Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.

Autophagy is an essential quality control mechanism for maintaining organellar functions in eukaryotic cells. Defective autophagy in pancreatic beta cells has been shown to be involved in the progression of diabetes through impaired insulin secretion under glucolipotoxic stress. The underlying mechanism reveals the pathologic role of the hyperactivation of mechanistic target of rapamycin (mTOR), which inhibits lysosomal biogenesis and autophagic processes.

CDN1163, an activator of sarco/endoplasmic reticulum Ca ATPase, up-regulates mitochondrial functions and protects against lipotoxicity in pancreatic β-cells.

Background And Purpose: High levels of Ca in the endoplasmic reticulum (ER), established by the sarco/endoplasmic reticulum Ca ATPase (SERCA), are required for protein folding and cell signalling. Excessive ER Ca release or decreased SERCA activity induces unfolded protein accumulation and ER stress in pancreatic β-cells, leading to defective insulin secretion and diabetes. Here we have investigated the consequences of enhancing ER Ca uptake on β-cell survival and function.

Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane.

The activation of G Protein-Coupled Receptor 56 (GPR56), also referred to as Adhesion G-Protein-Coupled Ceceptor G1 (ADGRG1), by Collagen Type III (Coll III) prompts cell growth, proliferation, and survival, among other attributes. We investigated the signaling cascades mediating this functional effect in relation to the mitochondrial outer membrane voltage-dependent anion Channel-1 (VDAC1) expression in pancreatic β-cells. GPR56KD attenuated the Coll III-induced suppression of P70S6K, JNK, AKT, NFκB, STAT3, and STAT5 phosphorylation/activity in INS-1 cells cultured at 20 mM glucose (glucotoxicity) for 72 h.

Islet Gene View-a tool to facilitate islet research.

Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues.

Pathophysiology of type 2 diabetes and the impact of altered metabolic interorgan crosstalk.

Diabetes is a complex and multifactorial disease that affects millions of people worldwide, reducing the quality of life significantly, and results in grave consequences for our health care system. In type 2 diabetes (T2D), the lack of β-cell compensatory mechanisms overcoming peripherally developed insulin resistance is a paramount factor leading to disturbed blood glucose levels and lipid metabolism. Impaired β-cell functions and insulin resistance have been studied extensively resulting in a good understanding of these pathways but much less is known about interorgan crosstalk, which we define as signaling between tissues by secreted factors.

Elevated circulating follistatin associates with an increased risk of type 2 diabetes.

The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.

Infection of expanded polytetrafluoroethylene and Dacron-coated stents with : an experimental study in pigs.

Background: Diagnosis of the etiologic agent of endoprosthesis infections is essential to enable treatment, since these infections constitute important complications of endovascular procedures. Sonication of explanted tissue and materials is a technique that can be used to facilitate detection of biofilm-producing bacteria.

Objectives: To evaluate infection of pigs' aortas after implantation of nitinol stents coated with polytetrafluoroethylene (ePTFE) or Dacron, previously infected with biofilm-producing .

PHMB-loaded PDMS and its antimicrobial properties for biomedical applications.

Given the global panorama of demands in the health area, the development of biomaterials becomes irreducible for the maintenance and/or improvement in the quality of life of the human being. Aiming to reduce the impacts related to infections in the healing processes of the dermal structure, the present work proposes the development of polydimethylsiloxane (PDMS) based membranes with the incorporated polyhexamethylenebiguanide (PHMB) antimicrobial agent. In the present study, the antimicrobial and antibiofilm properties of polydimethylsiloxane (PDMS) films incorporated with 0.

Voices: Insulin and beyond.

Marking insulin's centennial, we share stories of researchers and clinicians whose seminal work has advanced our understanding of insulin, islet biology, insulin resistance, and diabetes. The past century of pursuing the "hormone of hormones" and advancing diabetes therapies is replete with stories of collaboration, perseverance, and triumph.

Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors.

Dopamine (DA) and norepinephrine (NE) are catecholamines primarily studied in the central nervous system that also act in the pancreas as peripheral regulators of metabolism. Pancreatic catecholamine signaling has also been increasingly implicated as a mechanism responsible for the metabolic disturbances produced by antipsychotic drugs (APDs). Critically, however, the mechanisms by which catecholamines modulate pancreatic hormone release are not completely understood.

Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells.

Aims/hypothesis: In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells during chronic glucose stress.

Methods: Respiration and cytosolic ATP changes were measured in human islet cell clusters after culture for 4 days in 11.

Potential Protection Against Type 2 Diabetes in Obesity Through Lower CD36 Expression and Improved Exocytosis in β-Cells.

Obesity is a risk factor for type 2 diabetes (T2D); however, not all obese individuals develop the disease. In this study, we aimed to investigate the cause of differential insulin secretion capacity of pancreatic islets from donors with T2D and non-T2D (ND), especially obese donors (BMI ≥30 kg/m). Islets from obese donors with T2D had reduced insulin secretion, decreased β-cell exocytosis, and higher expression of fatty acid translocase CD36.

Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance Hemodialysis.

