First Japanese Family With -MODY (MODY4): A Novel Frameshift Mutation, Clinical Characteristics, and Implications.

Context: The gene encodes pancreatic and duodenal homeobox, a critical transcription factor for pancreatic β-cell differentiation and maintenance of mature β-cells. Heterozygous loss-of-function mutations cause -MODY (MODY4).

Case Description: Our patient is an 18-year-old lean man who developed diabetes at 16 years of age.

Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report.

Background: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions.

Case Presentation: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities.

L-Arginine prevents cereblon-mediated ubiquitination of glucokinase and stimulates glucose-6-phosphate production in pancreatic β-cells.

We sought to determine a mechanism by which L-arginine increases glucose-stimulated insulin secretion (GSIS) in β-cells by finding a protein with affinity to L-arginine using arginine-immobilized magnetic nanobeads technology. Glucokinase (GCK), the key regulator of GSIS and a disease-causing gene of maturity-onset diabetes of the young type 2 (MODY2), was found to bind L-arginine. L-Arginine stimulated production of glucose-6-phosphate (G6P) and induced insulin secretion.

Clinical manifestations of a sporadic maturity-onset diabetes of the young (MODY) 5 with a whole deletion of HNF1B based on 17q12 microdeletion.

We report a sporadic case of maturity-onset diabetes of the young type 5 (MODY5) with a whole-gene deletion of the hepatocyte nuclear factor-1beta (HNF1B) gene. A 44-year-old Japanese man who had been diagnosed with early-onset non-autoimmune diabetes mellitus at the age of 23 was examined. He showed multi-systemic symptoms, including a solitary congenital kidney, pancreatic hypoplasia, pancreatic exocrine dysfunction, elevation of the serum levels of liver enzymes, hypomagnesemia, and hyperuricemia.

Evaluation of the Diabetes Regional Coordination Path using the Diabetes Coordination Notebook in community-based diabetes care.

Aims: A number of epidemiologic surveys have demonstrated that improving lifestyle habits, providing patient education, and regular screening of patients for early diabetic symptoms and complications through multidisciplinary collaboration are crucial for the management of diabetes.

Methods: To evaluate the Diabetes Coordination Notebook and the Diabetes Regional Coordination Path in management of diabetes, 217 community pharmacies conducted a survey by questionnaire in Gifu Prefecture, Japan.

Results: A reply to the questionnaire was obtained from 27,016 individuals, of whom 5,572 claimed to have diabetes or prediabetes.

Periodontal Disease May be Associated With the Occurrence of Diabetic Retinopathy: A Subgroup Analysis of The Survey of the Diabetes Coordination Notebook in Gifu.

Aims: A questionnaire survey of the prevalence of diabetic retinopathy was recently conducted in Japan. A subgroup analysis to examine the association of periodontal disease with diabetic retinopathy in subjects with diabetes and prediabetes was conducted.

Methods: The association of the presence of periodontal disease with the occurrence of diabetic retinopathy was examined using multivariate logistic regression analysis.

Genetic Dissection and Clinical Features of MODY6 (NEUROD1-MODY).

Purpose Of Review: MODY6 due to mutations in the gene NEUROD1 is very rare, and details on its clinical manifestation and pathogenesis are scarce. In this review, we have summarized all reported cases of MODY6 diagnosed by genetic testing, and examined their clinical features in detail.

Recent Findings: MODY6 is a low penetrant MODY, suggesting that development of the disease is affected by genetic modifying factors, environmental factors, and/or the effects of interactions of genetic and environmental factors, as is the case with MODY5.

No novel, high penetrant gene might remain to be found in Japanese patients with unknown MODY.

MODY 5 and 6 have been shown to be low-penetrant MODYs. As the genetic background of unknown MODY is assumed to be similar, a new analytical strategy is applied here to elucidate genetic predispositions to unknown MODY. We examined to find whether there are major MODY gene loci remaining to be identified using SNP linkage analysis in Japanese.

Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitor as an Add-on Drug to GLP-1 Receptor Agonists for Glycemic Control of a Patient with Prader-Willi Syndrome: A Case Report.

Introduction: Diabetes patients with Prader-Willi syndrome (PWS) are obese because of hyperphagia; weight control by dietary modification and medicine is required for glycemic control. There are several recent reports showing the effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in PWS.

Case Report: A 36-year-old Japanese male patient was diagnosed with PWS at 10 years of age.

NEUROD1-deficient diabetes (MODY6): Identification of the first cases in Japanese and the clinical features.

Aims: Only a few families with neuronal differentiation 1 (NEUROD1)-deficient diabetes, currently designated as maturity-onset diabetes of the young 6 (MODY6), have been reported, but mostly in Caucasian, and no mutation has been identified by family-based screening in Japanese. Accordingly, the phenotypic details of the disease remain to be elucidated.

Methods: We examined a total of 275 subjects having diabetes suspected to be MODY who were negative for mutations in MODY1-5 referred from 155 medical institutions throughout Japan.

A first case of adrenomyeloneuropathy with mutation Y174S of the adrenoleukodystrophy gene.

The patient first noticed spasticity and weakness in his legs. He was diagnosed with chronic myelogenous leukemia (CML); the symptoms were attributed to neuropathy associated with CML. By treatment with dasatinib, he achieved complete hematological remission, but his difficulty in walking was not improved.

Association of genetic variants of the incretin-related genes with quantitative traits and occurrence of type 2 diabetes in Japanese.

Background: None of the high frequency variants of the incretin-related genes has been found by genome-wide association study (GWAS) for association with occurrence of type 2 diabetes in Japanese. However, low frequency and rare and/or high frequency variants affecting glucose metabolic traits remain to be investigated.

Method: We screened all exons of the incretin-related genes (, , , , , and ) in 96 patients with type 2 diabetes and investigated for association of genetic variants of these genes with quantitative metabolic traits upon test meal with 38 young healthy volunteers and with the occurrence of type 2 diabetes in Japanese subjects comprising 1303 patients with type 2 diabetes and 1014 controls.

Screening of diabetes of youth for hepatocyte nuclear factor 1 mutations: clinical phenotype of HNF1β-related maturity-onset diabetes of the young and HNF1α-related maturity-onset diabetes of the young in Japanese.

Aim: To compare the prevalence and clinical features of HNF1β-related MODY and HNF1α-related MODY in Japanese.

Methods: We enrolled 230 Japanese patients with suspected MODY and examined them for HNF1α and HNF1β mutations. We characterized the clinical features of HNF1β-related MODY (HNF1β-MODY) and HNF1α-related MODY (HNF1α-MODY).

Molecular and catalytic properties of 2,4'-dihydroxyacetophenone dioxygenase from Burkholderia sp. AZ11.

The gene dad encoding 2,4'-dihydroxyacetophenone (DHAP) dioxygenase was cloned from Burkholderia sp. AZ11. The initiation codon GTG was converted to ATG for high-level expression of the enzyme in Escherichia coli.

Synergistic effect of α-glucosidase inhibitors and dipeptidyl peptidase 4 inhibitor treatment.

Monotherapy of α-glucosidase inhibitor (α-GI) or dipeptidyl peptidase 4 (DPP4) inhibitor does not sufficiently minimize glucose fluctuations in the diabetic state. In the present study, we evaluated the combined effects of various of α-GI inhibitors (acarbose, voglibose or miglitol) and sitagliptin, a DPP4 inhibitor, on blood glucose fluctuation, insulin and active glucagon-like peptide-1 (GLP-1) levels after nutriment loading in mice. Miglitol and sitagliptin elicited a 47% reduction (P < 0.

[Association between polymorphisms of TCF7L2 and type 2 diabetes with special reference to incretin action].

