Impaired insulin action is associated with increased glucagon concentrations in nondiabetic humans
A Sharma, RT Varghese, M Shah… - The Journal of …, 2018 - academic.oup.com
The Journal of Clinical Endocrinology & Metabolism, 2018•academic.oup.com
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 …
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 …
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.
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