We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Basal alpha-cell up-regulation in obese insulin-resistant adolescents.
- Authors
Weiss, Ram; D'Adamo, Ebe; Santoro, Nicola; Hershkop, Karen; Caprio, Sonia
- Abstract
<bold>Context: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
ANALYSIS of variance; BIOCHEMISTRY; BLOOD sugar; C-peptide; COMPARATIVE studies; GLUCAGON; INSULIN; INSULIN resistance; ISLANDS of Langerhans; PHENOMENOLOGY; RESEARCH methodology; MEDICAL cooperation; OBESITY; PHARMACOKINETICS; REGRESSION analysis; RESEARCH; EVALUATION research; GLUCOSE clamp technique
- Publication
Journal of Clinical Endocrinology & Metabolism, 2011, Vol 96, Issue 1, p91
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2010-1275