Hypertension is associated with the reduction in epidermal small fibres independently of sural nerve inflammation in type 2 diabetic subjects.

Diabetic polyneuropathy (DPN) is a multifactorial disease associated not only with hyperglycaemia but also with circulatory disturbances such as hypertension. A close interaction between the immune system and hypertension is known. It remains unclear whether the inflammatory response is associated with hypertension in the pathology of human DPN.

A case of selpercatinib treatment for anaplastic thyroid carcinoma resulting in abscess formation.

Rearranged during transfection () gene abnormality is a driver gene mutation that causes thyroid cancer, and selpercatinib has been shown to be useful for treating thyroid cancer with gene abnormalities. Anaplastic thyroid cancer is a disease with an extremely poor prognosis with no standard treatment established, and there are only one case reports of the efficacy of selpercatinib for fusion gene-positive anaplastic thyroid cancer. We herein report our experience treating an old Japanese woman with unresectable anaplastic thyroid cancer with selpercatinib.

Contribution of animal models to diabetes research: Its history, significance, and translation to humans.

Diabetes mellitus is still expanding globally and is epidemic in developing countries. The combat of this plague has caused enormous economic and social burdens related to a lowered quality of life in people with diabetes. Despite recent significant improvements of life expectancy in patients with diabetes, there is still a need for efforts to elucidate the complexities and mechanisms of the disease processes to overcome this difficult disorder.

Gut as a source of new β-cells and Segi's cap.

A deficit of β-cells is a salient feature in both type 1 and type 2 diabetes mellitus. Due to the absolute lack of supplying β-cells for organ or cell transplantation, there is an urgent need to explore the efficient method to generate insulin-producing cells. Cell conversion of intestinal cryptic epithelial cells to insulin-producing β-like cells is a novel and promising therapeutic target.

Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus.

In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2A) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases.

RAGE activation in macrophages and development of experimental diabetic polyneuropathy.

It is suggested that activation of receptor for advanced glycation end products (RAGE) induces proinflammatory response in diabetic nerve tissues. Macrophage infiltration is invoked in the pathogenesis of diabetic polyneuropathy (DPN), while the association between macrophage and RAGE activation and the downstream effects of macrophages remain to be fully clarified in DPN. This study explored the role of RAGE in the pathogenesis of DPN through the modified macrophages.

The diversity and abundance of gut microbiota are associated with the pain sensation threshold in the Japanese population.

Small fibre neuropathy (SFN) is an initial pathology of diabetic polyneuropathy (DPN). Serum lipopolysaccharide binding protein levels are positively correlated with the pain threshold in the foot, suggesting that the abundance of gut Gram-negative bacilli, which are a source of lipopolysaccharides, may be involved in the development of DPN. Furthermore, the abundance of the gut and oral microbiota is assumed to be involved in the pathogenesis of diabetes.

Effective Treatment of Intraoperative Hiccups With Chlorpromazine Under General Anesthesia Without Muscle Relaxants: A Case Report.

Hiccups are common reflexes and many treatment methods have been reported. Chlorpromazine is a known treatment option for hiccups, but its efficacy under general anesthesia remains unclear. We report the case of a patient with vagal schwannoma who developed hiccups while under general anesthesia.

Diabetes in Humans Activates Pancreatic Stellate Cells via RAGE in Pancreatic Ductal Adenocarcinoma.

Pancreatic stellate cells (PSCs) mainly consist of cancer-associating fibroblasts in pancreatic ductal adenocarcinoma (PDAC). The receptor for advanced glycation end products (RAGE) is implicated in the pathophysiology of diabetic complications. Here, we studied the implication of RAGE in PSC activation in PDAC.

Immunohistochemical detection of enteroviruses in pancreatic tissues of patients with type 1 diabetes using a polyclonal antibody against 2A protease of Coxsackievirus.

