C-Mannosyl tryptophan is a novel biomarker for thrombocytosis of myeloproliferative neoplasms.

C-Mannosyl tryptophan (CMW), a unique glycosylated amino acid, is considered to be produced by degradation of C-mannosylated proteins in living organism. Although protein C-mannosylation is involved in the folding and secretion of substrate proteins, the pathophysiological function in the hematological system is still unclear. This study aimed to assess CMW in the human hematological disorders.

Profiling of Unfolded Protein Response Markers and Effect of IRE1α-specific Inhibitor in Pituitary Neuroendocrine Tumor.

Context: Inositol-requiring enzyme 1α (IRE1α) and PKR-like ER kinase (PERK), which are endoplasmic reticulum (ER) membrane proteins, regulate the unfolded protein response (UPR). These molecules have recently gained attention as a novel therapeutic target in secretory tumors. The roles of the UPR in pituitary neuroendocrine tumors (PitNETs) are unclear.

Renoprotective potential of concomittant medications with SGLT2 inhibitors and renin-angiotensin system inhibitors in diabetic nephropathy without albuminuria: a retrospective cohort study.

The renal protective effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors and renin-angiotensin system (RAS) inhibitors on diabetic nephropathy without albuminuria have not been fully investigated. This retrospective cohort study focused on patients with type 2 diabetes mellitus who had a baseline estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m, and a urinary albumin-to-creatinine ratio < 30 mg/gCr.

Thyroid function, glycemic control, and diabetic nephropathy in patients with type 2 diabetes over 24 months: prospective observational study.

Background: The higher prevalence of thyroid dysfunction in type 1 diabetes patients has been well established, whereas it is a matter of debate whether that is also observed in type 2 diabetes patients. This study was conducted to reveal whether higher prevalence of thyroid dysfunction is observed in patients with type 2 diabetes.

Methods: We examined thyroid functions and thyroid autoantibodies in 200 patients with type 2 diabetes and 225 controls, with 24 months follow up for those with type 2 diabetes.

Effect of SARS-CoV-2 BNT162b2 mRNA vaccine on thyroid autoimmunity: A twelve-month follow-up study.

Objectives: Graves' disease (GD) has been highlighted as a possible adverse effect of the respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine. However, it is unknown if the SARS-CoV-2 vaccine disrupts thyroid autoimmunity. We aimed to present long-term follow-up of thyroid autoimmunity after the SARS-CoV-2 BNT162b2 mRNA vaccine.

Reduced Fat Taste Sensitivity in Obese Japanese Patients and Its Recovery after a Short-Term Weight Loss Program.

Fat taste has recently attracted attention as the 'sixth taste.' However, the relationship between fat and sweet taste in Japanese obesity has not yet been examined, and no reports have ascertained whether improvement of fat taste can be obtained by weight loss. Patients were recruited into obesity group (BMI≥30 kg/m; n=15) or control group (BMI<25 kg/m; n=11).

Allosteric Inhibition of c-Abl to Induce Unfolded Protein Response and Cell Death in Multiple Myeloma.

Endoplasmic reticulum stress activates inositol-requiring enzyme 1α (IRE1α) and protein kinase, R-like endoplasmic reticulum kinase (PERK), the two principal regulators of the unfolded protein response (UPR). In multiple myeloma, adaptive IRE1α signaling is predominantly activated and regulates cell fate along with PERK. Recently, we demonstrated that GNF-2, an allosteric c-Abl inhibitor, rheostatically enhanced IRE1α activity and induced apoptosis through c-Abl conformational changes in pancreatic β cells.

Soluble T-cadherin promotes pancreatic β-cell proliferation by upregulating Notch signaling.

Endogenous humoral factors that link systemic and/or local insulin demand to pancreatic β-cells have not been identified. Here, we demonstrated that T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin primarily expressed in vascular endothelial cells and cardiac and skeletal muscle cells, but not in pancreatic β-cells, was secreted as soluble forms and was important for β-cell proliferation. (T-cadherin) knockout mice exhibited impaired glucose handling due to attenuated β-cell proliferation under high-fat diet conditions.

