Genetic background determines the size and structure of the endocrine pancreas

Key parameters of the endocrine pancreas, such as islet number, islet mass, beta-cell mass, and alpha-cell mass, were studied in different strains of inbred mice to investigate the impact of genetic background on the size and structure of the endocrine pancreas. Six mice from each of seven different strains of inbred mice were included in the study. For all parameters investigated, there was a pronounced interstrain variation. ANCOVA showed that only mouse strain was statistically significant as an explanatory parameter for the number of islets. Mouse strain, body weight, and pancreas mass reached statistical significance as explanatory parameters for the islet mass, with mouse strain as the most significant predictor. These data show that genetic background is the most important predictor of both the number of islets and total islet volume. We also conclude that inbred mice could be a valuable resource to identify the genes responsible for the size and structure of the endocrine pancreas.     

Intramuscular triacylglycerol in energy metabolism during exercise in humans

Intramuscular triacylglycerol (IMTG) represents an energy store that can be used during exercise, when it may contribute up to 20% of total energy turnover depending on diet, gender, and exercise type. It is important to consider how measurements of IMTG have been performed. Hormone-sensitive lipase is thought to regulate breakdown of IMTG during exercise.     

Resuscitation with 100% O2 increases cerebral injury in hypoxemic piglets

Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O2 compared with ambient air is detrimental to the cerebral tissue. We assessed cerebral injury in newborn piglets that underwent global hypoxia and subsequent resuscitation with 21 or 100% O2 by extracellular glycerol, matrix metalloproteinase (MMP) expression levels, and oxidative stress. Extracellular glycerol was sampled by cerebral microdialysis. MMP levels were analyzed in cerebral tissue by gelatin zymography, broad matrix degrading capacity, and real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity assay. Extracellular glycerol increased 50% after resuscitation with 100% O2 compared with 21% O2. Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p=0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O(2) (p=0.003) and 100% O2 (p=0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O2 as compared with 21% O2 (p < 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O2 were considerably reduced compared with both baseline (p=0.001) and piglets that were resuscitated with 21% O2 (p=0.001). In conclusion, our data show increased MMP-2 activity at both gene and protein levels, accompanied with cerebral leakage of glycerol, presumably triggered by augmented oxidative stress. Our findings suggest that resuscitation of asphyxiated piglets with 100% O2 is detrimental to the piglet brain compared with resuscitation with 21% O2.     

Immuno-endocrine and metabolic responses to long distance ski racing in world-class male and female cross-country skiers

The purpose of this study was to characterize the extent of immune, endocrine, substrate and metabolic changes during a long-distance cross-country ski race in extremely well-trained athletes and evaluate if the blood perturbations would indicate signs of health risk. Ten male (M) and six female (F) national team skiers were investigated as they followed their usual routines of race preparations. Blood samples were drawn before and immediately after a World Cup 50-km M and 30-km F ski race with a mean finish time of 142 and 104 min, respectively. Hemoglobin, electrolytes, and C-reactive protein remained unchanged for both M and F. Serum testosterone remained unchanged in M, but doubled in F. Significant increases were observed in concentrations of granulocytes (F: 5 x, M: 5 x), natural killer cells (F: 2 x, M: 1.5 x), adrenaline (F: 12 x, M:10 x), noradrenaline (F: 7 x, M:5 x), growth hormone (F: 30 x, M: 2 x), cortisol (F: 1.5 x, M:2 x), glucose (F: 2 x, M:1.5 x), creatine kinase (F: 2 x, M:2 x), uric acid (F: 1.5 x, M: 1.5 x) and non-organic phosphate (F:2 x, M:2 x), while insulin concentration decreased (F: 0.5x, M: 0.8 x). Free fatty acid (FFA) concentration increased (F:2 x, M: 3 x). In conclusion, we observed substantial changes in several immuno-endocrine, substrate and metabolic measurements after long distance cross-country ski racing and suggest that some of these marked changes may reflect the large amount of muscle mass involved during skiing.     

Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction

The mechanisms that mediate the tightly controlled production and clearance of glucose during muscular work are unclear, and it has been suggested that an unidentified "work factor" exists that influences the contraction-induced increase in endogenous glucose production (EGP). The cytokine interleukin (IL)-6 is released from skeletal muscle during contraction. Here we show that IL-6 contributes to the contraction-induced increase in EGP. Six men performed 2 h of bicycle exercise on three separate occasions, at a relatively high intensity (HI) or at a low intensity with (LO + IL-6) or without (LO) an infusion of recombinant human IL-6 that matched the circulating concentration of IL-6 seen in HI exercise. The stable isotope 6,6 (2)H(2) glucose was infused to calculate EGP (rate of glucose appearance [R(a)]), whole-body glucose disposal (rate of glucose disappearance [R(d)]), and metabolic clearance rate (MCR) of glucose. Glucose R(a), R(d), and MCR were higher (P < 0.05) at HI than at LO. Throughout exercise at LO + IL-6, glucose R(a) and R(d) were higher (P < 0.05) than LO, even though the exercise intensity was identical. In addition, MCR was higher (P < 0.05) at LO + IL-6 than at LO at 90 min. Insulin, glucagon, epinephrine, norepinephrine, cortisol, and growth hormone were identical when comparing LO + IL-6 with LO. These data suggest that IL-6 influences glucose homeostasis during exercise. Our results provide potential new insights into factors that mediate glucose production and disposal and implicates IL-6 in the so-called "work factor."     

Antipolymer antibodies in Danish women with silicone breast implants

OBJECTIVE: To use a new immunologic assay to evaluate antipolymer antibody (APA) levels among women with silicone breast implants (SBIs). METHODS: Women (n = 186) were identified through Danish population-based registers and categorized into six groups defined by prior breast surgery (silicone breast implantation/breast reduction/no breast surgery) and by the presence or absence of a prior hospital diagnosis of soft-tissue rheumatism (muscular rheumatism, ICD-8 codes 717.90 and 717.99). The women underwent blood tests, including an APA test, a clinical examination, and an interview focusing on rheumatic complaints. Blood samples were tested blindly. The severity of rheumatic symptoms/signs was scored from 1 (none) to 5 (severe) based on the clinical examination and interview. RESULTS: Women with SBIs did not have higher levels of APA than women without SBIs. The majority of women with SBIs had mild rheumatic complaints, and the severity of their symptoms was not related to APA levels. Among women who had previously been hospitalized because of soft-tissue rheumatism, there were more fibromyalgia cases, and their symptoms were more severe compared with those women without prior soft-tissue rheumatism; however, APA levels were not higher among these women. There was a significant difference in APA measurements resulting from between-kit variation (p less 0.01). CONCLUSIONS: Our data did not demonstrate higher APA levels among women with SBIs compared with controls. The large variation observed between the individual plates in the APA test should be evaluated in future studies.     

Postexercise muscle triacylglycerol and glycogen metabolism in obese insulin-resistant zucker rats

OBJECTIVE: To determine the impact of insulin resistance and obesity on muscle triacylglycerol (IMTG) and glycogen metabolism during and after prolonged exercise. RESEARCH METHODS AND PROCEDURES: Female lean (fa/?; N = 40, ZL) and obese insulin-resistant (fa/fa; N = 40, ZO) Zucker rats performed an acute bout of swimming exercise (8 times for 30 minutes) followed by 6 hours of carbohydrate supplementation (CHO) or fasting (FAST). IMTG and glycogen were measured in the extensor digitorum longus (EDL) and red vastus lateralis (RVL) muscles. RESULTS: Despite resting IMTG content being 4-fold higher in ZO compared with ZL rats, IMTG levels were unchanged in either EDL or RVL muscles immediately after exercise. Resting glycogen concentration in EDL and RVL muscles was similar between genotypes, with exercise resulting in glycogen use in both muscles from ZL rats (approximately 85%, p < 0.05). However, in ZO rats, there was a much smaller decrease in postexercise glycogen content in both EDL and RVL muscles (approximately 30%). During postexercise recovery, there was a decrease in EDL muscle levels of IMTG in ZL rats supplemented with CHO after 30 and 360 minutes (p < 0.05). In contrast, IMTG content was increased above resting levels in RVL muscles of ZO rats fasted for 360 minutes. Six hours of CHO refeeding restored glycogen content to resting levels in both muscles in ZL rats. However, after 6 hours of FAST in ZO animals, RVL muscle glycogen content was still lower than resting levels (p < 0.05). At this time, IMTG levels were elevated above basal (p < 0.05). DISCUSSION: In both healthy and insulin-resistant skeletal muscle, there was negligible net IMTG degradation after a single bout of prolonged exercise. However, during postexercise recovery, there was differential metabolism of IMTG between phenotypes.