Aim  Screening for peripheral arterial disease, a complication among patients with diabetes, is performed by periodic assessment of ankle-brachial index. We aimed to study the degree of ankle-brachial index change over time and factors associated with significant change. Method  We assessed difference between two ankle-brachial index measurements over time in ...

AIM: As optimizing glucose control in critically ill patients remains a challenge for intensive-care physicians, this study aimed to determine the accuracy of glucose measurements. METHODS: The accuracy of capillary and arterial blood glucose meter measurements was compared with central laboratory arterial glucose measurements; the factors associated with inaccurate measures ...

OBJECTIVETo investigate the effect of flexible intensive insulin therapy (FIIT) and an automated bolus calculator (ABC) in a Danish type 1 diabetes population treated with multiple daily injections. Furthermore, to test the feasibility of teaching FIIT in a 3-h structured course.RESEARCH DESIGN AND METHODSThe BolusCal Study was a 16-week randomized, ...

In pancreatic β-cells, the endoplasmic reticulum (ER) is the crucial site for insulin biosynthesis, as this is where the protein-folding machinery for secretory proteins is localized. Perturbations to ER function of the β-cell, such as those caused by high levels of free fatty acid and insulin resistance, can lead to ...

A low plasma level of HDL cholesterol is an atherosclerotic risk factor; however, emerging evidence suggests that low HDL levels might also contribute to the pathophysiology of type 2 diabetes mellitus (T2DM) through direct effects on plasma glucose. In the past decade, animal and clinical studies have uncovered a previously ...

The liver is a major insulin-responsive tissue responsible for glucose regulation. One important mechanism in this phenomenon is insulin-induced glycogen synthesis. Studies in our laboratory have shown that Protein Kinase Cs delta (PKCδ) and alpha (α) have important roles in insulin-induced glucose transport in skeletal muscle, and that their expression ...

Aims: In order to test the anti-diabetic efficacy of ibipinabant, this new cannabinoid receptor 1 (CB1) antagonist was compared with food-restriction-induced weight loss, rosiglitazone (4 mg/kg) and rimonabant (3 and 10 mg/kg), using parameters of glycemic control in male ZDF rats. Materials and Methods: Body weight, food and water intake, ...

Various complex mechanisms and their multifactorial pathways decisively provoke low-grade local and systemic inflammation in β-cells of pancreatic islets and peripheral tissues to induce β-cells' dysfunction and apoptosis, insulin resistance, and ultimately, overt type 2 diabetes mellitus (T2DM). Conventional antidiabetic agents are being less popular, as they have some potential ...

The mechanisms responsible for the accelerated atherosclerosis observed in type 2 diabetes are not fully understood. One of the earliest events in the development of atherosclerosis is endothelial dysfunction, namely, a reduction in nitric oxide (NO) synthesis or its bioavailability within the peri-endothelial environment, where it is responsible for maintenance ...

To examine whether the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a key regulator linking angiogenesis and metabolism, could enhance the engraftment and angiogenesis of mesenchymal stem cells (MSCs) in diabetic hindlimb ischemia, we engineered the overexpression of PGC-1α within MSCs using an adenoviral vector encoding green fluorescent protein and PGC-1α, and ...

INTRODUCTION: Although diabetic nephropathy is attributable to transforming growth factor-β1 (TGF-β1) overproduction in glomerular mesangial cells, the biological role of Wnt/β-catenin signaling in controlling high glucose-induced TGF-β1 has not yet been elucidated. METHODS: This study found that sustained Wnt/β-catenin signaling was required to protect glomerular mesangial cells from high glucose ...

INTRODUCTION: The objective is to investigate the influence of ghrelin administration on both the insulin secretion and the expression of ATP-sensitive K channels in islet. METHODS: Ghrelin and [D-Lys] growth hormone releasing peptide-6 were administered via intraperitoneal injection in Wistar rats at the doses 10 and 10 μmol/kg/d for 2 ...

