Diabetes causes significant increases in bladder weight but the natural history and underlying mechanisms are not known. In this study, we observed the temporal changes of detrusor muscle cells (DMC) and the calcineurin (Cn) and Akt expressions in detrusor muscle in the diabetic rat. Male Sprague-Dawley rats were divided into ...

The female gender reduces the risk, but succumbs more to cardiovascular disease. The hypothesis that short-term (8weeks) Streptozotocin-induced diabetes could produce greater female than male vascular tissue reactivity and the mechanistic basis were explored. Aortic ring responses to Phenylephrine were examined in age- and sex-matched normoglycaemic/diabetic rats. The normoglycaemic male ...

ABSTRACT: BACKGROUND: A suboptimal intrauterine environment may have a detrimental effect on gonadal development and thereby increases the risk for reproductive disorders and infertility in adult life. Here, we used uncontrolled maternal diabetes as a model to provoke pre- and perinatal growth restriction and evaluate the sexual development of rat ...

Krebs A, Schmidt-Trucksäss A, Doerfer J, Grulich-Henn J, Holder M, Hecker W, Krebs K, Barth M, Schwab KO. Cardiovascular risk in pediatric type 1 diabetes: sex-specific intima-media thickening verified by automatic contour identification and analyzing systems. Objectives: To improve screening and quantification of subclinical atherosclerosis in children and adolescents with ...

Our recent observations have demonstrated that gonadectomy in female, but not in male diabetic animals, exert protection in the peripheral nervous system and that these effects were associated with an increase in the levels of dehydroepiandrosterone (DHEA) in the female sciatic nerve [Pesaresi M, Giatti S, Cavaletti G, Abbiati F, ...

ABSTRACT: BACKGROUND: Diabetes mellitus is a chronic disease that can result in various medical, psychological and sexual dysfunctions (SD) if not properly managed. SD in men is a common under-appreciated complication of diabetes. This study assessed the prevalence and determinants of SD among diabetic patients in Tema, Greater Accra Region ...

Traditionally the role of sexual steroid hormones was focused primarily on reproductive organs: the breast, female reproductive tract (uterus, mammary gland, and ovary), and male reproductive tract (testes, epididymis and prostate), however our current understanding of tissue-specific effects of sex steroids has elucidated new aspects in its functionality. Recent data ...

MafA is a pancreatic transcriptional factor that controls β-cell-specific transcription of the insulin gene. However, the role of MafA in the regulation of pancreatic transdifferentiation and reprogramming in human stem cells is still unclear. In this study, we investigate the role of MafA in placenta-derived multipotent stem cells (PDMSCs) that ...

To examine changes in insulin sensitivity (SI), compensatory acute insulin response (AIR), and β-cell function/disposition index (DI) across puberty in overweight Latino boys and girls. Latino children (n = 253) were followed annually for up to 5 years. Longitudinal modeling was used to examine changes in SI, AIR, DI, and ...

A decrease in peak early diastolic filling velocity in postmenopausal women implies a sex hormone-related diastolic dysfunction. The regulatory effect of female sex hormones on cardiac distensibility therefore was evaluated in ovariectomized rat by determining the sarcomere length-passive tension relationship of ventricular skinned fiber preparations. Diabetes also was induced in ...

Calcineurin is an important signalling protein that regulates a number of molecular and cellular processes. Previously, we found that inhibition of calcineurin with cyclosporine reduced renal hypertrophy and blocked glomerular matrix expansion in the diabetic kidney. Isoforms of the catalytic subunit of calcineurin are reported to have tissue specific expression ...

Major depressive disorder (MDD) and type 2 diabetes have independent adverse effects on sexual functioning (SF). Bupropion (BU) reportedly has few sexual side effects, but its use in diabetes has not been studied. This article reports a planned secondary analysis of SF in 90 patients with type 2 diabetes treated ...

