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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free fatty acids (FFAs) play important physiological roles in many tissues as an energy source and as signaling molecules in various cellular processes. Elevated levels of circulating FFAs are associated with obesity, dyslipidemia, and diabetes. Here we show that GPR84, a previously orphan G protein-coupled receptor, functions as a receptor for medium-chain FFAs with carbon chain lengths of 9-14. Medium-chain FFAs elicit calcium mobilization, inhibit 3',5'-cyclic AMP production, and stimulate [35S]guanosine 5'-O-(3-thiotriphosphate) binding in a GPR84-dependent manner. The activation of GPR84 by medium-chain FFAs couples primarily to a pertussis toxin-sensitive G(i/o) pathway. In addition, we show that GPR84 is selectively expressed in leukocytes and markedly induced in monocytes/macrophages upon activation by lipopolysaccharide. Furthermore, we demonstrate that medium-chain FFAs amplify lipopolysaccharide-stimulated production of the proinflammatory cytokine interleukin-12 p40 through GPR84. Our results indicate a role for GPR84 in directly linking fatty acid metabolism to immunological regulation.
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PMID:Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. 1696 19

The efficacy, the ability to confer protection against a target disease and the safety of a vaccine are assessed in great detail before licensure. However, inherent limitations in the prelicensure assessment necessitate continued epidemiological evaluations of efficacy and safety issues after the introduction of vaccines into use. In Denmark, the opportunities available for epidemiological research are unique. In 2001, an initiative was undertaken to take advantage of these opportunities to study the postlicensure epidemiology of childhood vaccination with respect to effectiveness and safety. First, we describe the unique opportunities for postlicensure research in Denmark with respect to the data sources available and the epidemiological and statistical methods used. We then describe a number of recent postlicensure studies of effectiveness and safety that took advantage of these opportunities. Specifically, studies on the effectiveness of Haemophilus influenzae type b vaccination, the effectiveness of pertussis vaccination, the impact of a preschool pertussis booster on infant pertussis, measles-mumps-rubella vaccine and autism, thimerosal-containing vaccine and autism, measles-mumps-rubella vaccine and febrile seizures, childhood vaccination and Type 1 diabetes, and childhood vaccination and nontargeted infectious disease are discussed.
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PMID:Postlicensure epidemiology of childhood vaccination: the Danish experience. 1718 38

Morbidity and mortality due to vaccine-preventable diseases are high among persons with underlying medical conditions. Thus, inactivated influenza and pneumococcal polysaccharide vaccines are recommended for individuals with cardiac disease, diabetes mellitus, chronic obstructive pulmonary disease, immunosuppression, and other chronic illnesses. Inactivated influenza vaccine is recommended for pregnant women and for persons with asthma and neuromuscular disease. Palivizumab, a respiratory syncytial virus immunoglobulin preparation, is recommended for certain infants with prematurity and chronic lung disease. Health care workers are at high risk for acquiring and transmitting hepatitis B, pertussis, measles, varicella, and influenza; hence, vaccination against these diseases is recommended. A signed declination is recommended for health care workers who refuse influenza vaccination.
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PMID:Vaccines for persons at high risk, 2007. 1727 Jan 9