Type 2 diabetes mellitus is characterized by insulin resistance and failure of pancreatic b-cells producing insulin. Autophagy plays a crucial role in cellular homeostasis through degradation and recycling of organelles such as mitochondria or ER. Here we discussed the role of b-cell autophagy in development of diabetes, based on our ...

BACKGROUND: Ileal transposition (IT) as one of the effective treatments for non-obese type 2 diabetes mellitus has been widely investigated. However, the mechanisms underlying profound improvements in glucose homeostasis are still uncertain. Our objective was to explore the myocardial insulin signal transduction and glucose disposal in non-obese type 2 diabetes ...

ABSTRACT: BACKGROUND: An impairment of cardiovascular function in streptozotocin (STZ)-diabetic rats has been mentioned within 5 days-to-3 months of induction. ATP-sensitive potassium (KATP) channels are expressed on cardiac sarcolemmal membranes. It is highly responsive to metabolic fluctuations and can have effects on cardiac contractility. The present study attempted to clarify ...

Insulin and insulin-like growth factor 1 (IGF-1) are evolutionarily conserved hormonal signalling molecules, which influence a wide array of physiological functions including metabolism, growth and development. Using genetic mouse studies, both insulin and IGF-1 have been shown to be anabolic agents in osteoblasts and bone development primarily through the activation ...

Islets isolated from cadaveric donor pancreas are functionally viable and can be transplanted in diabetic patients to reduce insulin requirements. This therapeutic approach is less efficient because a significant portion of functional islets is lost due to oxidative stress, inflammation, and hypoxia. Exendin-4, a glucagon-like peptide-1 receptor agonist, is known ...

Insulin signaling in osteoblasts contributes to whole body glucose homeostasis in the mouse and in humans by increasing the activity of osteocalcin. The osteoblast insulin signaling cascade is negatively regulated by ESP, a tyrosine phosphatase dephosphorylating the insulin receptor. Esp is one of many tyrosine phosphatases expressed in osteoblasts, and ...

OBJECTIVE: The association of hypovitaminosis D with type 2 diabetes is well recognized. Although hypovitaminosis D is associated with insulin resistance, there is much less information about its impact on β-cell function in humans. METHODS: We enrolled 150 healthy, glucose-tolerant subjects for the assessment of β-cell function (acute insulin response) ...

We report a two-photon turn-on probe (AS1) that can be excited by 780 nm femto-second pulses and visualize glucose uptake and the changes in the intracellular glucose concentration in live cells and tissue by two-photon microscopy.

The glucose transporter 4 (GLUT4) is responsible for glucose uptake in the skeletal muscle. Insulin-induced translocation of GLUT4 to the plasma membrane requires phosphatidylinositol (PI) 3-kinase activation-mediated generation of phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) and subsequent activation of Akt. Previous studies suggested that skeletal muscle and kidney enriched inositol polyphosphate phosphatase (SKIP) ...

Bone marrow (BM) holds a pool of stem and progenitor cells whose role is not limited to hematopoiesis. Indeed, growing evidences showed that BM-derived progenitors could contribute to various extents to cardiovascular homeostasis. Notably, diabetic patients experience an intrinsic defect of the progenitor pool, whereas some recent works point directly ...

Amino-acid starvation leads to an inhibition of cellular proliferation and the induction of programmed cell death (PCD) in the Drosophila ovary. Disruption of insulin signaling has been shown to inhibit the progression of oogenesis, but it is unclear whether this phenotype mimics starvation. Here, we investigate whether the insulin-mediated phosphoinositide ...

Diabetes during pregnancy causes neurodevelopmental and neurocognitive abnormalities in offspring. Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. We examined the effects of maternal diabetes on insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) expression in the developing ...