Common polymorphisms within the FTO (fat mass and obesity-associated) gene correlate with increased BMI (body mass index) and a rising risk of Type 2 diabetes. FTO is highly expressed in the brain but has also been detected in peripheral tissues, including the endocrine pancreas, although its function there is unclear. The ...

Abstract Aging is associated with a progressive decline of skeletal muscle function and insulin sensitivity. Sex differences in the insulin response to different physiological situations have been found, leading to the development of type 2 diabetes. The aim of this study was to investigate the changes in insulin sensitivity with ...

Physical inactivity and excessive food consumption play a major role in the etiology of obesity and type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the relationship of physical activity (PA) and eating behaviour with obesity and T2DM in citizens of Sofia, Bulgaria. A total ...

Hyperglycemia with severe reduction of plasma insulin level is frequently associated with acute ischemic heart disease. Since insulin is reported to be an anti thrombotic humoral factor, the mechanism of the impaired insulin synthesis was investigated. The plasma from the patients with acute myocardial infarction (AMI) was analyzed by SDS-polyacrylamide ...

Autophagy is an intracellular catabolic system, which enables cells to capture cytoplasmic components for degradation within lysosomes. Autophagy is involved in development, differentiation and tissue remodeling in various organisms, and is also implicated in certain diseases. Recent studies demonstrate that autophagy is necessary to maintain architecture and function of pancreatic ...

Introducing the calcineurin inhibitors cyclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) decrease survival rates. We sought, in a beta-cell culture model, to elucidate the pathogenic mechanisms behind NODAT and the relative contribution of the ...

Cdk5 activity has been implicated in brain development and the regulation of many neuronal processes. Recently, the expression of p35 and Cdk5 activity has been reported in pancreatic beta cells. Decreased Cdk5 activity enhanced glucose-stimulated insulin secretion. This suggests that Cdk5 may play an important role in the regulation of ...

Background: Several epidemiological studies revealed sex-specific differences during oral glucose tolerance tests (OGTTs), such as higher prevalence of glucose intolerance (i.e. increased glucose at the end of the OGTT) in females, which was not yet explained. Thus, we aimed to analyze sex-related distinctions on OGTT glucose metabolism, including gut absorption, ...

We sought to understand the mechanisms underlying glucose sensing in Drosophila melanogaster. We found that insulin-producing cells (IPCs) of adult Drosophila respond to glucose and glibenclamide with a burst-like pattern of activity. Under controlled conditions IPCs have a resting membrane potential of -62+/-4 mV. In response to glucose or glibenclamide, ...

Functional insulin receptor and its downstream effector PI3K (phosphoinositide 3-kinase) have been identified in pancreatic β-cells, but their involvement in the regulation of insulin secretion from β-cells remains unclear. In the present study, we investigated the physiological role of insulin and PI3K in glucose-induced biphasic insulin exocytosis in primary cultured ...

The pathogenesis of type 2 diabetes mellitus involves both peripheral insulin resistance and dysfunctional insulin secretion from the pancreatic β cell. Currently, there is intense research focus on delineating the etiologies of pancreatic β cell dysfunction in type 2 diabetes. However, there remains an unmet clinical need to establish therapeutic ...

Electrical activity in pancreatic β-cells plays a pivotal role in glucose-stimulated insulin secretion by coupling metabolism to calcium-triggered exocytosis. Mathematical models based on rodent data have helped in understanding the mechanisms underlying the electrophysiological patterns observed in laboratory animals. However, human β-cells differ in several aspects, and in particular in ...

The metabolic pathways that are involved in regulating insulin secretion from pancreatic β-cells are still incompletely understood. One potential regulator of the metabolic phenotype of β-cells is the transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT)/hypoxia-inducible factor (HIF)-1β. ARNT/HIF-1β levels are profoundly reduced in islets obtained from type 2 diabetic ...

