Basal alpha-cell up-regulation in obese insulin-resistant adolescents.
BACKGROUND
The aim of this analysis was to evaluate glucagon and c-peptide concentrations in two scenarios: euglycemic hyperinsulinemia and hyperglycemic hyperinsulinemia. We postulated that worsening obesity and insulin resistance will be reflected as an up-regulated (less suppressible) islet secretion profile.


METHODS
Eighty-two [34 obese with normal glucose tolerance (NGT), 30 obese with impaired glucose tolerance (IGT), and 18 nonobese with NGT] subjects underwent a euglycemic-hyperinsulinemic clamp (EHC) and a hyperglycemic clamp. C-peptide and glucagon were evaluated at basal and steady-state (SS) conditions.


RESULTS
Basal glucagon was significantly elevated in obese insulin-resistant and obese IGT subjects as was basal c-peptide. SS glucagon and c-peptide levels during the EHC were lower in the lean and obese insulin-sensitive subjects compared with the obese insulin-resistant subjects with NGT or IGT. Fasting glucagon was the only significant determinant (β = 0.66, P < 0.001) of SS glucagon during the EHC (R(2) = 0.57). In a longitudinal follow-up of a subsample, those who converted from normal to IGT significantly increased their fasting glucagon concentration in comparison with those who remained with NGT.


CONCLUSIONS
Islet up-regulation manifesting as basal elevated glucagon and c-peptide secretion that determines the suppressive effects of hyperinsulinemia appears early in the course of deteriorating glucose tolerance.
Weiss
Ram
R
Department of Human Metabolism and Nutrition, Braun School of Public Health, Hebrew University School of Medicine, Jerusalem, Israel. ram.weiss@ekmd.huji.ac.il
D'Adamo
Ebe
E
Santoro
Nicola
N
Hershkop
Karen
K
Caprio
Sonia
S
D000293:Adolescent; D000704:Analysis of Variance; D019540:Area Under Curve; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D005934:Glucagon / Q000097:blood; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D012044:Regression Analysis; D015854:Up-Regulation; D055815:Young Adult
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005934:Glucagon