ABSTRACT The present study investigated the role of D-saccharic acid 1,4-lactone (DSL) in the spleeen tissue of alloxan (ALX) induced diabetic rats. Diabetes was induced in rats by injecting ALX (at a dose of 120 mg/kg body weight) intraperitoneally in sterile normal saline. Elevated levels of blood glucose, glycosylated Hb ...

Rates of diabetes are reaching epidemic levels. The key problem in both type 1 and type 2 diabetes is dysfunctional insulin signaling, either due to lack of production or due to impaired insulin sensitivity. A key feature of diabetic retinopathy in animal models is degenerate capillary formation. The goal of ...

AIMS/HYPOTHESIS: Glucokinase activators (GKAs) are currently being developed as new therapies for type 2 diabetes and have been shown to enhance beta cell survival and proliferation in vitro. Here, we report the effects of chronic GKA treatment on the development of hyperglycaemia and beta cell loss in the male Zucker ...

Vascular dysfunction is a common consequence of diabetes mellitus. Stable propagation of gene expression from cell to cell during development of diseases (like diabetes) is regulated by epigenetic mechanisms. These are heritable patterns of gene expression that cannot solely be explained by changes in the DNA sequence. Recent evidence shows ...

Diabetes mellitus is considered a cardiovascular disease owing to its prevalent association with cardiovascular morbidity and mortality. Cardiovascular events are not only more frequent but also complicated with more severe outcomes in diabetic patients as compared with non-diabetic patients. One mechanism accounting for this difference consists of the impairment of ...

GLP-1 based incretin therapy is becoming central to the treatment of Type-2 diabetes. Activation of incretin hormone receptors results in rapid elevation of cAMP followed by enhanced insulin secretion. However, the incretin effect may be significantly impaired in diabetes. The objective of this study is to investigate down-regulation of GLP-1 ...

AIMS: T-cadherin (T-cad) is a glycosylphosphatidylinositol-anchored cadherin family member. Experimental, clinical, and genomic studies suggest a role for T-cad in vascular disorders such as atherosclerosis and hypertension, which are associated with endothelial dysfunction and insulin resistance (InsRes). In endothelial cells (EC) T-cad and insulin activate similar signaling pathways (e.g. PI3-kinase/Akt/mTOR) ...

Acetylcholinesterase (AChE) expression is pivotal during apoptosis. Indeed, AChE inhibitors partially protect cells from apoptosis. Insulin-dependent diabetes mellitus (IDDM) is characterized in part by pancreatic β-cell apoptosis. Here, we investigated the role of AChE in the development of IDDM and analyzed protective effects of AChE inhibitors. Multiple low-dose streptozotocin (MLD-STZ) ...

ABSTRACT: BACKGROUND: Clevudine is a nucleoside analog reverse transcriptase inhibitor that exhibits potent antiviral activity against hepatitis B virus (HBV) without serious side effects. However, mitochondrial myopathy has been observed in patients with chronic HBV infection taking clevudine. Moreover, the development of diabetes was recently reported in patients receiving long-term ...

In this issue of Journal of Endocrinology, Dr Han and colleagues report a protective effect of the glutamate dehydrogenase-activator BCH under diabetes-like conditions that impair β-cell function in both a pancreatic β-cell line and in db/db mice. Based on these observations, the authors suggest that BCH could serve as novel ...

Body fat, insulin resistance and type2 diabetes are often linked together, but the molecular mechanisms that unify their association are poorly understood. Wnt signaling regulates adipogenesis and its altered activity has been implicated in the pathogenesis of type2 diabetes and metabolic syndrome. LRP6+/- mice on high fat diet were protected ...

PURPOSE OF REVIEW: It has been demonstrated that fatty acids (FAs) are physiological ligands of G-protein-coupled receptors (GPRs). Activation of the GPRs (40, 41, 43, 84, 119 and 120) by FAs or synthetic agonists modulates several responses. In this review, we discuss the current knowledge on the actions of FA-activated ...

