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Background/objectives: The identification of brown/beige adipose tissue in adult humans has motivated the search for methods aimed at increasing its thermogenic activity as an approach to treat obesity. In rodents, the brown adipose tissue is under the control of sympathetic signals originating in the hypothalamus. However, the putative connection between the depots of brown/beige adipocytes and the hypothalamus in humans has never been explored. The objective of this study was to evaluate the response of the hypothalamus and brown/beige adipose tissue to cold stimulus in obese subjects undergoing body mass reduction following gastric bypass.Subjects/methods: We evaluated twelve obese, non-diabetic subjects undergoing Roux-in-Y gastric bypass and 12 lean controls. Obese subjects were evaluated before and approximately 8 months after gastric bypass. Lean subjects were evaluated only at admission. Subjects were evaluated for hypothalamic activity in response to cold by functional magnetic resonance, whereas brown/beige adipose tissue activity was evaluated using a (F 18) fluorodeoxyglucose positron emisson tomography/computed tomography scan and real-time PCR measurement of signature genes.Results: Body mass reduction resulted in a significant increase in brown/beige adipose tissue activity in response to cold; however, no change in cold-induced hypothalamic activity was observed after body mass reduction. No correlation was found between brown/beige adipose tissue activation and hypothalamus activity in obese subjects or in lean controls.Conclusions: In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance. [ABSTRACT FROM AUTHOR]

Objectives:Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown.Subjects:Adipose tissue autophagy was evaluated in mice and humans.Results:First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue.Conclusion:Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently. [ABSTRACT FROM AUTHOR]

Context:Recent studies have shown that xenin can act in the hypothalamus, reducing food intake through a leptin- and melanocortin system-independent mechanism.Objective:To evaluate the impact of body mass reduction on the blood and cerebrospinal fluid (CSF) levels of xenin.Design and setting:Thirteen obese patients (11 women) selected for roux-in-Y gastric bypass surgery were evaluated before and approximately 8 months after surgery. Xenin was determined in serum and CSF by radioimmunoassay.Results:As compared with lean subjects, obese patients have increased blood levels of xenin, which reduce after surgery. There are significant correlations between blood xenin and blood leptin and insulin levels. CSF concentration of xenin is ∼10-fold lower than blood levels, and is significantly higher in obese subjects as compared with lean ones, returning to normal levels after body mass reduction. There is a significant linear correlation between CSF and blood levels of xenin.Conclusion:Xenin is present in the human CSF in a concentration ∼10-fold lower than the blood. Both blood and CSF xenin are correlated with blood levels of important markers of adiposity, leptin and insulin. The levels of CSF xenin are linearly correlated with blood xenin, independently of patient body mass, suggesting that either its transport across the blood-brain barrier is not saturated in the concentration range detected in this study or that there is a coordinated release of xenin from the periphery and the CNS. [ABSTRACT FROM AUTHOR]

Aims/Hypothesis:Bariatric surgery is currently employed as an effective approach to treat class III obesity and class II obesity with co-morbidities. Unfortunately, the general anthropometric and metabolic outcomes of the surgery are not homogeneous, and defining the eligibility criteria that allow for a more precise prediction of the outcomes of this invasive procedure will refine the selection of patients. Here we tested the hypothesis that the Gly482Ser polymorphism of the ppargc1a gene would predict different outcomes following bariatric surgery.Methods:Fifty-five patients (26 Gly/Gly and 29 Gly/Ser+Ser/Ser) selected for the Roux-en-Y gastric bypass according to the National Institutes of Health Consensus Statement criteria were followed up for 1 year, monitoring their anthropometric, metabolic and inflammatory parameters.Results:Patients with the Gly482Ser polymorphism had significantly improved reductions in the waist/hip ratio, fasting blood glucose, C-reactive protein, blood leukocyte count, serum interleukin-6 and intima-media thickness of the carotid artery, as compared with Gly/Gly patients.Conclusions/Interpretation:Thus, the Gly482Ser polymorphism may predict a more favorable metabolic and inflammatory outcome for obese patients submitted to bariatric surgery, leading to a reduced atherosclerotic risk. [ABSTRACT FROM AUTHOR]

