Diabetic Polyneuropathy: New Strategies to Target Sensory Neurons in Dorsal Root Ganglia.

Diabetic polyneuropathy (DPN) is the most common type of diabetic neuropathy, rendering a slowly progressive, symmetrical, and length-dependent dying-back axonopathy with preferential sensory involvement. Although the pathogenesis of DPN is complex, this review emphasizes the concept that hyperglycemia and metabolic stressors directly target sensory neurons in the dorsal root ganglia (DRG), leading to distal axonal degeneration. In this context, we discuss the role for DRG-targeting gene delivery, specifically oligonucleotide therapeutics for DPN.

Muscle sympathetic nerve activity during pregnancy: A systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to quantify the impact of healthy and complex pregnancy on muscle sympathetic nerve activity (MSNA) at rest, and in response to stress. Structured searches of electronic databases were performed until February 23, 2022. All study designs (except reviews) were included: population (pregnant individuals); exposures (healthy and complicated pregnancy with direct measures of MSNA); comparator (individuals who were not pregnant, or with uncomplicated pregnancy); and outcomes (MSNA, BP, and heart rate).

Cryopreservation and post-thaw characterization of dissociated human islet cells.

The objective of this study is to optimize the cryopreservation of dissociated islet cells and obtain functional cells that can be used in single-cell transcriptome studies on the pathology and treatment of diabetes. Using an iterative graded freezing approach we obtained viable cells after cooling in 10% dimethyl sulfoxide and 6% hydroxyethyl starch at 1°C/min to -40°C, storage in liquid nitrogen, rapid thaw, and removal of cryoprotectants by serial dilution. The expression of epithelial cell adhesion molecule declined immediately after thaw, but recovered after overnight incubation, while that of an endocrine cell marker (HPi2) remained high after cryopreservation.

TRPV1 channels as a newly identified target for vitamin D.

Vitamin D is known to elicit many biological effects in diverse tissue types and is thought to act almost exclusively upon its canonical receptor within the nucleus, leading to gene transcriptional changes and the subsequent cellular response. However, not all the observed effects of vitamin D can be attributed to this sole mechanism, and other cellular targets likely exist but remain to be identified. Our recent discovery that vitamin D is a partial agonist of the Transient Receptor Potential Vanilloid family 1 (TRPV1) channel may provide new insights as to how this important vitamin exerts its biological effects either independently or in addition to the nuclear vitamin D receptor.

Effects of Exercise on Mild-to-Moderate Depressive Symptoms in the Postpartum Period: A Meta-analysis.

Objective: To examine the influence of exercise on depressive symptoms and the prevalence of depression in the postpartum period.

Data Sources: A structured search of MEDLINE, EMBASE, CINAHL, Sport Discus, Ovid's All EBM Reviews, and ClinicalTrials.gov databases was performed with dates from the beginning of the databases until June 16, 2016.

Improved Glucose Homeostasis in Obese Mice Treated With Resveratrol Is Associated With Alterations in the Gut Microbiome.

Oral administration of resveratrol is able to improve glucose homeostasis in obese individuals. Herein we show that resveratrol ingestion produces taxonomic and predicted functional changes in the gut microbiome of obese mice. In particular, changes in the gut microbiome were characterized by a decreased relative abundance of Turicibacteraceae, Moryella, Lachnospiraceae, and Akkermansia and an increased relative abundance of Bacteroides and Parabacteroides Moreover, fecal transplantation from healthy resveratrol-fed donor mice is sufficient to improve glucose homeostasis in obese mice, suggesting that the resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol.

PI3 kinases p110α and PI3K-C2β negatively regulate cAMP via PDE3/8 to control insulin secretion in mouse and human islets.

Objectives: Phosphatidylinositol-3-OH kinase (PI3K) signalling in the endocrine pancreas contributes to glycaemic control. However, the mechanism by which PI3K modulates insulin secretion from the pancreatic beta cell is poorly understood. Thus, our objective was two-fold; to determine the signalling pathway by which acute PI3K inhibition enhances glucose-stimulated insulin secretion (GSIS) and to examine the role of this pathway in islets from type-2 diabetic (T2D) donors.

Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity.

Chronic intake of saturated free fatty acids is associated with diabetes and may contribute to the impairment of functional beta cell mass. Mitogen activated protein kinase 8 interacting protein 1 also called islet brain 1 (IB1) is a candidate gene for diabetes that is required for beta cell survival and glucose-induced insulin secretion (GSIS). In this study we investigated whether IB1 expression is required for preserving beta cell survival and function in response to palmitate.