TCF7L2 is a Wnt signaling-associated transcription factor and is ubiquitously expressed. Polymorphisms in the TCF7L2 gene exhibit the strongest association with type 2 diabetes among approximately twenty susceptibility gene variants identified to date. Although the mechanisms by which TCF7L2 affects susceptibility to type 2 diabetes remain to be elucidated, several studies have shown that decreased TCF7L2 protein inhibits the insulin secretory response to oral glucose through impaired incretin action(GLP-1, GIP).

Predictive factors for pain relief after endoscopic ultrasound-guided celiac plexus neurolysis.

Background: Celiac plexus neurolysis (CPN) is an established treatment for upper abdominal cancer pain. Recently, endoscopic ultrasound-guided CPN (EUS-CPN) was introduced and has enabled the performance of CPN under real-time imaging guidance, thereby making this technique much safer and easier. However, this procedure is not always efficacious, and a limited number of patients benefit from it.

Endoscopic ultrasound-guided fine-needle aspiration in patients with lymphadenopathy suspected of recurrent malignancy after curative treatment.

Background: The diagnosis of lymphadenopathy after treatment of malignancy is sometimes difficult, especially in patients whose treatment was deemed curative and without local recurrence or those who have increased serum levels of related tumor markers. We aimed to evaluate the effectiveness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a diagnostic tool in patients with lymphadenopathy after curative treatment of malignancy.

Methods: Consecutive patients with mediastinal, intraabdominal, or pelvic lymphadenopathy after curative treatment of malignancy who were referred to our hospital between October 2003 and September 2007 were enrolled in this study.

Identification of minimal promoter and genetic variants of Kruppel-like factor 11 gene and association analysis with type 2 diabetes in Japanese.

Genetic analysis of the KLF11 gene revealed two rare variants, A347S and T220M, segregating in families with early-onset type 2 diabetes, and one frequent polymorphic Q62R variant significantly associated with type 2 diabetes in Northern Europeans. Furthermore, it has been reported that over-expression of KLF11 has a deleterious effect on insulin promoter activity. Thus, an altered expression level of KLF11 may contribute to the occurrence of type 2 diabetes.

Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients.

Mutations in the small heterodimer partner gene (NR0B2; alias SHP) are associated with high birth weight and mild obesity in Japanese children. SHP mutations may also be associated with later obesity and insulin resistance syndrome that induces diabetes. To investigate this possibility, the prevalence of SHP mutations in Japanese with and without type 2 diabetes mellitus and the functional properties of the mutant proteins were evaluated.

Case report of familial Carney complex due to novel frameshift mutation c.597del C (p.Phe200LeufsX6) in PRKAR1A.

Carney complex is an autosomal dominantly inherited disease characterized by skin pigmentation, myxoma, primary pigmented nodular adrenocortical disease (PPNAD), and acromegaly. However, only a few incidences of PPNAD combined with acromegaly are observed in patients. The type 1alpha regulatory subunit of cAMP-dependent protein kinase (PRKAR1A) has been identified in patients as a causative gene for Carney complex by a positional cloning approach.

Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan.

Background: In Europeans and populations of European origin, several groups have recently identified novel type 2 diabetes susceptibility genes, including FTO, SLC30A8, HHEX, CDKAL1, CDKN2B, and IGF2BP2, none of which were in the list of functional candidates.

Objective And Design: The aim of this study was to replicate in a Japanese population previously identified associations of single nucleotide polymorphisms (SNPs) within 10 candidate loci with type 2 diabetes using a relatively large sample size: 1921 subjects with type 2 diabetes and 1622 normal controls.

Results: A total of 15 SNPs were genotyped.

Intraductal chilled saline perfusion to prevent bile duct injury during percutaneous radiofrequency ablation for hepatocellular carcinoma.

Background And Aim: Radiofrequency ablation (RFA) is a promising, minimally invasive treatment for hepatocellular carcinoma (HCC). However, thermal injury sometimes occurs in the bile duct, potentially leading to a critical situation. The aim of the present study was to investigate whether bile duct injury is reduced by an intraductal chilled saline perfusion (ICSP) through a nasobiliary tube during RFA for HCC.