Energy homeostasis involves a complex network of hypothalamic and extra-hypothalamic neurons that transduce hormonal, nutrient and neuronal signals into responses that ultimately match caloric intake to energy expenditure and thereby promote stability of body fat stores. Growing evidence suggests that rather than reflecting a failure to regulate caloric intake, common forms of obesity involve fundamental changes to this homeostatic system that favor the defense of an elevated level of body adiposity. This article reviews emerging evidence that during high-fat feeding, obesity pathogenesis involves fundamental alteration of hypothalamic systems that regulate food intake and energy expenditure. [ABSTRACT FROM AUTHOR]

High-dose aspirin treatment improves fasting and postprandial hyperglycaemia in patients with type 2 diabetes, as well as in animal models of insulin resistance associated with obesity and sepsis. In this study, we investigated the effects of aspirin treatment on inducible nitric oxide synthase (iNOS)-mediated insulin resistance and on S-nitrosylation of insulin receptor (IR)-β, IRS-1 and protein kinase B (Akt) in the muscle of diet-induced obese rats and also in iNos (also known as Nos2)−/− mice on high fat diet. Aspirin (120 mg kg−1 day−1 for 2 days) or iNOS inhibitor ( L-NIL; 80 mg/kg body weight) were administered to diet-induced obese rats or mice and iNOS production and insulin signalling were investigated. S-nitrosylation of IRβ/IRS-1 and Akt was investigated using the biotin switch method. iNOS protein levels increased in the muscle of diet-induced obese rats, associated with an increase in S-nitrosylation of IRβ, IRS-1 and Akt. These alterations were reversed by aspirin treatment, in parallel with an improvement in insulin signalling and sensitivity, as measured by insulin tolerance test and glucose clamp. Conversely, while aspirin reversed the increased phosphorylation of IκB kinase β and c-Jun amino-terminal kinase, as well as IRS-1 serine phosphorylation in diet-induced obese rats and iNos −/− mice on high-fat diet, these alterations were not associated with the improvement of insulin action induced by this drug. Our data demonstrate that aspirin treatment not only reduces iNOS protein levels, but also S-nitrosylation of IRβ, IRS-1 and Akt. These changes are associated with improved insulin resistance and signalling, suggesting a novel mechanism of insulin sensitisation evoked by aspirin treatment. [ABSTRACT FROM AUTHOR]

Pouchitis after total rectocolectomy is among the most common complications of patients with ulcerative colitis (UC). However, its frequency is quite rare in patients with familial adenomatous polyposis (FAP). We evaluated the inflammatory and pro-apoptotic activity in endoscopically normal mucosa of the ileal pouch in patients with UC and FAP. Twenty patients (10 with UC and 10 with FAP) with “J” pouch after total proctocolectomy were studied as were 10 normal controls. Biopsies were obtained from the mucosa of the pouch of UC and FAP patients and from the normal ileum of controls. The expression levels of TNF-α, IL-1β, IL-6, IL-8 and phospho-BAD were determined by immunoblotting. Activated NFκB was evaluated by immuno-precipitation and immunoblotting for IkappaB kinase beta. Patients with UC had higher levels of IL-1β, IL-6, IL-8 and TNF-α than patients with FAP. The level of TNF-α was higher in patients with UC than in patients with FAP; both patient groups had TNF-α levels higher than controls. Activation of NFκB was similar in all three groups. The expression of phospho-BAD was significantly lower in patients with FAP than in patients with UC. As compared with patients with FAP, patients with UC presented increased levels of some pro-inflammatory cytokines, even in the absence of clinical or endoscopic signs of pouchitis. Patients with FAP presented lower levels of pro-inflammatory proteins and of phospho-BAD. These findings may explain the higher rates of progression to pouchitis in UC patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. [ABSTRACT FROM AUTHOR]

