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Region Jönköping County, Jönköping, 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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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.
Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa
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Non-Communicable Diseases Research Unit, South African Medical Council, Tygerberg, South Africa
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The Modern Pioneer Center and ArSMRM for MRI Training and Development, Tripoli, Libya
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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.