of complete INS-deletion has recently been published and we now add clinical data of homozygous and heterozygous subjects as well as the detailed mapping of the 646 bp deletion of ...

Objective:  Wolfram syndrome is a rare form of diabetes mellitus associated with optic atrophy and disorders of different organs (e.g., diabetes insipidus, hearing loss, ataxia, anaemia and many others). This syndrome is caused by recessive mutations in the wolframin gene (WFS1) localized on chromosome 4p16.1. The aim of this study ...

Diabetes and the development of its complications have been associated with mitochondrial DNA (mtDNA) dysfunction, but causal relationships remain undetermined. With the objective of testing whether increased mtDNA mutations exacerbate the diabetic phenotype, we have compared mice heterozygous for the Akita diabetogenic mutation (Akita) with mice homozygous for the D257A ...

Simultaneous catabolic and anabolic glucose metabolism occurs in the same compartment during photomixotrophic growth of the model cyanobacterium Synechocystis sp. PCC 6803. The presence of glucose is stressful to the cells; it is reflected in the high frequency of suppression mutations in glucose-sensitive mutants. We show that glucose affects many ...

ABSTRACT: AIMS: Coronary artery disease (CAD) and stroke share a major linkage at the chromosome 12q24 locus. The same chromosome region entails at least a major risk gene for type 2 diabetes (T2D) within NIDDM2, the non-insulin-dependent-diabetes 2 locus. The gene of Proteasome Modulator 9 (PSMD9) lies in the NIDDM2 ...

The multiple physiological characterizations of glucagon-like peptide-1 (GLP-1) make it a promising drug candidate for the therapy of type 2 diabetes. However, the half-life of GLP-1 is short in vivo due to degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. This indicates that the stabilization of GLP-1 is critical for ...

Phosphoenolpyruvate-dependent glucose phosphorylation via the phosphotransferase system (PTS) is the major path of glucose uptake in Corynebacterium glutamicum, but some growth from glucose is retained in the absence of the PTS. The growth defect of a deletion mutant lacking the general PTS component HPr in glucose medium could be overcome ...