Diet-induced obesity (DIO) is associated with insulin resistance in liver and muscle, but not in adipose tissue. Mice with fat-specific disruption of the gene encoding the insulin receptor are protected against DIO and glucose intolerance. In cell culture, glutamine induces insulin resistance in adipocytes, but has no effect in muscle cells. We investigated whether supplementation of a high-fat diet with glutamine induces insulin resistance in adipose tissue in the rat, improving insulin sensitivity in the whole animal. Male Wistar rats received standard rodent chow or a high-fat diet (HF) or an HF supplemented with alanine or glutamine (HFGln) for 2 months. Light microscopy and morphometry, oxygen consumption, hyperinsulinaemic–euglycaemic clamp and immunoprecipitation/immunoblotting were performed. HFGln rats showed reductions in adipose mass and adipocyte size, a decrease in the activity of the insulin-induced IRS–phosphatidylinositol 3-kinase (PI3-K)–protein kinase B–forkhead transcription factor box 01 pathway in adipose tissue, and an increase in adiponectin levels. These results were associated with increases in insulin-stimulated glucose uptake in skeletal muscle and insulin-induced suppression of hepatic glucose output, and were accompanied by an increase in the activity of the insulin-induced IRS–PI3-K–Akt pathway in these tissues. In parallel, there were decreases in TNFα and IL-6 levels and reductions in c-jun N-terminal kinase (JNK), IκB kinase subunit β (IKKβ) and mammalian target of rapamycin (mTOR) activity in the liver, muscle and adipose tissue. There was also an increase in oxygen consumption and a decrease in the respiratory exchange rate in HFGln rats. Glutamine supplementation induces insulin resistance in adipose tissue, and this is accompanied by an increase in the activity of the hexosamine pathway. It also reduces adipose mass, consequently attenuating insulin resistance and activation of JNK and IKKβ, while improving insulin signalling in liver and muscle. [ABSTRACT FROM AUTHOR]

Ghrelin is a peptide that is mainly produced by the stomach and stimulates food intake, adiposity and weight gain. Previous studies have documented that plasma levels of ghrelin are reduced by insulin, but the mechanisms that mediate this effect are unclear. To determine whether phosphatidylinositol 3-kinase (PI(3)K) and/or mitogen-activated protein kinase (MAPK) are involved in this insulin action, we tested the intracerebroventricular (i.c.v.) effect of specific inhibitors of PI(3)K (LY294002 and wortmannin) and MAPK (PD98059 and UO126) on the insulin-mediated reduction of ghrelin levels in rats. Intracerebroventricular treatment with insulin reduced ghrelin levels. Inhibition of PI(3)K specifically blocked the insulin-induced reduction in ghrelin concentration, whereas inhibition of MAPK had no effect on insulin-mediated actions. Moreover, pretreatment with i.c.v. PI(3)K inhibitors blocked the reduction of ghrelin levels after OGTT-induced hyperglycaemia and hyperinsulinaemia. These data demonstrate that changes in insulin action in the central nervous system regulate circulating ghrelin levels and that PI(3)K is a specific mediator of this action. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: To assess the involvement of the AGE-specific receptor (AGER, also known as RAGE) axis and nuclear factor kappa-B (NFKB, also known as NF-kappaB) activation in the development of lacrimal gland and tear film dysfunction in diabetes, the present study evaluated: (1) lacrimal gland and tear film alterations in diabetic rats; and (2) the expression of AGE, AGER and NFKB in ocular tissues of normoglycaemic and diabetic rats. Materials and Methods: Diabetes was induced in male Wistar rats with intravenous streptozotocin. Tear secretion parameters were measured and NFKB expression was evaluated in lacrimal glands of control and diabetic rats by western blot. Immunohistochemistry with confocal microscopy was used to assess AGE, AGER and NFKB expression in lacrimal glands of both groups. Results: Lacrimal gland weight and tear film volume were lower in diabetic than in control rats (p=0.01 and 0.02, respectively). IL1B and TNF concentrations in tears were higher in diabetic than in control rats (p=0.007 and 0.02, respectively). NFKB protein was identified in rat cornea, conjunctiva and lacrimal glands. AGE, AGER and NFKB expression were greater in lacrimal glands of diabetic than in those of control rats. Conclusions/interpretation: Diabetes induces significant alterations in rat lacrimal gland structure and secretion. The higher expression of AGE, AGER and NFKB in lacrimal glands of diabetic rats suggests that these factors are involved in signalling and in subsequent inflammatory alterations related to dry eye in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The coactivator of nuclear receptors, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has been implicated in a series of events that contribute to the control of glucose metabolism. We have recently reported the use of a PGC-1α antisense oligonucleotide (PGC-1αAS) that inhibits up to 60% of PGC-1α expression in pancreatic islets, leading to increased insulin secretion. This oligonucleotide was used in this study to try to ameliorate diet-induced type 2 diabetes in a genetically predisposed mouse strain (Swiss mice). Materials and methods: Glucose and insulin tolerance tests, euglycaemic-hyperinsulinaemic clamp, immunoprecipitation assays, immunoblotting assays and immunohistochemistry were used in this investigation. Results: Swiss mice became obese and overtly diabetic after 8 weeks of feeding with chow containing 24% saturated fat. One daily dose (1.0 nmol) of PGC-1αAS significantly reduced glucose and increased insulin blood levels without affecting food intake and body weight. These effects were accompanied by a reduced area under the glucose curve during an intraperitoneal glucose tolerance test, an increased constant of glucose decay (Kitt) during an insulin tolerance test, and an increased glucose consumption rate during a euglycaemic-hyperinsulinaemic clamp. Moreover, mice treated with PGC-1αAS presented an outstanding reduction of macroscopic and microscopic features of hepatic steatosis. These effects were accompanied by reduced expression or function of a series of proteins involved in lipogenesis. Conclusions/interpretation: PGC-1α is an attractive target for pharmacological therapeutics in type 2 diabetes mellitus and diet-induced hepatic steatosis. [ABSTRACT FROM AUTHOR]