Isolated ACTH deficiency following immunization with the BNT162b2 SARS-CoV-2 vaccine: a case report.

Background: The global COVID-19 pandemic requires urgent development of new vaccines. Endocrinological adverse effects following the new mRNA vaccine against COVID-19 have been reported in several cases. Specific to the involvement of pituitary function; however, only a single case with hypophysis has been reported.

Molecular Mechanism of Pancreatic β-Cell Failure in Type 2 Diabetes Mellitus.

Various important transcription factors in the pancreas are involved in the process of pancreas development, the differentiation of endocrine progenitor cells into mature insulin-producing pancreatic β-cells and the preservation of mature β-cell function. However, when β-cells are continuously exposed to a high glucose concentration for a long period of time, the expression levels of several insulin gene transcription factors are substantially suppressed, which finally leads to pancreatic β-cell failure found in type 2 diabetes mellitus. Here we show the possible underlying pathway for β-cell failure.

Hypopituitarism and cranial nerve involvement mimicking Tolosa-Hunt syndrome as the initially presenting feature of diffuse large B-cell lymphoma: a case report.

Background: Early diagnosis of lymphoma involving the central nervous system is sometimes difficult but emergent to avoid the delay of therapeutic initiation. Pituitary insufficiencies are usually associated with lymphoma in the pituitary gland. There have been no cases of lymphoma originating from extra pituitary gland with hypopituitarism that simultaneously presenting unilateral upper cranial nerve palsies and ophthalmalgia.

Spatial and transcriptional heterogeneity of pancreatic beta cell neogenesis revealed by a time-resolved reporter system.

Aims/hypothesis: While pancreatic beta cells have been shown to originate from endocrine progenitors in ductal regions, it remains unclear precisely where beta cells emerge from and which transcripts define newborn beta cells. We therefore investigated characteristics of newborn beta cells extracted by a time-resolved reporter system.

Methods: We established a mouse model, 'Ins1-GFP; Timer', which provides spatial information during beta cell neogenesis with high temporal resolution.

Correction to: Glycemic control of people with diabetes over months after the 2018 North Osaka Earthquake.

[This corrects the article DOI: 10.1007/s13340-020-00438-6.].

Characterisation of Ppy-lineage cells clarifies the functional heterogeneity of pancreatic beta cells in mice.

Aims/hypothesis: Pancreatic polypeptide (PP) cells, which secrete PP (encoded by the Ppy gene), are a minor population of pancreatic endocrine cells. Although it has been reported that the loss of beta cell identity might be associated with beta-to-PP cell-fate conversion, at present, little is known regarding the characteristics of Ppy-lineage cells.

Methods: We used Ppy-Cre driver mice and a PP-specific monoclonal antibody to investigate the association between Ppy-lineage cells and beta cells.

Psychosocial conditions and the progression of diabetic nephropathy in Japanese with type 2 diabetes mellitus.

We previously reported the association of positive psychosocial conditions with diabetic nephropathy (DN) in patients with type 2 diabetes in a cross-sectional setting. In the present study, we evaluated the association between six indicators related to psychosocial conditions and the progression of DN assessed by estimated glomerular filtration rate (eGFR) and albuminuria during 2-year observation period in 252 patients with type 2 diabetes. In unadjusted model, the subjects with higher happiness score attenuated reduced eGFR, and those with more social support attenuated increase in alubuminuria and decline eGFR.

Association of abdominal obesity with crossing capillaries in the finger nailfold in type 2 diabetes mellitus.

Aim: Increased crossing of finger nailfold capillaries could be a novel visual marker of early microvascular damage among type 2 diabetes mellitus patients. Although abdominal obesity is an important driver of early microvascular damage, its association with an increase in the percentage of crossing capillaries remains uncertain. We investigated the association between abdominal obesity and an increase in the percentage of crossing capillaries in the finger nailfold in patients with type 2 diabetes mellitus.