Animal growth depends on nutritional intake during development. In many animals, nutritional status is uncoupled from moderation of adult stature after adult size is achieved. However, some long-lived animals continue to regulate adult size and fertility in a nutrition-dependent manner. For example, the regenerating flatworm Schmidtea mediterranea becomes smaller, or ...

Metabolic memory (MM) is the phenomenon whereby diabetes complications persist and progress after glycemic recovery is achieved. Here, we present data showing that MM is heritable and that the transmission correlates with hyperglycemia-induced DNA hypomethylation and aberrant gene expression. Streptozocin was used to induce hyperglycemia in adult zebrafish, and then, ...

BACKGROUND: Mammalian excision repair cross-complementing1 (ERCC1) and ERCC4 (a.k.a Xeroderma pigmentosum complementation group F, XPF) are nucleotide excision repair enzymes, which excise the 5' end of damaged DNA. ERCC1 and ERCC4 have an interactive relationship with Poly (ADP-Ribose) polymerase (PARP). We studied the role of ERCC1 and ERCC4 in glucose ...

Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we ...

Inflammation plays an important role in diabetes-induced retinal vascular leakage. The purpose of this study is to examine the role of endoplasmic reticulum (ER) stress and the signaling pathway of ER stress-induced activating transcription factor 4 (ATF4) in the regulation of Müller cell-derived inflammatory mediators in diabetic retinopathy. In diabetic ...

For some years now, reduced testosterone levels have been related to obesity, insulin resistance, type 2 diabetes, heart disease, benign prostatic hypertrophy and even prostate cancer - often considered guilty more by association, than actual cause - with little attention paid to the important role of increased intracellular oestrogen, in ...

Type 1 diabetes mellitus is caused by the autoimmune destruction of β cells within the islets. In recent years, innate immunity has been proposed to play a key role in this process. High-mobility group box 1 (HMGB1), an inflammatory trigger in a number of autoimmune diseases, activates proinflammatory responses following ...

The role of the cytokine interleukin-6 (IL-6) in metabolic homeostasis is the subject of conjecture. Recent work in Nature Medicine (Ellingsgaard et al., 2011) demonstrates that IL-6 released from skeletal muscle during exercise mediates crosstalk between insulin-sensitive tissues, intestinal L cells, and pancreatic islets to adapt to changes in insulin demand.

The hormone glucagon has long been dismissed as a minor contributor to metabolic disease. Here we propose that glucagon excess, rather than insulin deficiency, is the sine qua non of diabetes. We base this on the following evidence: (a) glucagon increases hepatic glucose and ketone production, catabolic features present in ...

Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of pancreatic beta cells. Recently, small cationic α-defensin molecules have been implicated in the pathogenesis of certain inflammatory and autoimmune diseases. The purpose of this study was to assess the α-defensin expression in patients with T1D and ...

Type I diabetes results from the autoimmune destruction of the insulin-secreting pancreatic β-cells, affecting many millions of people worldwide. The optimal treatment is to restore the endogenous supply of insulin either through the transplantation of pancreas or the transplantation of islets of langerhans or simply the β-cells. However, the donated ...

Placentomegaly, an abnormal increase in the size of the placenta, is commonly seen in human diabetic pregnancies and diabetic animal experimental models. Proper placental development depends on the proliferation and differentiation of trophoblasts. However, our knowledge about the mitotic regulators that play key roles in synchronizing these events is limited. ...

It is well known that sulphonylureas (SUs), commonly used in the treatment of type 2 diabetes mellitus, stimulate insulin secretion by closing ATP-sensitive K(+) (K(ATP) ) channels in pancreatic β-cells by binding to the SU receptor SUR1. SUs are now known also to activate cAMP sensor Epac2 (cAMP-GEFII) to Rap1 ...

Summary:  The last several years have seen breakthroughs in techniques to track the symbiont communities that normally colonize mammals (the microbiota) and in cataloguing the universe of the genes they carry (the microbiome). Applying these methods to human patients and corresponding murine models should allow us to decipher just how ...