In the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), which was conducted from 2003 to 2006, data on acute/infectious and chronic diseases were collected from a population-based sample of 17,641 subjects aged 0 to 17 years. The annual prevalence rates among acute diseases vary widely. Children and adolescents are most frequently affected by acute (infectious) respiratory conditions. 88.5 % of the surveyed children and adolescents experienced at least one episode of common cold within the last 12 months. Among the other acute respiratory infections, bronchitis and tonsillitis were the most frequently encountered conditions with 19.9 % and 18.5 %, respectively. The 12-month prevalence of otitis media and pseudocroup was 11 % and 6.6 %, respectively. 1.5 % of the children and adolescents experienced an episode of pneumonia. Apart from respiratory infections, gastrointestinal infections were very frequently stated as reasons for acute illness. Furthermore, 12.8 % of the children and adolescents experienced a herpetic infection, 7.8 % a conjunctivitis and 4.8 % a urinary tract infection. Lifetime prevalence rates of infectious diseases were as follows: pertussis 8.7 %, measles 7.4 %, mumps 4.0 %, rubella 8.5 %, varicella 70.6 %, scarlet fever 23.5 %. The various chronic somatic diseases in children and adolescents had different lifetime prevalence rates. Most frequently, children and adolescents were affected by obstructive bronchitis (13.3 %), neurodermatitis/atopic eczema (13.2 %) and hay fever (10.7 %). Scoliosis and asthma had been diagnosed by a doctor in 5.2 % and 4.7 % of subjects aged 0-17 years, respectively. The lifetime prevalence rates of the remaining diseases varied between 0.14 % for diabetes mellitus and 3.6 % for convulsions/epileptic fits. For the first time ever, these survey results provide nationwide representative information on the prevalence rates of acute/infectious and chronic diseases in children and adolescents which is based on a population-representative sample.
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PMID:[Prevalence of somatic diseases in German children and adolescents. Results of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS)]. 1751 53

Ghrelin reportedly serves as a physiological regulator of insulin release. This study aimed to explore signaling mechanisms for insulinostatic ghrelin action in islet beta-cells, with special attention to heterotrimeric GTP-binding proteins and K(+) channels. Plasma insulin and growth hormone (GH) concentrations in rats were measured by enzyme-linked immunosorbent assay (ELISA). Islets were isolated from rats, ghrelin-knockout (Ghr-KO) mice, and wild-type mice by collagenase digestion, and insulin release was determined by ELISA. In rat single beta-cells, cytosolic Ca(2+) concentration ([Ca(2+)](i)) was measured by fura-2 microfluorometry, and membrane potentials and whole cell currents by patch-clamp technique. In rats, systemic ghrelin administration decreased plasma insulin concentrations, and this effect was blocked by treatment with pertussis toxin (PTX), whereas stimulation of GH release remained unaffected. In rat islets, ghrelin receptor antagonist increased and exogenous ghrelin suppressed glucose-induced insulin release in a PTX-sensitive manner. Glucose-induced insulin release from islets was greater in Ghr-KO than wild-type mice, and this enhanced secretion was blunted with PTX. Ghrelin PTX sensitively increased voltage-dependent K(+) (Kv) currents without affecting ATP-sensitive K(+) channels in rat beta-cells. In the presence of Kv channel blockers, ghrelin failed to suppress insulin release. Ghrelin attenuated glucose-induced action potentials and [Ca(2+)](i) increases in beta-cells. Suppressions of [Ca(2+)](i) increase and insulin release by ghrelin were blunted in beta-cells treated with PTX and with antisense oligonucleotide specific for G-protein Galpha(i2)-subunit. Ghrelin attenuates glucose-induced insulin release via PTX-sensitive Galpha(i2)-mediated activation of Kv channels and suppression of [Ca(2+)](i) in beta-cells, representing the unique signaling of ghrelin distinct from that for GH release.
Diabetes 2007 Sep
PMID:Ghrelin uses Galphai2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet beta-cells: novel signal transduction of ghrelin. 1757 83