Rp-cAMPS Prodrugs Reveal the cAMP Dependence of First-Phase Glucose-Stimulated Insulin Secretion.

cAMP-elevating agents such as the incretin hormone glucagon-like peptide-1 potentiate glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. However, a debate has existed since the 1970s concerning whether or not cAMP signaling is essential for glucose alone to stimulate insulin secretion. Here, we report that the first-phase kinetic component of GSIS is cAMP-dependent, as revealed through the use of a novel highly membrane permeable para-acetoxybenzyl (pAB) ester prodrug that is a bioactivatable derivative of the cAMP antagonist adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS).

Insulin secretion induced by glucose-dependent insulinotropic polypeptide requires phosphatidylinositol 3-kinase γ in rodent and human β-cells.

PI3Kγ, a G-protein-coupled type 1B phosphoinositol 3-kinase, exhibits a basal glucose-independent activity in β-cells and can be activated by the glucose-dependent insulinotropic polypeptide (GIP). We therefore investigated the role of the PI3Kγ catalytic subunit (p110γ) in insulin secretion and β-cell exocytosis stimulated by GIP. We inhibited p110γ with AS604850 (1 μmol/liter) or knocked it down using an shRNA adenovirus or siRNA duplex in mouse and human islets and β-cells.

The transcultural diabetes nutrition algorithm: a canadian perspective.

The Transcultural Diabetes Nutrition Algorithm (tDNA) is a clinical tool designed to facilitate implementation of therapeutic lifestyle recommendations for people with or at risk for type 2 diabetes. Cultural adaptation of evidence-based clinical practice guidelines (CPG) recommendations is essential to address varied patient populations within and among diverse regions worldwide. The Canadian version of tDNA supports and targets behavioural changes to improve nutritional quality and to promote regular daily physical activity consistent with Canadian Diabetes Association CPG, as well as channelling the concomitant management of obesity, hypertension, dyslipidemia, and dysglycaemia in primary care.

Exercise lowers postprandial glucose but not fasting glucose in type 2 diabetes: a meta-analysis of studies using continuous glucose monitoring.

Exercise has repeatedly been shown to improve glycemic control as assessed by glycated hemoglobin. However, changes in glycated hemoglobin do not provide information regarding which aspects of glycemic control have been altered. The purpose of this systematic review was to examine the effect of exercise as assessed by continuous glucose monitoring systems (CGMS) in type 2 diabetes.

Timing of excessive pregnancy-related weight gain and offspring adiposity at birth.

Objective: To evaluate whether the timing of excessive maternal weight gain in a cohort of women following current guidelines for healthy living during pregnancy affects neonatal adiposity at birth.

Methods: One hundred seventy-two healthy women who were at least 18 years old with body mass indexes (BMIs) of at least 18.5 were recruited between 16 weeks and 20 weeks of gestation.

Functional plasticity of the human infant β-cell exocytotic phenotype.

Our understanding of adult human β-cells is advancing, but we know little about the function and plasticity of β-cells from infants. We therefore characterized islets and single islet cells from human infants after isolation and culture. Although islet morphology in pancreas biopsies was similar to that in adults, infant islets after isolation and 24-48 hours of culture had less insulin staining, content, and secretion.

G protein-coupled receptor (GPR)40-dependent potentiation of insulin secretion in mouse islets is mediated by protein kinase D1.

Aims/hypothesis: Activation of the G protein-coupled receptor (GPR)40 by long-chain fatty acids potentiates glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells, and GPR40 agonists are in clinical development for type 2 diabetes therapy. GPR40 couples to the G protein subunit Gα(q/11) but the signalling cascade activated downstream is unknown. This study aimed to determine the mechanisms of GPR40-dependent potentiation of GSIS by fatty acids.

Insulin granule recruitment and exocytosis is dependent on p110gamma in insulinoma and human beta-cells.

Objective: Phosphatidylinositol 3-OH kinase (PI3K) has a long-recognized role in beta-cell mass regulation and gene transcription and is implicated in the modulation of insulin secretion. The role of nontyrosine kinase receptor-activated PI3K isoforms is largely unexplored. We therefore investigated the role of the G-protein-coupled PI3Kgamma and its catalytic subunit p110gamma in the regulation of insulin granule recruitment and exocytosis.