Summary The l ‐guluronic acid residues in the Azotobacter vinelandii polysaccharide alginate originate from a post‐polymerization reaction catalysed by enzyme mannuronan C‐5‐epimerase (ME). We have previously reported cloning and expression of an A. gene encoding this enzyme, we show here that organism encodes at least four other ME genes originating common ancestor complex rearrangement process. biological function corresponding enzymes is probably to catalyse formation alginates with...

Low birthweight (LBW) has emerged as a risk factor of metabolic syndrome (MetS). Whether adults with very low (VLBW) born preterm are at higher than individuals who were term-born small for gestational age (tb-SGA) is not established. We assessed outcomes, including relation skeletal parameters, in these two LBW categories. This follow-up cohort study included 189 (females 51%), aged 25 to 28 years; 55 VLBW (≤1500 g), 59 tb-SGA (<10th percentile), and 75 controls (≥10th percentile). Outcomes...

The purpose of this pilot study was to investigate if sleep classification data from a non-contact monitor placed in the patient's bedroom at home were associated with obstructive apnea (OSA) severity time primary investigation. Secondly, we aimed effect established continuous positive airway pressure (CPAP) therapy on objective measurements. We performed prospective single center medium size hospital. Adult patients referred symptoms that could indicate OSA underwent standard respiratory...

Chronic hyperglycemia impairs mitochondrial function of beta cells. Changes in preceding a negative glucose effect have not been fully characterized, nor interactions with ketones. To compare effects on cell by short and longer exposures to elevated ketones oxygen consumption rate (OCR) was measured intact clonal cells an OROBOROS rat islets Seahorse instrument. Proteins (subunits) complexes (C) were immunoblotting. ATP ROS islets. In INS-1 832/13 cells, overnight exposure 27 vs. 11 mm...

Abstract Aims To compare outcomes of glucagon‐stimulated C‐peptide tests (GSCTs) in people with latent autoimmune diabetes adults (LADA) after a 21‐month intervention either insulin or the dipeptidyl peptidase‐4 inhibitor sitagliptin. Research design and methods We included 64 glutamic acid decarboxylase (GAD) antibody‐positive individuals, who were diagnosed &lt;3 years before study, aged 30 to 70 years, without clinical need for treatment. stratified participants by age body mass index...

We investigated the impact of a diabetic state with hyperglycemia on morphometry β cell mitochondria and modifying influence K+-ATP channel opener we related in vivo findings glucose effects vitro. For experiments islets from syngeneic rats were transplanted under kidney capsule to neonatally streptozotocin-diabetic or non-diabetic recipients. Diabetic recipients received vehicle, tifenazoxide (NN414), intragastrically for 9 weeks. Non-diabetic vehicle. Transplants excised 7 d after...

Objective Beta cells of pancreatic islets are susceptible to functional deficits and damage by hypoxia. Here we aimed characterize such effects test for pharmacological means alleviate a negative impact Methods Design Rat human were subjected 5.5 h hypoxia after which viability parameters measured subsequent the hypoxic period and/or following 22 re-oxygenation period. Preconditioning with diazoxide or other agents was usually done during prior Results Insulin contents decreased 23% 61%...

Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death early posttransplantation period. Here we tested susceptibility alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O 2 for 8 h, followed reoxygenation) on viability and functional parameters. Hypoxia reduced as measured MTT by<mml:math...

Objective To provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia. Methods Design Insulin-producing INS-1 832/13 cells were exposed to 18 hours hypoxia followed by 20–22 re-oxygenation. Mitochondrial was measured high-resolution respirometry both intact permeabilized cells, latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins complexes (Western blotting),...

OBJECTIVE Continuous β-cell rest with diazoxide preserves residual endogenous insulin production in type 1 diabetes. However, side effects have hampered therapeutic usefulness. In a double-blind study, we tested whether lower, intermittent dosing of had beneficial on production, metabolic control, and autoimmunity markers the absence effects. RESEARCH DESIGN AND METHODS Forty-one newly diagnosed diabetic patients were randomized to 6 months treatment placebo or 100 mg at bedtime. A1C,...

Background Latent Autoimmune Diabetes in Adults (LADA) constitutes around 10% of all diabetes. Many LADA patients gradually lose their insulin secretion and progress to dependency. In a recent trial BALAD (Behandling Av LADa) early treatment compared with sitagliptin failed preserve secretion, which deteriorated individuals displaying high levels antibodies GAD (GADA). These findings prompted us evaluate that directly affects autoimmunity. Intra-lymphatic GAD-alum has shown encouraging...

We previously showed that hyperoxia in vitro negatively affects beta cells of the rat. Here, we tested for possible clinical significance as well mitochondrial interactions by hyperoxia, using human islets (function and viability), INS-1 832/13 (mitochondrial metabolism), mouse neonates (effects vivo). Lastly, assessed relevant parameters a cohort individuals born preterm then exposed to hyperoxia. Human were 24 h (90–92% oxygen). Mouse subjected 5 days continuous Individuals evaluated terms...

We tested whether exposure of β cells at reduced glucose leads to mitochondrial adaptions and such modulate effects hypoxia. Rat islets, human islets INS-1 832/13 were pre-cultured short term half standard concentrations (5.5 mM for rat cells, 2.75 islets) without overtly negative on subsequently measured function (insulin secretion cellular insulin contents) or viability. Culture upregulated complex I tended upregulate II in alike. An increased release lactate dehydrogenase that followed...

Cytokines and chemokines participate in autoimmune processes at cellular targets which include insulin-producing beta cells. To extent such participation is reflected the circulation has not been conclusively resolved.We compared time course of cytokines/chemokines Latent Autoimmune Diabetes Adults (LADA) patients heterogeneous for high or low activity as determined by levels antibodies against glutamic acid decarboxylase (GADA).Serum samples to be measured were from a two-armed randomized...

To test, for the first time in latent autoimmune diabetes adults (LADA), effects of autoantigen-specific immunotherapy by intralymphatic administration aluminium-formulated recombinant human glutamic acid decarboxylase 65 (GAD-alum); specifically, to test if this treatment is safe, whether it induces a strong immunological response akin similar protocol type 1 and look associations with preserved beta-cell function.Three GAD-alum injections, 4 μg each, were administered month apart into an...