Chronic hyperglycemia is a hallmark of type 2 diabetes and can contribute to progressive beta cell dysfunction and death. The aim of the present study was to identify pathways mediating high glucose-induced beta cell demise by a proteomic approach. INS-1E cells were exposed to 25 mM glucose for a sustained ...

Type 1 diabetes is considered non-reversible at end-stage disease when there is no measurable insulin production. However, there are indications that insulin-producing beta cells could be present or return if autoimmunity could be controlled. We therefore sought to determine whether immunosuppression therapy can reinstate beta cell function in patients with ...

To review available data on preservation and potential improvement of beta-cell function in patients with type 2 diabetes mellitus (T2DM) with use of currently available strategies and agents. Using key words, we performed a MEDLINE search of the relevant literature published through 2009 regarding the effects of available agents on ...

Betacellulin (BTC), a ligand of the epidermal growth factor receptor, has been shown to promote growth and differentiation of pancreatic β-cells and to improve glucose metabolism in experimental diabetic rodent models. Mesenchymal stem cells (MSCs) have been already proved to be multipotent. Recent work has attributed to rat and human ...

Pancreatic islets contain low activities of catalase, selenium-dependent glutathione peroxidase 1 (GPX1), and Cu,Zn-superoxide dismutase 1 (SOD1). Thus, enhancing expression of these enzymes in islets has been unquestionably favored. However, such an attempt has produced variable metabolic outcomes. While β cell-specific overexpression of Sod1 enhanced mouse resistance to streptozotocin-induced diabetes, ...

Diabetes is now generally accepted as a crucial event in the process of pancreatic cancer (PaC). However, molecular mechanisms underlying the relationship between diabetes and PaC are not fully understood. Regenerating gene (REG) Ialpha is a growth factor affecting pancreatic islet beta cells, and it has been shown to be ...

BACE1 (β-site amyloidogenic cleavage of precursor protein-cleaving enzyme 1) is a β-secretase protein that plays a central role in the production of the β-amyloid peptide in the brain and is thought to be involved in the Alzheimer's pathogenesis. In type 2 diabetes, amyloid deposition within the pancreatic islets is a ...

A few studies have reported the existence of depletion of synaptic vesicles, and changes in neurotransmitter release and in the content of exocytotic proteins in the hippocampus of diabetic rats. Recently, we found that diabetes alters the levels of synaptic proteins in hippocampal nerve terminals. Hyperglycemia is considered the main ...

Mutations in pancreatic duodenal homeobox (PDX1) are linked to human type 2 diabetes and maturity-onset diabetes of the young type 4. Consistent with this, Pdx1-haploinsufficient mice develop diabetes. Both apoptosis and necrosis of β cells are mechanistically implicated in diabetes in these mice, but a molecular link between Pdx1 and ...

We determined whether hyperglycaemia stimulates human beta cell replication in vivo in an islet transplant model Human islets were transplanted into streptozotocin-induced diabetic NOD-severe combined immunodeficiency mice. Blood glucose was measured serially during a 2 week graft revascularisation period. Engrafted mice were then catheterised in the femoral artery and vein, and ...

It is not fully understood how the expression level of autoantigens in beta cells impacts autoimmune diabetes (T1D) development. Earlier studies using ovalbumin and also insulin had shown that secreted antigens could enhance diabetes development through facilitated presentation by antigen presenting cells. Here we sought to determine how the expression ...

Loss of circadian clocks from all tissues causes defective glucose homeostasis as well as loss of feeding and activity rhythms. Little is known about peripheral tissue clocks, so we tested the hypothesis that an intrinsic circadian clock of the pancreas is important for glucose homeostasis. We monitored real-time bioluminescence of ...

Studies evaluating the effects of oral antidiabetic drugs (OADs) on beta-cell function in type 2 diabetes mellitus (T2DM) are confounded by an inability to establish the actual baseline degree of beta-cell dysfunction, independent of the deleterious effects of hyperglycaemia (glucotoxicity). Because intensive insulin therapy (IIT) can induce normoglycaemia, we reasoned ...

