The unfolded protein response, which is activated during ER stress, counteracts stress conditions by increasing folding capacity and by increasing the degradation of misfolded ER proteins by the ER-Associated Degradation (ERAD) system. Studies using an engineered insulinoma cell line with inducible expression of the Akita folding-deficient insulin have shown a large induction of Herp, a protein that has been implicated in the ERAD pathway. We hypothesized that Herp is an essential protein that regulates the degradation of misfolded insulin during the ER stress response. Indeed, we found that the degradation of mutant insulin is Herp-dependent and that maintaining Herp expression is vital for maintaining cell survival. We have also observed that the expression of Herp mRNA and protein is induced in various cell culture and animal models of diabetes. These results suggest that Herp is an important ER stress response protein that is induced under diabetic conditions in pancreatic β-cells.

The unfolded protein response, which is activated during ER stress, counteracts stress conditions by increasing folding capacity and by increasing the degradation of misfolded ER proteins by the ER-Associated Degradation (ERAD) system. Studies using an engineered insulinoma cell line with inducible expression of the Akita folding-deficient insulin have shown a large induction of Herp, a protein that has been implicated in the ERAD pathway. We hypothesized that Herp is an essential protein that regulates the degradation of misfolded insulin during the ER stress response. Indeed, we found that the degradation of mutant insulin is Herp-dependent and that maintaining Herp expression is vital for maintaining cell survival. We have also observed that the expression of Herp mRNA and protein is induced in various cell culture and animal models of diabetes. These results suggest that Herp is an important ER stress response protein that is induced under diabetic conditions in pancreatic β-cells.

Chronic hyperglycemia, a hallmark of type 2 diabetes, can decrease β-cell function and mass (β-cell glucotoxicity); however, the mechanisms are incompletely understood. The objective was to examine the mechanisms of β-cell glucotoxicity using in vivo and ex vivo models. The hypothesis is that oxidative stress plays a causal role in high glucose-induced β-cell dysfunction in vivo via pathways that involve endoplasmic reticulum (ER) stress and JNK. The model of β-cell glucotoxicity was achieved by prolonged i.v. glucose infusion (to achieve hyperglycemia). In Study 1, 48h glucose infusion increased total and mitochondrial superoxide levels in islets, and impaired β-cell function in vivo and ex vivo. Co-infusion of the superoxide dismutase mimetic Tempol decreased total and mitochondrial superoxide, and prevented high glucose-induced β-cell dysfunction in vivo and ex vivo. These results suggest that increased superoxide generation plays a role in β-cell glucotoxicity. In Study 2, 48h glucose infusion increased activation of the unfolded protein response (XBP-1 mRNA splicing and phospho-eIF2α levels). This was partially prevented by Tempol. Co-infusion of the chemical chaperone 4-phenylbutyrate with glucose decreased spliced XBP-1 levels, and prevented high glucose-induced β-cell dysfunction in vivo and ex vivo. Co-infusion of 4-phenylbutyrate also decreased total and mitochondrial superoxide induced by high glucose. These results suggest that 1) ER stress plays a causal role in high glucose-induced β-cell dysfunction, and 2) there is a link between oxidative stress and ER stress in high glucose-induced β-cell dysfunction in vivo. In Study 3, JNK inhibition using the inhibitor SP600125 in rats or JNK-1 null mice prevented high glucose-induced β-cell dysfunction ex vivo and in vivo. SP600125 prevented high-glucose-induced β-cell dysfunction without decreasing total and mitochondrial superoxide levels. Both Tempol and 4-phenylbutyrate prevented JNK activation induced by high glucose. These results suggest a role of JNK activation in high glucose-induced β-cell dysfunction downstream of increased superoxide generation and ER stress in vivo. Together, the results suggest that 1) oxidative stress, ER stress and JNK activation are causally involved in β-cell glucotoxicity, and 2) High glucose-induced oxidative stress and ER stress are linked, and both impair β-cell dysfunction via JNK activation in vivo.

Bakgrund: I Sverige har 325 000 människor diagnosen typ 2-diabetes. Sjukdomen ställer stora krav på individen. För att sjuksköterskan ska ge en god omvårdnad behövs kunskaper om patientens individuella behov av stöd. Syfte: Syftet var att beskriva patienters upplevelser av sjuksköterskans stöd vid typ 2-diabetes. Metod: Studien genomfördes som en allmän litteraturstudie där nio vetenskapliga artiklar kvalitetsgranskades och analyserades. Resultat: Patienters upplevelser av sjuksköterskans stöd kategoriserades som emotionellt, informativt och värderande stöd. Viktiga faktorer i sjuksköterskans stöd var gemensamt engagemang, tillit, lindring av bördan, att bli sedd som en individ, kunskap genom information, dialog, kontroll och bekräftelse. Diskussion: Två faktorer diskuterades som påverkade upplevelsen av sjuksköterskans stöd. Hur sjuksköterskan gjorde patienterna delaktiga och tillgodosåg patientens individuella behov ansågs vara väsentligt. Slutsats: Det finns ett behov av att belysa hur patienter upplever sjuksköterskans stöd. Genom att sjuksköterskan har insikt i vad ett gott stöd innebär kan patienten få redskap till sjukdomshantering och ett förbättrat välmående. / Background: In Sweden, 325 000 people have the diagnoses of type 2-diabetes. The disease makes great demands on the individual. The nurse needs knowledge about the patient´s individual needs of support to give good nursing care. Aim: The aim was to describe the patients’ experiences of nurse-support in type 2-diabetes. Method: The study was conducted as a literature review and based upon nine scientific articles that were quality assessed and analyzed. Results: The patients’ experiences of nurse-support were categorized as emotional, informational and evaluative support. Important factors given about the nurse´s support was participation by both nurse and patient, trust, easing the burden, to be seen as an individual, knowledge through information, dialogue, control and acknowledgment. Discussion: Two factors were discussed that affected the patients’ experiences of nurse-support. How the nurse included the patients’ in the recovery and management of their disease and catered to the patient´s individual needs that were considered to be essential. Conclusion: There is a need to highlight how the patients’ experience the nurse's given support. Insight from the nurse into what good support means to the patient can improve disease management and well-being.