Aim/hypothesis. By acting in the brain, insulin suppresses food intake. However, little is known with regard to insulin signalling in the hypothalamus in insulin-resistant states. Methods. Western blotting, immunohistochemistry and polymerase chain reaction assays were combined to compare in vivo hypothalamic insulin signalling through the PI3-kinase and MAP kinase pathways between lean and obese Zucker rats. Results. Intracerebroventricular insulin infusion reduced food intake in lean rats to a greater extent than that observed in obese rats, and pre-treatment with PI3-kinase inhibitors prevented insulin-induced anorexia. The relative abundance of IRS-2 was considerably higher than that of IRS-1 in hypothalamus of both lean and obese rats. Insulin-stimulated phosphorylation of IR, IRS-1/2, the associations of PI 3-kinase to IRS-1/2 and phosphorylation of Akt in hypothalamus were decreased in obese rats compared to lean rats. These effects seem to be mediated by increased phosphoserine content of IR, IRS-1/2 and decreased protein levels of IRS-1/2 in obese rats. In contrast, insulin stimulated the phosphorylation of MAP kinase equally in lean and obese rats. Conclusion/interpretation. This study provides direct measurements of insulin signalling in hypothalamus, and documents selective resistance to insulin signalling in hypothalamus of Zucker rats. These findings provide support for the hypothesis that insulin could have anti-obesity actions mediated by the PI3-kinase pathway, and that impaired insulin signalling in hypothalamus could play a role in the development of obesity in this animal model of insulin-resistance. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Sympathetic inputs inhibit insulin secretion through α2-adrenergic receptors coupled with Gi protein. High adrenergic tonus generated by exposure of homeothermic animals to cold reduces insulin secretion. In this study we evaluate the participation of UCP-2 in cold-induced regulation of insulin secretion. Methods. Static insulin secretion studies, western blotting and immunohistochemistry were used in this investigation. Results. Exposure of rats to cold during 8 days promoted 60% (n=15, p<0.05) reduction of basal serum insulin levels concentration accompanied by reduction of the area under insulin curve during i.p. GTT (50%, n=15, p<0.05). Isolated islets from cold-exposed rats secreted 57% (n=6, p<0.05) less insulin following a glucose challenge. Previous sympathectomy, partially prevented the effect of cold exposure upon insulin secretion. Islets isolated from cold-exposed rats expressed 51% (n=6, p<0.5) more UCP-2 than islets from control rats, while the inhibition of UCP-2 expression by antisense oligonucleotide treatment partially restored insulin secretion of islets obtained from cold-exposed rats. Cold exposure also induced an increase of 69% (n=6, p<0.05) in PGC-1 protein content in pancreatic islets. Inhibition of islet PGC-1 expression by antisense oligonucleotide abrogated cold-induced UCP-2 expression and partially restored insulin secretion in islets exposed to cold. Conclusion/interpreatation. Our data indicate that sympathetic tonus generated by exposure of rats to cold induces the expression of PGC-1, which participates in the control of UCP-2 expression in pancreatic islets. Increased UCP-2 expression under these conditions could reduce the beta-cell ATP/ADP ratio and negatively regulate insulin secretion. [ABSTRACT FROM AUTHOR]