Evaluation of change in metabolome caused by comprehensive diabetes treatment: A prospective observational study of diabetes inpatients with gas chromatography/mass spectrometry-based non-target metabolomic analysis.

Aims/introduction: Diabetes patients develop a variety of metabolic abnormalities in addition to hyperglycemia. However, details regarding change in various metabolites after comprehensive diabetes treatment remain unknown. This study aimed to identify the short-term change in metabolome in inpatients who were subject to comprehensive diabetes treatment, using gas chromatography/mass spectrometry-based non-target metabolomics techniques.

Glucotoxicity-induced suppression of Cox6a2 expression provokes β-cell dysfunction via augmented ROS production.

Oxidative stress is a deteriorating factor for pancreatic β-cells under chronic hyperglycemia in diabetes. However, the molecular mechanism underlying the increase in oxidative stress in β-cells under diabetic conditions remains unclear. We demonstrated previously that the selective alleviation of glucotoxicity ameliorated the downregulation of several β-cell factors, including Cox6a2.

Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors facilitate urine glucose excretion by reducing glucose reabsorption, leading to ameliorate glycemic control. While the main characteristics of type 2 diabetes mellitus are insufficient insulin secretion and insulin resistance, SGLT2 inhibitors have some favorable effects on pancreatic β-cell function and insulin sensitivity. SGLT2 inhibitors ameliorate fatty liver and reduce visceral fat mass.

Association of obesity, diabetes, and physical frailty with dental and tongue-lip motor dysfunctions in patients with metabolic disease.

Objective: This study aimed to reveal the clinical features associated with decreased dental (or shearing/crushing) and tongue-lip motor functions in patients with metabolic diseases.

Methods: One thousand patients with metabolic diseases including diabetes, dyslipidemia, hypertension, and hyperuricemia were recruited. Dental function was assessed with a gummy jelly test, wherein glucose elution from a chewed gummy jelly was measured.

Coincidence of Large Adrenal Cyst and Prominent Hyporeninemic Hyperaldosteronism.

A 67-year-old Japanese woman who had end-stage renal disease was referred to our hospital for kidney transplantation. Abdominal CT revealed a large adrenal mass with inhomogeneity. She had a history of hospitalization for stroke and heart failure and exhibited prominent hyporeninemic hyperaldosteronism.

Glycemic control of people with diabetes over months after the 2018 North Osaka Earthquake.

Objective: On June 18 2018, Japan experienced the North Osaka Earthquake. The shaking intensity was recorded as level 6 of the Japan Meteorological Agency Seismic Intensity Scale. Despite the severe shaking, damages of lifelines and transportation networks were limited, and they were completely recovered within several days.

Preoperative fundus examination in patients with diabetes scheduled for surgery.

This study aimed to show the proportion of fundus examinations in patients with diabetes who were scheduled for surgery. We retrospectively analyzed 455 consecutive patients with diabetes admitted for surgery. Just 49% had fundus examinations before hospitalization.

Investigation of the Effect of Canagliflozin on the Disposition Index, a Marker of Pancreatic Beta Cell Function, in Patients with Type 2 Diabetes.

Aim: Our aim was to investigate the effects of add-on canagliflozin with glimepiride dose adjustment or glimepiride dose adjustment on pancreatic beta cell function in patients with type 2 diabetes mellitus and inadequate glycemic control despite stable triple therapy (metformin, teneligliptin, and glimepiride) plus diet/exercise therapy.

Methods: Forty patients on stable triple therapy were randomized to glimepiride dose adjustment without (glimepiride group) or with add-on canagliflozin 100 mg (canagliflozin group) for 24 weeks. The glimepiride dose was adjusted every 4 weeks based on continuous glucose monitoring over the previous 2 weeks according to a prespecified algorithm.