Melatonin influences insulin secretion both in vivo and in vitro. (i) The effects are MT(1)-and MT(2)-receptor-mediated. (ii) They are specific, high-affinity, pertussis-toxin-sensitive, G(i)-protein-coupled, leading to inhibition of the cAMP-pathway and decrease of insulin release. [Correction added after online publication 4 December 2007: in the preceding sentence, 'increase of insulin release' was changed to 'decrease of insulin release'.] Furthermore, melatonin inhibits the cGMP-pathway, possibly mediated by MT(2) receptors. In this way, melatonin likely inhibits insulin release. A third system, the IP(3)-pathway, is mediated by G(q)-proteins, phospholipase C and IP(3), which mobilize Ca(2+) from intracellular stores, with a resultant increase in insulin. (iii) Insulin secretion in vivo, as well as from isolated islets, exhibits a circadian rhythm. This rhythm, which is apparently generated within the islets, is influenced by melatonin, which induces a phase shift in insulin secretion. (iv) Observation of the circadian expression of clock genes in the pancreas could possibly be an indication of the generation of circadian rhythms in the pancreatic islets themselves. (v) Melatonin influences diabetes and associated metabolic disturbances. The diabetogens, alloxan and streptozotocin, lead to selective destruction of beta-cells through their accumulation in these cells, where they induce the generation of ROS. Beta-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. Results suggest that melatonin in pharmacological doses provides protection against ROS. (vi) Finally, melatonin levels in plasma, as well as the arylalkylamine-N-acetyltransferase (AANAT) activity, are lower in diabetic than in nondiabetic rats and humans. In contrast, in the pineal gland, the AANAT mRNA is increased and the insulin receptor mRNA is decreased, which indicates a close interrelationship between insulin and melatonin.
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PMID:Melatonin, endocrine pancreas and diabetes. 1807 45

It is well-documented that melatonin influences insulin secretion. The effects are mediated by specific, high-affinity, pertussis-toxin-sensitive, G protein-coupled membrane receptors (MT(1) as well MT(2)), which are present in both the pancreatic tissue and islets of rats and humans, as well as in rat insulinoma cells (INS1). Via the Gi-protein-adenylatecyclase-3',5'-cyclic adenosine monophosphate (cAMP) and, possibly, the guanylatecyclase-cGMP pathways, melatonin decreases insulin secretion, whereas, by activating the Gq-protein-phospholipase C-IP(3) pathway, it has the opposite effect. For further analysis of the interactions between melatonin and insulin, diabetic rats were investigated with respect to melatonin synthesis in the pineal gland and plasma insulin levels. In this context, recent investigations have proven that type 2 diabetic rats and humans display decreased melatonin levels, whereas type 1 diabetic IDDM rats or those with diabetes induced by streptozotocin (STZ) of the present study show increased plasma melatonin levels and elevated AA-NAT-mRNA. Furthermore, the mRNA of pineal insulin receptors and beta1-adrenoceptors, including the clock genes Per1 and Bmal1 and the clock-controlled output gene Dbp, increases in both young and middle-aged STZ rats. The results therefore indicate that the decreased insulin levels in STZ-induced type 1 diabetes are associated with higher melatonin plasma levels. In good agreement with earlier investigations, it was shown that the elevated insulin levels observed in type 2 diabetes, are associated with decreased melatonin levels. The results thus prove that a melatonin-insulin antagonism exists. Astonishingly, notwithstanding the drastic metabolic disturbances in STZ-diabetic rats, the diurnal rhythms of the parameters investigated are maintained.
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PMID:Increased melatonin synthesis in pineal glands of rats in streptozotocin induced type 1 diabetes. 1862 57

