Helga Ellingsgaard

Activation of the innate immune system in obesity is a risk factor for the development of type 2 diabetes. The aim of the current study was to investigate the notion that increased numbers of macrophages exist in the islets of type 2 diabetes patients and that this may be explained by a dysregulation of islet-derived inflammatory factors. Increased islet-associated immune cells were observed in human type 2 diabetic patients, high-fat-fed C57BL/6J mice, the GK rat, and the db/db mouse. When cultured islets were exposed to a type 2 diabetic milieu or when islets were isolated from high-fat-fed mice, increased islet-derived inflammatory factors were produced and released, including interleukin (IL)-6, IL-8, chemokine KC, granulocyte colony-stimulating factor, and macrophage inflammatory protein 1alpha. The specificity of this response was investigated by direct comparison to nonislet pancreatic tissue and beta-cell lines and was not mimicked by the induction of islet cell death. Further, this inflammatory response was found to be biologically functional, as conditioned medium from human islets exposed to a type 2 diabetic milieu could induce increased migration of monocytes and neutrophils. This migration was blocked by IL-8 neutralization, and IL-8 was localized to the human pancreatic alpha-cell. Therefore, islet-derived inflammatory factors are regulated by a type 2 diabetic milieu and may contribute to the macrophage infiltration of pancreatic islets that we observe in type 2 diabetes.

PURPOSE: To examine the activity profile and physical loading of elite female soccer players during match play and to study the relationship between training status and physical match performance. METHODS: Time-motion analysis and HR recordings were performed on 14 elite female soccer players during competitive matches. In addition, the players carried out a laboratory treadmill test and the Yo-Yo intermittent recovery test. RESULTS: The total distance covered during a game was 10.3 km (range: 9.7-11.3) with high-intensity running (HIR) accounting for 1.31 km (0.71-1.70). HIR was performed 125 times (72-159) for 2.3 s (2.0-2.4) on average. The average and peak HR in a game were 167 beats per minute (bpm) (152-186) and 186 (171-205), respectively, corresponding to 87% (81-93) and 97% (96-100) of HR(max). Maximal pulmonary oxygen uptake (VO2max) was 49.4 mL.min(-1).kg(-1) (43.4-56.8), and incremental treadmill test (ITT) performance was 4.49 min (3.38-5.17). The Yo-Yo test performance was 1379 m (600-1960). The total distance covered during match play did not correlate with VO2max or ITT performance but correlated with the Yo-Yo test result (r = 0.56, P < 0.05). Significant positive correlations were observed between HIR and VO2max (r = 0.81, P < 0.05), ITT (r = 0.82, P < 0.05), and Yo-Yo test performance (r = 0.76, P < 0.05). No relationship was observed between HR(max) during match play and any of the performance measures. CONCLUSION: The present study demonstrated that 1) HIR during games varies markedly between elite female soccer players, 2) all players have high HR throughout a competitive game with periods of near-maximal values, 3) the distance covered by HIR during match play is closely related to the physical capacity, and 4) the Yo-Yo intermittent recovery test can be used as an indicator of the physical match performance of elite female players.

A decrease in the number of functional insulin-producing beta-cells contributes to the pathophysiology of type 2 diabetes. Opinions diverge regarding the relative contribution of a decrease in beta-cell mass versus an intrinsic defect in the secretory machinery. Here we review the evidence that glucose, dyslipidemia, cytokines, leptin, autoimmunity, and some sulfonylureas may contribute to the maladaptation of beta-cells. With respect to these causal factors, we focus on Fas, the ATP-sensitive K+ channel, insulin receptor substrate 2, oxidative stress, nuclear factor-kappaB, endoplasmic reticulum stress, and mitochondrial dysfunction as their respective mechanisms of action. Interestingly, most of these factors are involved in inflammatory processes in addition to playing a role in both the regulation of beta-cell secretory function and cell turnover. Thus, the mechanisms regulating beta-cell proliferation, apoptosis, and function are inseparable processes.