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

Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM

Company Growth and Its Main Factors

Analyzing factors exerting in fluence on the company growth being expressed in production in crease the author divide them into direct factors: manpower resources used in production, their size and qualifications, quality and quantity of work done by those employed in material production, end in direct factors: quality and quantity of means of labour employed in production, fixed and turnover funds employed in production. Further analysis deals with the Influence exerted by lebour productivity (efficiency) on the company growth. While defining the essence of productivity the author comes to the conclusion that the importance of productivity growth lies in the fact that as a main factor of production volume growth, through reduction of costs end price and through in crease of individual incomes it ensures improvement of living standards. The author proceeds next to discussing coefficients used in measuring labour productivity. Further analysis encompasses labour productivity at the national and sectional levels. The article ends with presentation of some indices used for measuring labour productivity.Zadanie pt. „Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki” nr 885/P-DUN/2014 zostało dofinansowane ze środków MNiSW w ramach działalności upowszechniającej naukę

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

Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure

OBJECTIVES: We investigated the effects of a novel ultrapotent poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, PJ34, on cardiac and endothelial dysfunction in a rat model of chronic heart failure (CHF). BACKGROUND: Overactivation of the nuclear enzyme PARP importantly contributes to the development of cell dysfunction and tissue injury in various pathophysiologic conditions associated with oxidative stress, including myocardial reperfusion injury, heart transplantation, stroke, shock, and diabetes. METHODS: Chronic heart failure was induced in Wistar rats by chronic ligation of the left anterior descending coronary artery. Left ventricular (LV) function and ex vivo vascular contractility and relaxation were measured 10 weeks after the surgery. Nitrotyrosine (NT) formation and PARP activation were detected by immunohistochemistry. RESULTS: Chronic heart failure induced increased NT formation and PARP activation in the myocardium and intramural vasculature, depressed LV performance, and impaired vascular relaxation of aortic rings. PJ34 significantly decreased myocardial PARP activation but not NT formation, and improved both cardiac dysfunction and vascular relaxation. CONCLUSIONS: Poly(ADP-ribose) polymerase inhibition represents a novel approach for the experimental treatment of CHF

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