Successful Versus Failed Adaptation to High-Fat Diet–Induced Insulin Resistance: The Role of IAPP-Induced β-Cell Endoplasmic Reticulum Stress

ObjectiveObesity is a known risk factor for type 2 diabetes. However, most obese individuals do not develop diabetes because they adapt to insulin resistance by increasing beta-cell mass and insulin secretion. Islet pathology in type 2 diabetes is characterized by beta-cell loss, islet amyloid derived from islet amyloid polypeptide (IAPP), and increased beta-cell apoptosis characterized by endoplasmic reticulum (ER) stress. We hypothesized that IAPP-induced ER stress distinguishes successful versus unsuccessful islet adaptation to insulin resistance.Research design and methodsTo address this, we fed wild-type (WT) and human IAPP transgenic (HIP) rats either 10 weeks of regular chow or a high-fat diet and prospectively examined the relations among beta-cell mass and turnover, beta-cell ER stress, insulin secretion, and insulin sensitivity.ResultsA high-fat diet led to comparable insulin resistance in WT and HIP rats. WT rats compensated with increased insulin secretion and beta-cell mass. In HIP rats, in contrast, neither beta-cell function nor mass compensated for the increased insulin demand, leading to diabetes. The failure to increase beta-cell mass in HIP rats was the result of ER stress-induced beta-cell apoptosis that increased in proportion to diet-induced insulin resistance.ConclusionsIAPP-induced ER stress distinguishes the successful versus unsuccessful islet adaptation to a high-fat diet in rats. These studies are consistent with the hypothesis that IAPP oligomers contribute to increased beta-cell apoptosis and beta-cell failure in humans with type 2 diabetes

Pulsatility of insulin release – a clinically important phenomenon

The mechanisms and clinical importance of pulsatile insulin release are presented against the background of more than half a century of companionship with the islets of Langerhans. The insulin-secreting β-cells are oscillators with intrinsic variations of cytoplasmic ATP and Ca2+. Within the islets the β-cells are mutually entrained into a common rhythm by gap junctions and diffusible factors (ATP). Synchronization of the different islets in the pancreas is supposed to be due to adjustment of the oscillations to the same phase by neural output of acetylcholine and ATP. Studies of hormone secretion from the perfused pancreas of rats and mice revealed that glucose induces pulses of glucagon anti-synchronous with pulses of insulin and somatostatin. The anti-synchrony may result from a paracrine action of somatostatin on the glucagon-producing α-cells. Purinoceptors have a key function for pulsatile release of islet hormones. It was possible to remove the glucagon and somatostatin pulses with maintenance of those of insulin with an inhibitor of the P2Y1 receptors. Knock-out of the adenosine A1 receptor prolonged the pulses of glucagon and somatostatin without affecting the duration of the insulin pulses. Studies of isolated human islets indicate similar relations between pulses of insulin, glucagon, and somatostatin as found during perfusion of the rodent pancreas. The observation of reversed cycles of insulin and glucagon adds to the understanding how the islets regulate hepatic glucose production. Current protocols for pulsatile intravenous infusion therapy (PIVIT) should be modified to mimic the anti-synchrony between insulin and glucagon normally seen in the portal blood

SRAP technique efficiently generates polymorphisms in puccinia striiformis isolates

Wheat stripe rust, caused by the fungal pathogen Puccinia striiformis f.sp. tritici (PST), is a major disease of wheat in temperate-cold climates. The identification of new markers would ease the procedure for evaluating the ongoing pathogen evolution. Twelve single pustule isolates were generated from samples of PST obtained in UK during 1987-2001. They were evaluated for their pathogenic behaviour on a set of differential cultivars and were analysed by sequence-related amplified polymorphisms (SRAP) technique, to identify polymorphisms useful to evaluate variability among isolates. This is the first report of the application of SRAP technique to Uredinales order

Outcome of Surgical Treated Isolated Pronator Teres Syndromes—A Retrospective Cohort Study and Complete Review of the Literature

Purpose: This study aims to elucidate the occurrence of postoperative carpal tunnel syndrome (CTS), the functional outcome of patients with primary pronator teres syndrome (PTS), and review complete literature regarding this topic. Material and Methods: A retrospective chart review was conducted in patients with PTS at a single center. In all patients, a numeric Visual Analog Scale (VAS) score, Pinch-Test, Jamar hand dynamometer test (JAMAR), and the Disabilities of the Arm Shoulder and Hand (DASH) score were analyzed preoperatively and at final follow-up to assess outcome. Additionally, a complete review of the literature was performed, including all data dealing with pronator teres syndrome. Results: Ten female and two male patients were included with a mean age of 49 years. Significant improvement in DASH and numeric VAS was detected at latest postoperative follow-up. In three patients, clinical signs of CTS pathology were detected during the follow-up period. One patient needed to be treated surgically, and in the other two patients, a conservative management was possible. In one patient (8%), a PTS recurrence was detected. All patients presented satisfied at latest follow-up. Conclusion: In one-fourth of our patients, a CTS occurred during the follow-up period. Therefore, focusing on double-crush syndrome in unclear or mixed symptoms is necessary to avoid multiple operations. Furthermore, it seems that assessment with NCV is not enough for diagnosing PTS; therefore, further research is needed to clarify this problem

