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Context Hyperglucagonemia is observed in individuals with obesity and contributes to the hyperglycemia of patients with type 2 diabetes. Hyperglucagonemia may develop due to steatosis-induced hepatic glucagon resistance resulting in impaired hepatic amino acid turnover and ensuing elevations of circulating glucagonotropic amino acids. Objective We evaluated whether glucagon resistance could be induced in healthy individuals by a hypercaloric diet intervention designed to increase hepatic fat content. Methods We recruited 20 healthy male individuals to follow a hypercaloric diet and a sedentary lifestyle for 2 weeks. Amino acid concentrations in response to infusion of glucagon were assessed during a pancreatic clamp with somatostatin and basal insulin. The reversibility of any metabolic changes was assessed 8 weeks after the intervention. Hepatic steatosis was assessed by magnetic resonance spectroscopy. Results The intervention led to increased hepatic fat content (382% [206%; 705%], P <.01). Glucagon infusion led to a decrease in the concentration of total amino acids on all experimental days, but the percentage change in total amino acids was reduced (−2.5% ± 0.5% vs −0.2% ± 0.7%, P =.015) and the average slope of the decline in the total amino acid concentration was less steep (−2.0 ± 1.2 vs −1.2 ± 0.3 μM/min, P =.016) after the intervention compared to baseline. The changes were normalized at follow-up. Conclusion Our results indicate that short-term unhealthy behavior, which increases hepatic fat content, causes a reversible resistance to the effect of glucagon on amino acid concentrations in healthy individuals, which may explain the hyperglucagonemia associated with obesity and diabetes. [ABSTRACT FROM AUTHOR]

Infusion of oxyntomodulin and the separate and combined infusion of GLP-1 and glucagon inhibited food intake similarly in healthy individuals, with no superior effect of combining GLP-1 and glucagon. We confirm the inhibitory effects of oxyntomodulin and GLP-1, respectively, on GE and appetite scores observed previously, but by adding glucagon to the infusion of GLP-1 we found no additive effects. Unexpectedly, glucagon alone had no effect on GE and appetite scores, but inhibited food intake to the same extent as oxyntomodulin, GLP-1 and GLP-1 + glucagon. Both the GLP-1, oxyntomodulin and GLP-1 + glucagon infusions appeared to increase O 2 compared to saline but this observation is most likely confounded by a residual meal-induced thermogenesis because the calorimetry was performed relatively soon after the paracetamol peak indicating that a considerable volume still resided in the stomach and a high rate of nutrient absorption probably was still going on compared to the saline infusion. Flint et al previously concluded from a protocol very similar to ours using GLP-1 infusions, that the observed increases in energy expenditure most likely were linked to the meal. In contrast, we observed no significant changes in O 2 from baseline in any of the experiments in our study. The lack of a clear effect on O 2 is in contrast to recently reported findings regarding infusions of glucagon and GLP-1. But the dose of glucagon used in that particular study was more than 15-fold higher than ours and associated with large changes in glucose and insulin levels. Such levels are likely to influence REE and offer an explanation of the reported additive effect of combinations of GLP-1 and glucagon. Our conclusion is consistent with recent findings showing no increases after short-term native GLP-1 infusions. Long-term treatment with the GLP-1 analogue liraglutide using 24 h chamber calorimetry has so far shown no differences in energy expenditure following the treatment. Surprisingly, the infusion of glucagon did not change gastric emptying. This finding is controversial since glucagon previously has been used to inhibit bowel motility. However, the doses used to inhibit bowel motility were more than 3,000-fold higher than the dose used in the present study and as mentioned above, such doses might activate the GLP-1 receptor pathway. Interestingly, the glucagon infusion did result in decreased food intake to the same extent as the other peptide infusions despite having no impact on gastric emptying and appetite scores. We found a mean 180 kcal (120 g) difference in food intake following infusions of all the peptides compared to saline. This would roughly sum up to a body weight loss of 402 g of fat per week, which is in the range of what previously has been found in overweight and obese humans with the injection of oxyntomodulin.

Introduction: Night duties in surgical wards can be demanding physically and mentally. Staffing the emergency room, performing emergency operations and taking care of the admitted patients are only few of surgeons' tasks during these busy duties. Night duties can have different effects on the following day/days tasks, limiting some of the leisure activities and maybe life quality. Literature search, however, shows few studies about the subject. The aim of this study was twofold: to study the effects of night duties on the general health of surgeons and to classify duties according to these effects., Methods: Retrospective study based on modified Short Form Survey (SF)-12. Questionnaire forms were sent to all surgeons in the surgical department at Hvidovre Hospital., Results: The questionnaire forms were sent to 64 surgeons and 38 answered (59.4%). The highest response rate was in the residents group (71.9%: 23/32), senior residents group (70%: 7/10) and the lowest rate in consultants group (36.4%: 8/22)., Conclusion: Night duties have no significant effect on surgeons' general health. There is a trend, however, that these duties have an effect on hard physical and/or mental activities in the following day especially for female surgeons., Funding: not relevant., Trial Registration: not relevant.