Insulin Resistance Is Better Estimated by Using Fasting Glucose, Lipid Profile, and Body Fat Percent Than by HOMA-IR in Japanese Patients with Type 2 Diabetes and Impaired Glucose Tolerance: An Exploratory Study.

Aims: The aim of the present study is to estimate insulin resistance (IR) using clinically available parameters except for serum insulin or C-peptide concentration to overcome the limitation of homeostasis model assessment of IR (HOMA-IR), which has been widely used in clinical practice. Patients and Methods: Fifty-two admitted patients with type 2 diabetes or impaired glucose tolerance were enrolled, and steady state plasma glucose (SSPG) method and cookie meal tolerance test were performed together with fasting blood sampling and anthropometric measurements. Insulin sensitivity measured by SSPG was estimated as glucose clearance corrected by the excretion of glucose into urine (C-GC). Results: Log-transformed (C-GC) was negatively correlated with fasting plasma glucose (FPG), log (Fasting triglyceride: TG), log (Fasting TG/Fasting high-density lipoprotein cholesterol: HDLC), and their area under the curves (AUCs). Fasting and AUC-HDLC was positively and fasting free fatty acid (FFA) was negatively correlated with log (C-GC). Body fat (%) was negatively correlated with log (C-GC). Multiple regression analysis on log (C-GC) as an outcome variable revealed that FPG, log (AUC-TG/AUC-HDLC), body fat (%), and fasting FFA were selected as significant predictive variables and contributed to log (C-GC) by 60% (adjusted R2). Replacing log (AUC-TG/AUC-HDLC) with its fasting value, log (Fasting TG/Fasting HDLC), this model still showed a strong contribution to log (C-GC) by 57% (adjusted R2). These contributions were stronger than those in log (HOMA-IR) (52.5%), log (Fasting C-peptide) (45.7%) to log (C-GC). Conclusions: It is plausible that our estimation for IR without the inclusion of plasma insulin concentration can be applied in Japanese patients whose HOMA-IR is not appropriately available. The model using fasting values is less complicated and could be the best way for the estimation of IR.

The BcsD subunit of type I bacterial cellulose synthase interacts dynamically with the BcsAB catalytic core complex.

Cellulose synthase has two distinct functions: synthesis of the cellulose molecule (polymerization) and assembling the synthesized cellulose chains into the crystalline microfibril (crystallization). In the type I bacterial cellulose synthase (Bcs) complex, four major subunits - BcsA, BcsB, BcsC and BcsD - work in a coordinated manner. This study showed that the crystallization subunit BcsD interacts with the polymerization complex BcsAB in two modes: direct protein-protein interactions and indirect interactions through the product cellulose. We hypothesized that the former and latter modes represent the basal and active states of type I bacterial cellulose synthase, respectively, and this dynamic behaviour of the BcsD protein regulates the crystallization process of cellulose chains.

Identification of changes in the microflora composition of Japanese horse mackerel (Trachurus japonicus) during storage to identify specific spoilageorganisms.

Japanese horse mackerel (Trachurus japonicus) is an important marine resource, and its loss and waste should be reduced. This study aimed to identify the changes in the microflora composition during storage and specific spoilage organisms (SSOs) in Japanese horse mackerel, for spoilage prevention. They were stored at either 20 °C or 4 °C aerobically, and the bacterial viable counts, concentration of total volatile basic nitrogen (TVB-N), and microflora composition for each group were analyzed. Samples stored at 20 °C for 48 h showed similar viable counts to those stored at 4 °C for 168 h; however, the TVB-N concentrations increased at 20 °C, but not at 4 °C. 16S rRNA metagenome analysis showed that Shewanella became dominant genus in the microflora regardless of the storage temperature. However, dominant amplicon sequence variants (ASVs), which are a more detailed classification level than the genus, differed depending on the storage temperatures; therefore, dominant ASVs at 20 °C were assumed to be potential SSOs. Shewanella sp. Strain NFH-SH190041, which was genetically closely related to the dominant ASVs at 20 °C, was isolated, and its spoilage ability was verified. The strain NFH-SH190041 may be considered a novel SSO of Japanese horse mackerel because its 16S rRNA sequence is clearly different from those of known species.

Structural snapshot of a glycoside hydrolase family 8 endo-ß-1,4-glucanase capturing the state after cleavage of the scissile bond.

Bacterial cellulose (BC), which is produced by bacteria, is a biodegradable and biocompatible natural resource. Because of its remarkable physicochemical properties, BC has attracted attention for the development and manufacture of biomedical and industrial materials. In the BC production system, the enzyme endo-ß-1,4-glucanase, which belongs to glycoside hydrolase family 8 (GH8), acts as a cleaner by trimming disordered cellulose fibers to produce high-quality BC. Understanding the molecular mechanism of the endo-ß-1,4-glucanase would help in developing a reasonable biosynthesis of BC. Nevertheless, all of the steps in the reaction of this endo-ß-1,4-glucanase are not clear. This study confirms the BC hydrolytic activity of the endo-ß-1,4-glucanase from the BC-producing bacterium Enterobacter sp. CJF-002 (EbBcsZ) and reports crystal structures of EbBcsZ. Unlike in previously reported GH8 endo-ß-1,4-glucanase structures, here the base catalyst was mutated (D242A) and the structure of this mutant bound to cellooligosaccharide [EbBcsZ(D242A)CPT] was analyzed. The EbBcsZ(D242A)CPT structure showed two cellooligosaccharides individually bound to the plus and minus subsites of EbBcsZ. The glucosyl unit in subsite -1 presented a distorted 5S1 conformation, a novel snapshot of a state immediately after scissile-bond cleavage. In combination with previous studies, the reaction process of endo-ß-1,4-glucanase is described and the ß-1,4-glucan-trimming mechanism of EbBcsZ is proposed. The EbBcsZ(D242A)CPT structure also showed an additional ß-1,4-glucan binding site on the EbBcsZ surface, which may help to accept the substrate.

Graves' Disease after Adrenalectomy for Cushing's Syndrome.

A 44-year-old woman presented with a 3-month history of back pain, gait disturbance, and insomnia. She had moon face and central obesity but no goiter. Cushing's syndrome due to left adrenal adenoma was diagnosed. She also had low triiodothyronine syndrome and central hypothyroidism. Treatment involved adrenalectomy followed by 30 mg/day of hydrocortisone. Inappropriate secretion of thyroid-stimulating hormone occurred postoperatively. She developed Graves' disease nine months postoperatively and was treated with methimazole. Excess glucocorticoids followed by their withdrawal may influence the hypothalamic-pituitary-thyroid axis and immune system. Therefore, a careful evaluation of the thyroid function and antibodies is important after surgery for Cushing's syndrome.

Bromocriptine as a Potential Glucose-lowering Agent for the Treatment of Prolactinoma with Type 2 Diabetes.

A 22-year-old Japanese woman consulted an endocrinologist due to persistent galactorrhea for the past 10 months. She had hyperprolacinemia and had previously been diagnosed with type 2 diabetes mellitus based on her glycohemoglobin level of 11.6%. After two months, she was admitted to our hospital and finally diagnosed with prolactinoma. For the treatment of prolactinoma, bromocriptine 2.5 mg/day was started. After seven days, her post-prandial blood glucose levels, homeostasis model assessment of insulin resistance and plasma C-peptide levels were significantly improved. These results indicate that traditional bromocriptine can be an effective therapeutic alternative in patients with prolactinoma complicated with type 2 diabetes.