No description available.

Background: Self-care is a multi-dimensional concept and has different definitions. Amongthe definitions, Orem’s definition of self-care is more consistent. Orem (1995) argues that,self-care is a personal activity to take care and maintain of own self health and illness andprevention of disease related complications. Aim: The aim of the paper was to investigate the factors that contribute to self-care behavioramong patients with Type 2 DM as argued in the literature. Method: data was collected from the following electronic databases: CINAHL, PubMed,LibHub, SweMed and Google Scholar-to find full texts. Data was analyzed through CriticalAppraisal Skill Programme. To ensure validity and reliability the author were blinded toreduce study bias and articles were selected according their quality. Result: 31 relevant studies were included in the review, among the major findings of the studywere; Age, Social support/network, high income level, high educational attainment and longType 2 DM diagnosis history had a positive predictor in Type 2 DM patients self-carecontributing factors. Conclusion: To improve a Type 2 DM patients self-care activities the present study concludedthat Demographic, Socio-Economic and Social support factors are among the positivecontributors in patients of Type 2 DM successful Self-Care activities. Key words; Blood glucose self-monitoring, self-administration, Self-care, self-medication,Type 2 Diabetes. / The aim of the paper was to investigate the factors that contribute to self-care behavior among patients with Type 2 DM as argued in the literature.

No description available.

The prevalence of insulin resistance and type 2 diabetes mellitus (T2DM) in obese children and adolescents is growing at an alarming rate, especially in ethnic minorities. It is not clear whether young people of different ethnic backgrounds vary in their metabolic response to excessive adiposity. Differences in lipid partitioning in the abdominal fat compartments have been observed among different ethnic groups. The aim of this study was to evaluate whether there are ethnic differences in intramyocellular lipid (IMCL) levels that are related to differences in insulin sensitivity. Eighty-two obese children and adolescents underwent 1) 1H nuclear magnetic resonance (NMR) spectroscopy to non-invasively quantify IMCL levels in their soleus muscle, 2) an oral glucose tolerance test and (in a subset of subjects) a euglycemic-hyperinsulinemic clamp to assess insulin sensitivity, 3) a dual-energy X-ray absorptiometry (DEXA) scan to measure total percent body fat, and 4) magnetic resonance imaging to measure abdominal fat distribution. IMCL levels in Hispanic children and adolescents (1.50 ± 0.64%) were significantly greater than in their Caucasian (1.19 ± 0.40%) and African-American (1.09 ± 0.49%) peers. Visceral fat was significantly lower in African Americans (42.7 ± 18.8cm2) and were similar in Caucasians (70.9 ± 27.5cm2) and Hispanics (77.3 ± 41.9cm2). The three groups were not different with respect to insulin sensitivity. For the entire cohort, IMCL levels were inversely related to insulin sensitivity. There was a significant correlation between visceral fat and insulin resistance in Hispanics and Caucasians but not in African Americans. In conclusion, these data suggest that there are significant ethnic differences in lipid partitioning in both the muscle and abdominal compartment. These findings may explain ethnic differences in insulin sensitivity and further the understanding of the pathogenesis of insulin resistance and T2DM.

Thesis (M.A.)--Indiana University, 2009. / Title from screen (viewed on February 1, 2010). Department of English, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Ulla M. Connor, Frank M. Smith, Honnor Orlando. Includes vitae. Includes bibliographical references (leaves 138-139).

PANcreatic-DERived Factor (PANDER), or FAM3B, is a 235-amino acid protein strongly expressed within and secreted from the endocrine pancreas. Research surrounding PANDER has revealed a large role for the protein in maintaining glucose homeostasis, as evidenced by several Ad-PANDER overexpressing murine models, our lab's pancreas-specific PANDER transgenic overexpressor, and most recently our mixed genetic C57/129J PANDER knockout (PANKO) mouse. However, PANDER's overall role in glycemic regulation and glucose homeostasis has yet to be studied in a purebred C57BL/6J PANDER knockout model. Here we present the first phenotypic characterization of our global PANDER knockout mouse on a C57BL/6J background (PANKO-C57) where we examined metabolics through glucose/insulin tolerance testing, fasting glycemia, and body weights, the concentrations of hormonal analytes along with lipids and corticosterones, and full elucidation of hepatic insulin signaling through the insulin signaling cascade. Overall, the PANKO-C57 mice exhibited increased body weights with enhanced glucose tolerance and lower fasting glycemia, similar peripheral insulin sensitivities, increased hepatic lipidemia, and enhanced hepatic insulin signaling at critical insulin signaling molecules. Taken together, the PANKO-C57 demonstrates that the disruption of PANDER results in selectively enhanced hepatic insulin signaling yet with increased lipidemia and overall body weight. These findings reveal a novel role for PANDER in differentially controlling lipogenesis and hepatic glucose production that may selectively impact overall glycemic control and potentially facilitate the onset and/or progression of type 2 diabetes.