Type 1 diabetes (T1D) is considered to be a T-cell-mediated autoimmune disease in which genetic predisposition is affected by HLA class II alleles and polymorphisms in cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene. We tested the hypothesis whether these T1D-related gene polymorphisms modulate cytokine response and thus contribute to the development of autoimmunity. The study includes 67 non-diabetic children, typed for HLA class II alleles and CTLA-4 polymorphisms (+49A/G, CT60A/G, CTBC217_1C/T). We measured cytokine secretion of peripheral blood mononuclear cells after stimulation with tetanus toxoid (TT), polio virus, coxsackie virus B4, pertussis toxin (PT) and phytohemagglutinin (PHA). We saw higher IL-13 response to TT in individuals with DR3-DQ2 haplotype (P = 0.002). HLA class II protective haplotype, DR2-DQ6, showed association with increased production of IFN-gamma (P < 0.001) and IL-2 (P = 0.005) in response to polio virus. In children with the autoimmunity-related homozygous genotypes CTLA-4 +49G/G, CT60G/G and CTBC217_1T/T, we found enhanced PT- and PHA-induced IFN-gamma production (P < 0.05). The cytokine responses to studied antigens were weakly modified by HLA class II risk haplotypes, and children with T1D-associated HLA risk haplotypes are not specifically inclined to develop an immune response in general. Higher IFN-gamma and IL-2 response to enterovirus in children with HLA class II protective haplotype DR2-DQ6 could be of importance in the protection from T1D-associated enterovirus infections. All autoimmunity related CTLA-4 polymorphisms were associated with enhanced IFN-gamma. This suggests impaired downregulation of cellular immunity by these CTLA-4 polymorphisms.
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PMID:Effect of HLA genotype or CTLA-4 polymorphism on cytokine response in healthy children. 1878 61

Abscisic acid (ABA) is a plant stress hormone recently identified as an endogenous pro-inflammatory cytokine in human granulocytes. Because paracrine signaling between pancreatic beta cells and inflammatory cells is increasingly recognized as a pathogenetic mechanism in the metabolic syndrome and type II diabetes, we investigated the effect of ABA on insulin secretion. Nanomolar ABA increases glucose-stimulated insulin secretion from RIN-m and INS-1 cells and from murine and human pancreatic islets. The signaling cascade triggered by ABA in insulin-releasing cells sequentially involves a pertussis toxin-sensitive G protein, cAMP overproduction, protein kinase A-mediated activation of the ADP-ribosyl cyclase CD38, and cyclic ADP-ribose overproduction. ABA is rapidly produced and released from human islets, RIN-m, and INS-1 cells stimulated with high glucose concentrations. In conclusion, ABA is an endogenous stimulator of insulin secretion in human and murine pancreatic beta cells. Autocrine release of ABA by glucose-stimulated pancreatic beta cells, and the paracrine production of the hormone by activated granulocytes and monocytes suggest that ABA may be involved in the physiology of insulin release as well as in its dysregulation under conditions of inflammation.
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PMID:Abscisic acid is an endogenous stimulator of insulin release from human pancreatic islets with cyclic ADP ribose as second messenger. 1878 81

The crucial pathology underlying progressive chronic kidney disease in diabetes is tubulointerstitial fibrosis. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by maladaptive transforming growth factor-beta1 (TGF-beta1) signaling. Novel signaling roles for C-peptide have recently been discovered with evidence emerging that C-peptide may mitigate microvascular complications of diabetes. We studied the potential for C-peptide to interrupt injurious TGF-beta1 signaling pathways and thus block development of EMT in HK2 human kidney proximal tubular cells. Cells were incubated with TGF-beta1 either alone or with C-peptide in low or high glucose. Changes in cell morphology, TGF-beta1 receptor expression, vimentin, E-cadherin, and phosphorylated Smads were assessed. Luciferase reporters were used to assess Smad activity. The cytoskeleton was visualized by TRITC-phalloidin staining. The typical TGF-beta1-stimulated, EMT-associated morphological alterations of proximal tubular cells, including increased vimentin expression, decreased E-cadherin expression, and cytoskeletal rearrangements, were prevented by C-peptide treatment. C-peptide also blocked TGF-beta1-induced upregulation of expression of both type I and type II TGF-beta1 receptors and attenuated TGF-beta1-mediated Smad phosphorylation and Smad transcriptional activity. These effects of C-peptide were inhibited by pertussis toxin. The results demonstrate that C-peptide almost completely reversed the morphological changes in PT cells induced by TGF-beta1 and suggest a role or C-peptide as a renoprotective agent in diabetic nephropathy.
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PMID:C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy. 1909 88


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