Pregnancy is known to induce insulin resistance, but the exact molecular mechanism involved is unknown. In the present study, we have examined the levels and phosphorylation state of the insulin receptor and of insulin receptor substrate 1(IRS-1), as well as the association between IRS-1 and phosphatidylinositol 3-kinase (PI 3-kinase) in the liver and muscle of pregnant rats (day 20 of gestation) by immunoprecipitation and immunoblotting with anti-insulin receptor, anti-IRS-1, anti-PI 3-kinase and anti-phosphotyrosine antibodies. There were no changes in the insulin receptor concentration in the liver and muscle of pregnant rats. However, insulin stimulation of receptor autophosphorylation, as determined by immunoblotting with antiphosphotyrosine antibody, was reduced by 30 ± 6 % ( p < 0.02) in muscle and 36 ± 5 % ( p < 0.01) in liver at day 20 of gestation. IRS-1 protein levels decreased by 45 ± 6 % ( p < 0.002) in liver and by 56 ± 9 % ( p < 0.002) in muscle of pregnant rats. In samples previously immunoprecipitated with anti-IRS-1 antibody and blotted with antiphosphotyrosine antibody, the insulin-stimulated IRS-1 phosphorylation levels in the muscle and liver of pregnant rats decreased by 70 ± 9 % ( p < 0.01) and 75 ± 8 % ( p < 0.01), respectively. The insulin-stimulated IRS-1 association with PI 3-kinase decreased by 81 ± 6 % in muscle ( p < 0.01) and 79 ± 11 % ( p < 0.01) in the liver during pregnancy. These data suggest that changes in the early steps of insulin signal transduction may have a role in the insulin resistance observed in pregnancy. [Diabetologia (1997) 40: 179–186] [ABSTRACT FROM AUTHOR]

To clarify whether GAD-ab are associated with diabetic autonomic neuropathy and/or complement fixing antibodies against sympathetic ganglia, adrenal medulla, and vagus nerve, we examined 133 diabetic patients (95 with IDDM). GAD-ab were determined by a radioligand binding assay using in vitro expression of recombinant GAD-65 whereas sympathetic ganglia antibodies, adrenal medulla antibodies, vagus nerve, and ICA were evaluated by indirect immunofluorescence assays. Autonomic nerve function was evaluated by objective tests (heart rate reactions to deep breathing and to tilt). In the total material of 133 patients, GAD-ab were detected in 36 patients, all of whom had IDDM. The frequency of GADab was similar (38%) in IDDM patients with and without signs of autonomic neuropathy (21 of 55 vs 15 of 40). In addition, there were no significant associations between GAD-ab and autonomic nerve antibodies; GAD-ab were detected in 9 of 21 (43%) of patients with and in 27 of 112 (24%) of patients without sympathetic ganglia antibodies, in 5 of 15 (33%) of patients with and 31 of 118 (26%) without adrenal medulla antibodies, and in 5 of 15 (33%) with and 31 of 118 (26%) of patients without vagus nerve antibodies. The frequency of ICA, however, was significantly increased in patients with sympathetic ganglia antibodies compared with those without sympathetic ganglia antibodies (10 of 21 [48%] vs 21 of 112 [19%]; p<0.01). In conclusion, GAD-ab were neither associated with disturbed autonomic nerve function nor with antibodies against autonomic nerve structures. [ABSTRACT FROM AUTHOR]