Background And Objectives: Higher fruit and vegetable intake is associated with lower cardiovascular and all-cause mortality in the general population. It is unclear whether this association occurs in patients on hemodialysis, in whom high fruit and vegetable intake is generally discouraged because of a potential risk of hyperkalemia. We aimed to evaluate the association between fruit and vegetable intake and mortality in hemodialysis.

Oral mucosal lesions and risk of all-cause and cardiovascular mortality in people treated with long-term haemodialysis: The ORAL-D multinational cohort study.

Background: Chronic kidney disease is a risk factor for oral diseases, which may be associated with premature death. We evaluated the risk of all-cause and cardiovascular mortality associated with oral mucosal lesions in adults with kidney failure treated with long-term haemodialysis.

Methods: Oral mucosal lesions (herpes, ulceration, neoformation, white lesion, red lesion, oral candidiasis, geographical tongue, petechial lesions, and fissured tongue) were evaluated within the Oral Diseases in Haemodialysis (ORAL-D) study, a multinational cohort study of 4726 haemodialysis adults.

Associations of Cognitive Function and Education Level With All-Cause Mortality in Adults on Hemodialysis: Findings From the COGNITIVE-HD Study.

Rationale & Objective: In the general population, cognitive impairment is associated with increased mortality, and higher levels of education are associated with lower risks for cognitive impairment and mortality. These associations are not well studied in patients receiving long-term hemodialysis and were the focus of the current investigation.

Study Design: Prospective cohort study.

Increased uptake of oxLDL does not exert lipotoxic effects in insulin-secreting cells.

Modified lipoproteins can negatively affect beta cell function and survival. However, the mechanisms behind interactions of modified lipoproteins with beta cells - and in particular, relationships to increased uptake - are only partly clarified. By over-expressing the scavenger receptor CD36 (Tet-on), we increased the uptake of fluorescent low-density modified lipoprotein (oxLDL) into insulin-secreting INS-1 cells.

Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells.

Type 2 diabetes (T2D) develops after years of prediabetes during which high glucose (glucotoxicity) impairs insulin secretion. We report that the ATP-conducting mitochondrial outer membrane voltage-dependent anion channel-1 (VDAC1) is upregulated in islets from T2D and non-diabetic organ donors under glucotoxic conditions. This is caused by a glucotoxicity-induced transcriptional program, triggered during years of prediabetes with suboptimal blood glucose control.

Silencing of the FTO gene inhibits insulin secretion: An in vitro study using GRINCH cells.

Expression of fat mass and obesity-associated gene (FTO) and ADP-ribosylation factor-like 15 (ARL15) in human islets is inversely correlated with HbA. However, their impact on insulin secretion is still ambiguous. Here in, we investigated the role of FTO and ARL15 using GRINCH (Glucose-Responsive Insulin-secreting C-peptide-modified Human proinsulin) clonal rat β-cells.

The Association of Mediterranean and DASH Diets with Mortality in Adults on Hemodialysis: The DIET-HD Multinational Cohort Study.

Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets associate with lower cardiovascular and all-cause mortality in the general population, but the benefits for patients on hemodialysis are uncertain. Mediterranean and DASH diet scores were derived from the GALEN Food Frequency Questionnaire within the DIET-HD Study, a multinational cohort study of 9757 adults on hemodialysis. We conducted adjusted Cox regression analyses clustered by country to evaluate the association between diet score tertiles and all-cause and cardiovascular mortality (the lowest tertile was the reference category).

Dietary n-3 polyunsaturated fatty acid intake and all-cause and cardiovascular mortality in adults on hemodialysis: The DIET-HD multinational cohort study.

Background & Aims: Patients on hemodialysis suffer from high risk of premature death, which is largely attributed to cardiovascular disease, but interventions targeting traditional cardiovascular risk factors have made little or no difference. Long chain n-3 polyunsaturated fatty acids (n-3 PUFA) are putative candidates to reduce cardiovascular disease. Diets rich in n-3 PUFA are recommended in the general population, although their role in the hemodialysis setting is uncertain.

Glutamine-Elicited Secretion of Glucagon-Like Peptide 1 Is Governed by an Activated Glutamate Dehydrogenase.

Glucagon-like peptide 1 (GLP-1), secreted from intestinal L cells, glucose dependently stimulates insulin secretion from β-cells. This glucose dependence prevents hypoglycemia, rendering GLP-1 analogs a useful and safe treatment modality in type 2 diabetes. Although the amino acid glutamine is a potent elicitor of GLP-1 secretion, the responsible mechanism remains unclear.

Prevalence and patterns of cognitive impairment in adult hemodialysis patients: the COGNITIVE-HD study.

Background: Mounting evidence indicates an increased risk of cognitive impairment in adults with end-stage kidney disease on dialysis, but the extent and pattern of deficits across the spectrum of cognitive domains are uncertain.

Methods: We conducted a cross-sectional study of 676 adult hemodialysis patients from 20 centers in Italy, aiming to evaluate the prevalence and patterns of cognitive impairment across five domains of learning and memory, complex attention, executive function, language and perceptual-motor function. We assessed cognitive function using a neuropsychological battery of 10 tests and calculated test and domain z-scores using population norms (age or age/education).