Aims/introduction: The need for antiserum for immunohistochemical (IHC) detection of enterovirus (EV) in formaldehyde-fixed and paraffin-embedded samples is increasing. The gold standard monoclonal antibody (clone 5D8/1) against EV-envelope protein (VP1) was proven to cross-react with other proteins. Another candidate marker of EV proteins is 2A protease (2A ), which is encoded by the EV gene and translated by the host cells during EV replication, and participates processing proproteins to viral capsid proteins.

Islet microangiopathy and augmented β-cell loss in Japanese non-obese type 2 diabetes patients who died of acute myocardial infarction.

Aims/introduction: Islets have microvessels that might develop pathological alterations similar to microangiopathy in type 2 diabetes patients. It remains unclear, however, whether the changes correlate with endocrine cell deficits or whether the presence of macroangiopathy influences the islet microvasculature in Japanese type 2 diabetes patients. In this study, we characterized changes of the islet microvessels and endocrine cells in Japanese non-obese patients with type 2 diabetes who died of acute myocardial infarction (AMI).

Inhibitory effects of xanthine oxidase inhibitor, topiroxostat, on development of neuropathy in db/db mice.

Inflammation and oxidative stress contribute to the pathophysiology of diabetic neuropathy. According to recent evidence, the modulation of macrophage polarization in peripheral nerves represents a potential therapeutic target for diabetic neuropathy. Xanthine oxidase, which is a form of xanthin oxidoreductase, is the rate-limiting enzyme that catalyzes the degradation of hypoxanthine and xanthine into uric acid.

Role of glucosamine in development of diabetic neuropathy independent of the aldose reductase pathway.

Long-term metabolic aberrations contribute to the development of diabetic neuropathy but the precise mechanism or mechanisms remains elusive. We have previously shown that aldose reductase-deficient mice exhibit delayed onset and progression of neuropathy following induction of diabetes, suggesting a role both for downstream metabolites of this enzyme and also for other unrelated pathways. In this study, we have utilized comprehensive metabolomics analyses to identify potential neurotoxic metabolites in nerve of diabetic mice and explored the mechanism of peripheral nerve injury.

Increased Oxidative Stress Underlies Abnormal Pain Threshold in a Normoglycemic Japanese Population.

Normal-high HbA1c levels are a risk factor for attenuated pain sensation in normoglycemic subjects. It is unclear, however, what mechanisms underlie the pathogenesis of attenuated pain sensation in such a population. We, therefore, explored the relationship between oxidative stress (OS) and pain sensation in a rural Japanese population.

Lipopolysaccharide-binding protein is a distinctive biomarker of abnormal pain threshold in the general Japanese population.

Introduction: Small fiber neuropathy (SFN) is an early manifestation in diabetic polyneuropathy (DPN); however, the mechanisms are not fully understood. In diabetes, SFN is presumed to be common in individuals with overt DPN, enhancing activation of polyol pathway, oxidative stress, advanced glycation end products (AGEs), and inflammation. We explored the relationship between clinicohematological factors related to DPN and pain sensation in the Japanese population.

What can we learn from the islet of Joslin Medalists?

This commentary refers to the recent study of Joslin Medalists that showed evidence of residual endocrine cells still functioning in response to glucose stimuli. Islet pathology showed the ongoing remodeling influenced by autoimmune attack and glucose toxicity. The results showed the presence of functional endocrine cells that contribute to the longevity of patients with type 1 diabetes.

Beneficial effects of combination therapy of canagliflozin and teneligliptin on diabetic polyneuropathy and β-cell volume density in spontaneously type 2 diabetic Goto-Kakizaki rats.

Aims: Parasympathetic nerve (PN) signaling plays a crucial role in the maintenance of pancreatic β-cell volume density (V). PN may be pathologically affected in diabetic polyneuropathy (DPN). However, the association between the reduction of PNs in islets and V and the therapeutic effects of a DPP4 inhibitor (DPP4i) and an SGLT2 inhibitor (SGLT2i) in nonobese type 2 diabetes mellitus (T2DM) Goto-Kakizaki rats (GK) have not been investigated.

Corrigendum: Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

[This corrects the article DOI: 10.3389/fendo.2019.