Beta-cell function and islet cell antibodies were studied in six patients with autoimmune polyendocrine syndrome type I. All suffered from mucocutaneous candidiasis, five had adrenocortical insufficiency and three hypoparathyroidism. All sera contained high titres of antibodies staining islets of Langerhans. Reactivity against glutamate decarboxylase, predominantly the 65 kDa isoform, was detected by immunoprecipitations and Western blots in five of the six sera, and all six sera immunoprecipitated a 51 kDa antigen from [S]methionine labelled rat islet cell lysates. No reactivity against this latter antigen was found in sera of patients with Type 1 (insulin-dependent) diabetes mellitus ( n=9), Graves' disease ( n=5), autoimmune gastritis ( n=4), idiopathic Addison's disease ( n=7), or stiffman syndrome ( n=2). The 51 kDa antigen was also detected by Western blots using homogenates of rat islets and autoimmune polyendocrine syndrome type I patient sera, whereas no such reactivity was found with homogenates of testes, adrenals, small intestine, spleen, exocrine pancreas or brain. Moreover, the 51 kDa antigen was present in the rat insulinoma cell line RINm 5F but not in the SV-40 transformed, monkey kidney cell line COS, when examined by immunoprecipitations of [S]-methionine labelled cell lysates and by Western blots. None of the patients with autoimmune polyendocrine syndrome type I had symptoms of diabetes and their insulin responses to glucose challenge were normal. The data illustrate that patients with autoimmune polyendocrine syndrome type I present an autoimmune response against islets of Langerhans, which is apparently different from that associated with classic Type 1 diabetes. As most of the autoantigens in many autoimmune diseases are enzymes involved in important functions in the affected organs, it is possible that the anti-51 kDa antibodies are directed against a protein with important functional activity in the islet. [ABSTRACT FROM AUTHOR]

The presence of one of the major targets for auto-antibodies in Type 1 (insulin-dependent) diabetes mellitus, the enzyme glutamic acid decarboxylase, was studied in human, rat and mouse pancreatic tissue using immunoprecipitation and immunohistochemical techniques. Immunoprecipitation of glutamic acid decarboxylase was attempted with lysates of [S]-methionine-labelled rat or mouse pancreatic islets using two different glutamic acid decarboxylase antisera, one mouse monoclonal antibody raised against the 65 kDa isoform of the enzyme, sera from six patients with Type 1 diabetes, one patient with stiff-man syndrome and sera from 19 non-obese diabetic mice. The same sera were used for immunoperoxidase staining of cryosections of human, rat or mouse pancreas. Using patient sera glutamic acid decarboxylase was detected by immunoprecipitations from isolated rat islets but not from islets of five different mouse strains tested, including the non-obese diabetic mouse. When using the non-obese diabetic mouse sera, glutamic acid decarboxylase could not be detected in either rat or mouse tissue. Immunoperoxidase staining demonstrated high levels of glutamic acid decarboxylase in human and rat pancreatic islets but low levels in mouse islets. Direct measurements of enzyme activity showed glutamic acid decarboxylase to be present in mouse islets at a level of about 40% of that in rat islets, and subsequent Western blot analyses indicated that mouse islets express the 67 kDa isoform, whereas in rat islets both the 67 and 65 kDa isoforms are present. The species difference at the level of one of the major islet cell autoantigens in Type 1 diabetes thus indicates that human or rat and mouse islets, respectively, express immunologically distinct forms of glutamic acid decarboxylase and differ in their way of regulating the enzyme production. [ABSTRACT FROM AUTHOR]

The article discusses the investigation of the role of p22-phox-930A/G polymorphism on end-organ damage in hypertensive patients. The study involves 194 hypertensive patients followed up at the Hypertension Unit of State University of Campinas in Brazil and in 70 normotensive volunteers recruited between January 2005 and December 2006. Results provide no support to the hypothesis that p22-phox-930A/G polymorphism is involved in cardiac/renal injury induced by hypertension.

In light of forensic evidence indicating duplication and/or manipulation of western blot images the Editor-in-Chief is retracting the article cited above. [ABSTRACT FROM AUTHOR]