Context: Abnormal glucagon concentrations contribute to hyperglycemia, but the mechanisms of α-cell dysfunction in prediabetes are unclear. Objective: We sought to determine the relative contributions of insulin secretion and action to α-cell dysfunction in nondiabetic participants across the spectrum of glucose tolerance. Design: This was a cross-sectional study. A subset of participants (n = 120) was studied in the presence and absence of free fatty acid (FFA) elevation, achieved by infusion of Intralipid (Baxter Healthcare, Deerfield, IL) plus heparin, to cause insulin resistance. Setting: An inpatient clinical research unit at an academic medical center. Participants: A total of 310 nondiabetic persons participated in this study. Interventions: Participants underwent a seven-sample oral glucose tolerance test. Subsequently, 120 participants were studied on two occasions. On one day, infusion of Intralipid plus heparin raised FFA. On the other day, participants received glycerol as a control. Main Outcome Measure(s): We examined the relationship of glucagon concentration with indices of insulin action after adjusting for the effects of age, sex, and weight. Subsequently, we sought to determine whether an acute decrease in insulin action, produced by FFA elevation, altered glucagon concentrations in nondiabetic participants. Results: Fasting glucagon concentrations correlated positively with fasting insulin and C-peptide concentrations and inversely with insulin action. Fasting glucagon was not associated with any index of β-cell function in response to an oral challenge. As expected, FFA elevation decreased insulin action and also raised glucagon concentrations. Conclusions: In nondiabetic participants, glucagon secretion was altered by changes in insulin action.
Context: Abnormal glucagon concentrations contribute to hyperglycemia, but the mechanisms of α-cell dysfunction in prediabetes are unclear. Objective: We sought to determine the relative contributions of insulin secretion and action to α-cell dysfunction in nondiabetic participants across the spectrum of glucose tolerance. Design: This was a cross-sectional study. A subset of participants (n = 120) was studied in the presence and absence of free fatty acid (FFA) elevation, achieved by infusion of Intralipid (Baxter Healthcare, Deerfield, IL) plus heparin, to cause insulin resistance. Setting: An inpatient clinical research unit at an academic medical center. Participants: A total of 310 nondiabetic persons participated in this study. Interventions: Participants underwent a seven-sample oral glucose tolerance test. Subsequently, 120 participants were studied on two occasions. On one day, infusion of Intralipid plus heparin raised FFA. On the other day, participants received glycerol as a control. Main Outcome Measure(s): We examined the relationship of glucagon concentration with indices of insulin action after adjusting for the effects of age, sex, and weight. Subsequently, we sought to determine whether an acute decrease in insulin action, produced by FFA elevation, altered glucagon concentrations in nondiabetic participants. Results: Fasting glucagon concentrations correlated positively with fasting insulin and C-peptide concentrations and inversely with insulin action. Fasting glucagon was not associated with any index of β-cell function in response to an oral challenge. As expected, FFA elevation decreased insulin action and also raised glucagon concentrations. Conclusions: In nondiabetic participants, glucagon secretion was altered by changes in insulin action.
Authors: Young Lee; Eric D Berglund; Xinxin Yu; May-Yun Wang; Matthew R Evans; Philipp E Scherer; William L Holland; Maureen J Charron; Michael G Roth; Roger H Unger Journal: Proc Natl Acad Sci U S A Date: 2014-08-25 Impact factor: 11.205
Authors: Chiara Dalla Man; Marco Campioni; Kenneth S Polonsky; Rita Basu; Robert A Rizza; Gianna Toffolo; Claudio Cobelli Journal: Diabetes Date: 2005-11 Impact factor: 9.461
Authors: Kirsten Vollmer; Jens J Holst; Birgit Baller; Mark Ellrichmann; Michael A Nauck; Wolfgang E Schmidt; Juris J Meier Journal: Diabetes Date: 2007-12-05 Impact factor: 9.461
Authors: Jon D Adams; Aoife M Egan; Marcello C Laurenti; Daniel Schembri Wismayer; Kent R Bailey; Claudio Cobelli; Chiara Dalla Man; Adrian Vella Journal: Am J Physiol Endocrinol Metab Date: 2021-10-18 Impact factor: 4.310
Authors: Jacob D Kohlenberg; Marcello C Laurenti; Aoife M Egan; Daniel Schembri Wismayer; Kent R Bailey; Claudio Cobelli; Chiara Dalla Man; Adrian Vella Journal: Diabetologia Date: 2022-09-16 Impact factor: 10.460
Authors: Marcello C Laurenti; Praveer Arora; Chiara Dalla Man; James C Andrews; Robert A Rizza; Aleksey Matveyenko; Kent R Bailey; Claudio Cobelli; Adrian Vella Journal: Physiol Rep Date: 2022-07
Authors: Jon D Adams; Chiara Dalla Man; Marcello C Laurenti; M Daniela Hurtado Andrade; Claudio Cobelli; Robert A Rizza; Kent R Bailey; Adrian Vella Journal: Metabolism Date: 2020-02-08 Impact factor: 8.694
Authors: Marcello C Laurenti; Adrian Vella; Jon D Adams; Daniel J Schembri Wismayer; Aoife M Egan; Chiara Dalla Man Journal: Am J Physiol Endocrinol Metab Date: 2020-11-02 Impact factor: 4.310
Authors: John Jack L Leahy; Grazia Aleppo; Vivian A Fonseca; Satish K Garg; Irl B Hirsch; Anthony L McCall; Janet B McGill; William H Polonsky Journal: J Endocr Soc Date: 2019-10-07
Authors: J D Adams; Gerlies Treiber; Maria Daniela Hurtado; Marcello C Laurenti; Chiara Dalla Man; Claudio Cobelli; Robert A Rizza; Adrian Vella Journal: J Endocr Soc Date: 2018-11-21