Resistance exercise training lowers HbA1c more than aerobic training in adults with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to compare the effects of 10 weeks of resistance or treadmill exercises on glycemic indices levels prior to and immediately following exercise in adults with type 2 diabetes.</p> <p>Research Design and Method</p> <p>Twenty inactive subjects (mean age 53.5 years) with type 2 diabetes enrolled in the study. Baseline HbA1c, blood glucose levels, heart rate, and blood pressure were measured for each subject prior to the initiation of the exercise program. Subsequently, subjects were matched to age, waist circumference and sex and assigned to either isocaloric resistance or treadmill exercise groups, which met 3 times per week for 10 weeks.</p> <p>Results</p> <p>Both groups showed a reduction in pre and post-exercise blood glucose and HbA1c values. There was no change in resting blood pressure or heart rate in either group during the course of the 10 week intervention. The group receiving resistance exercises showed significant differences in the daily pre-exercise plasma glucose readings between the beginning and end of the exercise protocol (p < 0.001). There were significant improvements in the mean HbA1c reading pre and post training in both groups (p < 0.001). However, the greater reduction was noted in the resistance exercise group, and at 10 weeks their HbA1c levels were significantly lower than the group that received treadmill exercises (p < 0.006).</p> <p>Conclusion</p> <p>Ten weeks of resistance exercises were associated with a significantly better glycemic control in adults with type 2 diabetes compared to treadmill exercise.</p

Pancreatic islet transplantation to treat diabetes - defining molecular tools to select suitable islets [abstract]

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionA complete understanding of pancreatic islet biology is essential to the development of preventive or curative interventions for diabetes. It has been known that subpopulations of islets of different sizes exist; however, whether they are biologically and functionally unique has not been investigated. As an example, our work comparing the biology of large versus small islets isolated from rats showed that small islets were superior to large islets in in vitro function and in transplantation outcomes. These results provided the stimulus for an improved approach to islet transplantation in humans. The work also led to new questions regarding the basic physiology of healthy islets. Through collaboration between our University of Kansas Medical Center and Children's Mercy Hospital teams, we determined that small islets secrete higher amount of insulin in vitro when compared to the large islets. We sought to identify whether the islet subpopulations showed differences at the molecular level and thus we investigated their protein expression profiles using two-dimensional polyacrylamide gel electrophoresis (2D PAGE). We found that the protein repertoire in the small and large islets differed significantly. Specifically, some proteins were found only in one type of islets, small or large, while they were missing or their expression levels were different in the other subpopulation. We identified some of the proteins by liquid chromatography - mass spectrometry. Immunofluorescence performed on small and large islets in pancreatic sections, with antibodies against identified proteins, confirmed that the proteins were present in one subpopulation of islets. Of these proteins, at least one was unique to large islets and can potentially be used as a marker to distinguish in vivo between islets that are high-insulin producers and those that fail to secrete significant amounts in insulin. Our long-term goal is to monitor the fate of the different islet populations during diabetes development. In addition, markers like this can be used to determine the best islet subpopulation for transplantation. The data support our hypothesis that integral differences exist between small and large islets that might determine the islets' unique properties under normal conditions and during the development of diabetes. These differences may also influence islet subpopulation behavior in transplantation affecting the outcome

Elimination of T cell reactivity to pancreatic β cells and partial preservation of β cell activity by peptide blockade of LFA-1:ICAM-1 interaction in the NOD mouse model

In insulin dependent diabetes mellitus (T1D), self-reactive T cells infiltrate pancreatic islets and induce beta cell destruction and dysregulation of blood glucose. A goal is to control only the self-reactive T cells, leaving the remainder of the T cell population free to protect the host. One approach is blockade of the second signal for T cell activation while allowing the first (antigen-specific) signal to occur. This work proposes that small peptides that block interaction of second signals delivered through the counter receptors LFA-1:ICAM-1 will induce attacking T cells (receiving the antigen signal) to become anergic or undergo apoptosis. In NOD mice, the peptides eliminated T cell reactivity against pancreatic antigens and reduced cellular infiltration into islets, which retained stronger density of insulin staining at five weeks after cessation of therapy. In in vitro studies the peptides induced nonresponsiveness during activation of T cells from mice and from human peripheral blood

