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Julia Otten Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Andreas Stomby Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
Region Jönköping County, Jönköping, Sweden

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Maria Waling Department of Food, Nutrition and Culinary Science, Umeå University, Umeå, Sweden

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Elin Chorell Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Mats Ryberg Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Michael Svensson Department of Community Medicine and Rehabilitation, Section for Sports Medicine, Umeå University, Umeå Sweden

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Jens Juul Holst NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

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Tommy Olsson Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Objective

Glucagon and amino acids may be regulated in a feedback loop called the liver-alpha-cell axis with alanine or glutamine as suggested signal molecules. We assessed this concept in individuals with type 2 diabetes in the fasting state, after ingestion of a protein-rich meal, and during weight loss. Moreover, we investigated if postprandial glucagon secretion and hepatic insulin sensitivity were related.

Methods

This is a secondary analysis of a 12-week weight-loss trial (Paleolithic diet ± exercise) in 29 individuals with type 2 diabetes. Before and after the intervention, plasma glucagon and amino acids were measured in the fasting state and during 180 min after a protein-rich mixed meal. Hepatic insulin sensitivity was measured using the hyperinsulinemic-euglycemic clamp with [6,6-2H2]glucose as a tracer.

Results

The postprandial increase of plasma glucagon was associated with the postprandial increase of alanine and several other amino acids but not glutamine. In the fasted state and after the meal, glucagon levels were negatively correlated with hepatic insulin sensitivity (rS = −0.51/r = −0.58, respectively; both P < 0.05). Improved hepatic insulin sensitivity with weight loss was correlated with decreased postprandial glucagon response (r = −0.78; P < 0.001).

Conclusions

Several amino acids, notably alanine, but not glutamine could be key signals to the alpha cell to increase glucagon secretion. Amino acids may be part of a feedback mechanism as glucagon increases endogenous glucose production and ureagenesis in the liver. Moreover, postprandial glucagon secretion seems to be tightly related to hepatic insulin sensitivity.

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Marcus Imamovic Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Nils Bäcklund Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Staffan Lundstedt Department of Medical Biosciences, Umeå University, Umeå, Sweden

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Göran Brattsand Department of Medical Biosciences, Umeå University, Umeå, Sweden

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Elisabeth Aardal Department of Clinical Chemistry and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden

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Tommy Olsson Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Per Dahlqvist Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Objective

To determine the effects of liquorice consumption, topical hydrocortisone, and blood contamination on salivary cortisol and cortisone concentrations.

Design and methods

Thirty healthy volunteers were randomized to a low, medium, or high dose of liquorice. Late-night saliva samples were collected using a Salivette® collection device at baseline, during 1 week of daily liquorice consumption, and during 4 weeks' washout. Saliva sampling was also performed before and after the application of topical hydrocortisone on the skin. Furthermore, in a subgroup (n  = 16), saliva and venous blood were collected from each individual and mixed to achieve graded blood contamination in saliva. Salivary cortisol and cortisone were analyzed with liquid chromatography-tandem mass spectrometry.

Results

Significant increases in salivary cortisol concentrations were observed during medium- (+49%) and high-dose (+97%) liquorice intake, which returned to baseline 4 days after liquorice withdrawal. Topical hydrocortisone on fingers holding the collection swab increased salivary cortisol concentrations >1000-fold with concomitant pronounced elevation of the cortisol:cortisone ratio. Salivary cortisol increased significantly after contamination with blood ≥0.5%. Visual examination could safely detect these samples. Salivary cortisone concentrations were unaffected by liquorice consumption and blood contamination, and only marginally affected by topical hydrocortisone.

Conclusion

Liquorice, topical hydrocortisone, and blood contamination may all cause elevated salivary cortisol concentrations. Improved sampling instructions and visual examination of the sample may minimize these risks. Salivary cortisone is essentially unaffected by the different preanalytical confounders and may be used as a first-line screening test for Cushing's syndrome.

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Melony C Fortuin-de Smidt Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa

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Amy E Mendham Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa

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Jon Hauksson Department of Radiation Sciences, Radiation Physics and Biomedical Engineering, Umea University, Umea, Sweden

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Ali Alhamud Department of Human Biology, MRC/UCT Medical Imaging Research Unit, University of Cape Town, Cape Town, South Africa
The Modern Pioneer Center and ArSMRM for MRI Training and Development, Tripoli, Libya

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Darko Stefanovski Department of Clinical Studies, New Bolton Centre, University of Pennsylvania School of Veterinary Medicine, Kennett Square, Pennsylvania, USA

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Olah Hakim Department of Diabetes, Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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Jeroen Swart Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa

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Louise M Goff Department of Diabetes, Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK

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Steven E Kahn Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington, USA

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Tommy Olsson Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden

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Julia H Goedecke Division of Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town, South Africa
Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa

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The role of ectopic fat, insulin secretion and clearance in the preservation ofβ-cell function in black African women with obesity who typically present with hyperinsulinaemia is not clear. We aim to examine the associations between disposition index (DI, an estimate of β-cell function), insulin secretion and clearance and ectopic fat deposition. This is a cross-sectional study of 43 black South African women (age 20–35 years) with obesity (BMI 30–40 kg/m2) and without type 2 diabetes that measured the following: DI, insulin sensitivity (SI), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently sampled i.v. glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal s.c. adipose tissue (aSAT) volume (MRI), intra-myocellular (IMCL) and extra-myocellular fat content (EMCL) (magnetic resonance spectroscopy). DI correlated positively with peripheral insulin clearance (β 55.80, P = 0.002). Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (P = 0.033) and lower hepatic insulin extraction (P = 0.022) were associated with lower VAT, independent from SI, rather than with ectopic fat. In conclusion, peripheral insulin clearance emerged as an important correlate of DI. However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, is associated with both lower insulin secretion and higher hepatic insulin extraction. Prevention of VAT accumulation in young black African women should, therefore, be an important target for beta cell preservation.

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