Minimally Invasive AC Joint Reconstruction System (MINAR®) in Modified Triple-Button Technique for the Treatment of Acute AC Joint Dislocation

Acute acromioclavicular (AC) joint dislocation is a frequent sports injury with more than 100 different operation methods described. A total of 65 patients with an acute AC joint dislocation were treated with the modified MINAR® system between 2009 and 2013. Clinical outcome, horizontal and vertical instability, as well as concomitant intraarticular injuries were assessed. We used Zanca, stress and axial X-rays for radiological assessment. A Constant score of 95 (±8.8), University of California Los Angeles Shoulder score (UCLA) of 31 (±4.9), Disabilities of Arm, Shoulder and Hand (DASH) of 9.1 (±14.3), and Visual Analogue Scale (VAS) of 0.9 (±0.126) was found. A total of 30 patients (59%) had no signs of reduction loss, nine patients (18%) a slight loss, 11 patients (22%) a partial loss, and one patient (2%) a total loss. No significant influence on the clinical scores could be shown. The postoperative coracoclavicular (CC) distance negatively affected the Constant (p = 0.007) and UCLA scores (p = 0.035). A longer time interval to surgery had a negative influence on all scores (p ≤ 0.001). We could not find any signs of persistent horizontal instability or intraarticular injuries at follow-up. The MINAR® system promises satisfactory functional and radiological results. When setting the correct indication, patients benefit from an early operation. No persisting horizontal instability was observed following suturing of the AC capsule and the delta fascia

Scientific Reports / Effect of two (short-term) storage methods on load to failure testing of murine bone tissue

Since mechanical testing of bone quality is often delayed following euthanasia, the method of bone storage is of high importance in animal studies. Different storage methods may cause a change in the properties of bone tissue during mechanical testing. Therefore, the aim of this study was to investigate the biomechanical effects of two different fixation methods for bone tissue. We hypothesized that there is a difference between the load to failure values between the two groups. The tibias of fifteen 18-week-old female C57BL/6 mice were harvested and randomly allocated to three different groups with varying storage methods: (1) frozen at 80C, (2) paraformaldehyde working solution, and (3) native group. A storage time of two weeks prior to testing was chosen for groups 1 and 2. In group 3, referred to as the “native group”, bones were immediately tested after the harvesting procedure. The comparison of the mean load to failure of all 3 groups (group 1: 28.7N6.1N, group 2: 23.8N3.8N and group 3: 23.7N5.7N) did not reveal a significant difference. There was also no difference in strength or stiffness. The findings of the present study demonstrate that the two most common storage methods, do not have an influence on the biomechanical properties of murine bone over a two week period.(VLID)493217

Angiotensin II-mediated endothelial dysfunction: role of poly(ADP-ribose) polymerase activation

Angiotensin II (AII) contributes to the pathogenesis of many cardiovascular disorders. Oxidant-mediated activation of poly(adenosine diphosphate–ribose) polymerase (PARP) plays a role in the development of endothelial dysfunction and the pathogenesis of various cardiovascular diseases. We have investigated whether activation of the nuclear enzyme PARP contributes to the development of AII-induced endothelial dysfunction. AII in cultured endothelial cells induced DNA single-strand breakage and dose-dependently activated PARP, which was inhibited by the AII subtype 1 receptor antagonist, losartan; the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, apocynin; and the nitric oxide synthase inhibitor, N-nitro-l-arginine methyl ester. Infusion of sub-pressor doses of AII to rats for 7 to 14 d induced the development of endothelial dysfunction ex vivo. The PARP inhibitors PJ34 or INO-1001 prevented the development of the endothelial dysfunction and restored normal endothelial function. Similarly, PARP-deficient mice infused with AII for 7 d were found resistant to the AII-induced development of endothelial dysfunction, as opposed to the wild-type controls. In spontaneously hypertensive rats there was marked PARP activation in the aorta, heart, and kidney. The endothelial dysfunction, the cardiovascular alterations and the activation of PARP were prevented by the angiotensin-converting enzyme inhibitor enalapril. We conclude that AII, via AII receptor subtype 1 activation and reactive oxygen and nitrogen species generation, triggers DNA breakage, which activates PARP in the vascular endothelium, leading to the development of endothelial dysfunction in hypertension