CONTEXT: 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.
CONTEXT: 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.
Authors: Ram Weiss; Sylvie Dufour; Sara E Taksali; William V Tamborlane; Kitt F Petersen; Riccardo C Bonadonna; Linda Boselli; Gina Barbetta; Karin Allen; Francis Rife; Mary Savoye; James Dziura; Robert Sherwin; Gerald I Shulman; Sonia Caprio Journal: Lancet Date: 2003-09-20 Impact factor: 79.321
Authors: C J Goodner; B C Walike; D J Koerker; J W Ensinck; A C Brown; E W Chideckel; J Palmer; L Kalnasy Journal: Science Date: 1977-01-14 Impact factor: 47.728
Authors: Andrew C Ertl; Stephnie Mann; Antoinette Richardson; Vanessa J Briscoe; Hannah B Blair; Donna B Tate; Stephen N Davis Journal: Am J Physiol Endocrinol Metab Date: 2008-07-08 Impact factor: 4.310
Authors: L G Trahair; C S Marathe; S Standfield; C K Rayner; C Feinle-Bisset; M Horowitz; K L Jones Journal: Int J Obes (Lond) Date: 2016-12-06 Impact factor: 5.095
Authors: David R Weber; Lorraine E Levitt Katz; Babette S Zemel; Paul R Gallagher; Kathryn M Murphy; Susan M Dumser; Terri H Lipman Journal: Diabetes Res Clin Pract Date: 2014-01-08 Impact factor: 5.602
Authors: P C Chandler-Laney; P B Higgins; W Granger; J Alvarez; K Casazza; J R Fernandez; C Dalla Man; C Cobelli; B A Gower Journal: Pediatr Obes Date: 2013-02-28 Impact factor: 4.000
Authors: Sara E Stinson; Anna E Jonsson; Ierai Fernández de Retana Alzola; Morten A V Lund; Christine Frithioff-Bøjsøe; Louise Aas Holm; Cilius E Fonvig; Oluf Pedersen; Lars Ängquist; Thorkild I A Sørensen; Jens J Holst; Michael Christiansen; Jens-Christian Holm; Bolette Hartmann; Torben Hansen Journal: J Clin Endocrinol Metab Date: 2022-05-17 Impact factor: 6.134
Authors: Steven E Kahn; Kieren J Mather; Silva A Arslanian; Elena Barengolts; Thomas A Buchanan; Sonia Caprio; David A Ehrmann; Tamara S Hannon; Santica Marcovina; Kristen J Nadeau; Kristina M Utzschneider; Anny H Xiang; Sharon L Edelstein Journal: Diabetes Care Date: 2021-06-15 Impact factor: 17.152
Authors: R Guardado-Mendoza; L Jimenez-Ceja; A Majluf-Cruz; S Kamath; T V Fiorentino; F Casiraghi; A O C Velazquez; R A DeFronzo; E Dick; A Davalli; F Folli Journal: Int J Obes (Lond) Date: 2012-12-11 Impact factor: 5.551
Authors: Sara F Michaliszyn; Andrea Mari; SoJung Lee; Fida Bacha; Hala Tfayli; Lama Farchoukh; Ele Ferrannini; Silva Arslanian Journal: Diabetes Date: 2014-06-19 Impact factor: 9.461