Diabetes, an independent poor prognostic factor of non-B non-C hepatocellular carcinoma, correlates with dihydropyrimidinase-like 3 promoter methylation.

A concurrent increase in the prevalence of hepatocellular carcinoma (HCC) with that of type 2 diabetes (T2D) and obesity has been reported in the absence of hepatitis B virus surface antigen-negative/hepatitis C virus antibody-negative HCC (NBNC-HCC). However, the prognostic relevance of this association remains unclear. Promoter methylation (PM) of the dihydropyrimidinase-like 3 gene (DPYSL3) has been implicated in virus-related HCC.

Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

Small fiber dysfunction is common in subjects with diabetic polyneuropathy (DPN). It is unsettled, however, whether marginal glucose intolerance is implicated in the onset and progression of small fiber dysfunction. Herein, we explored the relationship between glycated hemoglobin levels (HbA1c) and pain sensation in the Japanese population.

Unique Inflammatory Changes in Exocrine and Endocrine Pancreas in Enterovirus-Induced Fulminant Type 1 Diabetes.

Context: There are scant reports on the pathological changes of the exocrine and endocrine pancreas in fulminant type 1 diabetes mellitus (FT1DM).

Objective: To clarify the distinct pathological changes in the exocrine as well as the endocrine pancreas shortly after onset of diabetes in FT1DM.

Design: The exocrine and endocrine pancreases of 3 patients with FT1DM and 17 nondiabetic controls were immunohistochemically examined for islet and exocrine tissue inflammation, infiltrating mononuclear cell (MNC) CD subtype, enterovirus capsid protein 1 (VP1) localization, and CXC chemokine ligand 10 (CXCL10) and CXC chemokine receptor 3 (CXCR3) expressions.

Cutaneous microangiopathy in patients with type 2 diabetes: Impaired vascular endothelial growth factor expression and its correlation with neuropathy, retinopathy and nephropathy.

Aims/introduction: To examine the three-dimensional morphology and vascular endothelial growth factor (VEGF) expression of skin microvasculature in patients with type 2 diabetes in relation to neuropathy, retinopathy and nephropathy.

Materials And Methods: The present study enrolled 17 individuals with type 2 diabetes and 16 without. Skin sections were double-immunostained for type IV collagen and VEGF-A or protein gene product 9.

Distinct Inflammatory Changes of the Pancreas of Slowly Progressive Insulin-dependent (Type 1) Diabetes.

Objective: The aim of this study was to identify the distinct pathological changes on the endocrine and exocrine pancreas of slowly progressive insulin-dependent diabetes mellitus (SPIDDM) or latent autoimmune diabetes in adults.

Methods: The pancreases from 12 islet autoantibody-positive SPIDDM patients and 19 age-matched subjects with no diabetes were examined histologically for islet inflammation/insulitis, expressions of cytokines, and enterovirus VP1 protein, exocrine pancreatic inflammation, pancreatic ductal changes, major histocompatibility complex class I hyperexpression, and amylin-positive amyloid in the islets.

Results: Insulitis dominant for CD8 T-cells and CD68 macrophages was observed in all SPIDDM cases irrespective of duration of diabetes and weight of residual beta cells.

Crucial role of Reg I from acinar-like cell cluster touching with islets (ATLANTIS) on mitogenesis of beta cells in EMC virus-induced diabetic mice.

Recently, we reported the presence of distinct cell clusters named acinar-like cell clusters touching Langerhans islets with thin interstitial surrounding (ATLANTIS) in human pancreas. A morphological study in humans demonstrated that ATLANTIS and islet cell clusters are found together in the microenvironment enclosed by a common basement membrane, and ATLANTIS releases vesicles containing Regenerating gene protein (REG Iα) to islet cell clusters. We examined 1) the presence or absence of ATLANTIS in homozygous Reg I (mouse homologue of human REG Iα) deficient (Reg I) and wild-type mice, and 2) the possible role of ATLANTIS in the regeneration of beta cell clusters after encephalomyocarditis (EMC) virus (D-variant) infection in Reg I and wild-type mice.