Quercetin lowers plasma glucose, normalizes glucose tolerance tests and preserves pancreatic β-cell integrity in diabetic rats. However, its mechanism of action has never been explored in insulin-secreting β-cells. Using the INS-1 β-cell line, the effects of quercetin were determined on glucose- or glibenclamide-induced insulin secretion and on β-cell dysfunctions induced ...

Insulin resistance results, in part, from impaired insulin signaling in insulin target tissues. Consequently, increased levels of insulin are necessary to control plasma glucose levels. The effects of elevated insulin levels on pancreatic beta (β) cell function, however, are unclear. In this study, we investigated the possibility that insulin may ...

Reduced telomere length and impaired telomerase activity have been linked to several diseases associated with senescence and aging. However, a causal link to metabolic disorders and in particular diabetes mellitus is pending. We here show that young adult mice which are deficient for the Terc subunit of telomerase exhibit impaired ...

Post-transplant diabetes mellitus (PTDM) is a serious complication after transplantation. The complex clinical situation makes it difficult to distinct influence of the single factors. To define impact of calcineurin inhibitor therapy on the PTDM after transplantation an experimental study analyzing the impact of different tacrolimus - dosages on the pancreatic ...

α-Synuclein has been studied in numerous cell types often associated with secretory processes. In pancreatic β-cells, α-synuclein might therefore play a similar role by interacting with organelles involved in insulin secretion. We tested for α-synuclein localizing to insulin-secretory granules and characterized its role in glucose-stimulated insulin secretion. Immunohistochemistry and fluorescent ...

Studies have demonstrated that mesenchymal stem-like cells can be isolated from endometrium. However, the potential of endometrial-derived stem cells to differentiate into insulin-positive cells and functionally secrete insulin remains undetermined. We isolated endometrial mesenchymal stem-like cells (EMSCs) from human endometrial tissue from six donors. The insulin-secreting function of EMSCs was ...

Chronic ethanol consumption is known as an independent risk factor for type 2 diabetes, which is characterized by impaired glucose homeostasis and insulin resistance; however, there is a great deal of controversy concerning the relationships between alcohol consumption and the development of type 2 diabetes. We investigated the effects of ...

PERK (EIF2AK3) was originally discovered as a major component of the unfolded protein response (UPR). PERK deficiency results in permanent neonatal diabetes, which was initially thought to be caused by a failure to regulate ER stress in insulin-secreting beta cells, culminating in beta cell death. However, subsequent studies found that ...

The G protein-coupled receptor 119 (GPR119) is highly expressed in pancreatic β-cells. On activation, this receptor enhances the effect of glucose-stimulated insulin secretion (GSIS) via the elevation of intracellular cAMP concentrations. Although GPR119 agonists represent promising oral antidiabetic agents for the treatment of type 2 diabetes therapy, they suffer from ...

The aim of this study is to compare the utility of two positron emission tomography (PET) imaging ligands ((+)-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ) and the fluoropropyl analog ([(18)F]FP-(+)-DTBZ)) that target islet β-cell vesicular monoamine transporter type II to measure pancreatic β-cell mass (BCM). [(11)C]DTBZ or [(18)F]FP-(+)-DTBZ was injected, and serial PET images were ...

Weak pancreatic β-cell function is a cause of type 2 diabetes mellitus. Glucokinase regulates insulin secretion via phosphorylation of glucose. The present study focused on a system for the self-protection of pancreatic cell by expressing heat shock factor (HSF) and heat shock protein (HSP) to improve insulin secretion without inducing ...

The incidence of type 2 diabetes mellitus has markedly increased worldwide over the past decades. Pancreatic beta-cell dysfunction as well as central and peripheral insulin resistance appears to be elementary features in the pathophysiology of type 2 diabetes mellitus. Major environmental conditions predisposing to the development of type 2 diabetes ...