Electrocardiographic changes with the onset of diabetes and the impact of aerobic exercise training in the Zucker Diabetic Fatty (ZDF) rat

BACKGROUND: Early markers of diabetic autonomic neuropathy (DAN) in an electrocardiogram (ECG) include elevated R wave amplitudes, widening of QT(c )intervals and decreased heart rate variability (HRV). The severity of DAN has a direct relationship with mortality risk. Aerobic exercise training is a common recommendation for the delay and possible reversal of cardiac dysfunction. Limited research exists on ECG measures for the evaluation of aerobic exercise training in Zucker Diabetic Fatty (ZDF) rat, a model of type 2 diabetes. The objective of this study was to assess whether aerobic exercise training may attenuate diabetes induced ECG changes. METHODS: Male ZDF (obese fa/fa) and control Zucker (lean fa/+) rats were assigned to 4 groups: sedentary control (SC), sedentary diabetic (SD), exercised control (EC) and exercised diabetic (ED). The exercised groups began 7 weeks of treadmill training after the development of diabetes in the ED group. Baseline (prior to the training) and termination measurements included body weight, heart weight, blood glucose and glycated hemoglobin levels and ECG parameters. One way repeated measures ANOVA (group) analyzed within and between subject differences and interactions. Pearson coefficients and descriptive statistics described variable relationships and animal characteristics. RESULTS: Diabetes caused crucial changes in R wave amplitudes (p < 0.001), heart rate variability (p < 0.01), QT intervals (p < 0.001) and QT(c )intervals (p < 0.001). R wave amplitude augmentation in SD rats from baseline to termination was ameliorated by exercise, resulting in R wave amplitude changes in ED animals similar to control rats. Aerobic exercise training neither attenuated QT or QT(c )interval prolongation nor restored decreases in HRV in diabetic rats. CONCLUSION: This study revealed alterations in R wave amplitudes, HRV, QT and QT(c )intervals in ZDF rats. Of these changes, aerobic exercise training was able to correct R wave amplitude changes. In addition, exercise has beneficial effect in this diabetic rat model in regards to ECG correlates of left ventricular mass

KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability

KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice

Expression and regulation of nampt in human islets.

Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the mammalian NAD+ biosynthesis of a salvage pathway and exists in 2 known forms, intracellular Nampt (iNampt) and a secreted form, extracellular Nampt (eNampt). eNampt can generate an intermediate product, nicotinamide mononucleotide (NMN), which has been reported to support insulin secretion in pancreatic islets. Nampt has been reported to be expressed in the pancreas but islet specific expression has not been adequately defined. The aim of this study was to characterize Nampt expression, secretion and regulation by glucose in human islets. Gene and protein expression of Nampt was assessed in human pancreatic tissue and isolated islets by qRT-PCR and immunofluorescence/confocal imaging respectively. Variable amounts of Nampt mRNA were detected in pancreatic tissue and isolated islets. Immunofluorescence staining for Nampt was found in the exocrine and endocrine tissue of fetal pancreas. However, in adulthood, Nampt expression was localized predominantly in beta cells. Isolated human islets secreted increasing amounts of eNampt in response to high glucose (20 mM) in a static glucose-stimulated insulin secretion assay (GSIS). In addition to an increase in eNampt secretion, exposure to 20 mM glucose also increased Nampt mRNA levels but not protein content. The secretion of eNampt was attenuated by the addition of membrane depolarization inhibitors, diazoxide and nifedipine. Islet-secreted eNampt showed enzymatic activity in a reaction with increasing production of NAD+/NADH over time. In summary, we show that Nampt is expressed in both exocrine and endocrine tissue early in life but in adulthood expression is localized to endocrine tissue. Enzymatically active eNampt is secreted by human islets, is regulated by glucose and requires membrane depolarization