ABSTRACT
The dynamic response to insulin is highly potentiated after meal ingestion, and this meal-induced insulin sensitization (MIS) in healthy subjects is dependent on cholinergic mechanisms. The main objective of this study was to test the hypothesis that the reduced response to insulin observed in moderately overweight subjects, in comparison with control lean subjects, is due to MIS impairment and not to a reduction in the direct hypoglycemic action of insulin. Both lean and overweight male subjects were recruited. Insulin sensitivity (IS) was assessed by the rapid insulin sensitivity test (RIST) performed after a 24 h fast, as well as after a standardized meal. Fasting glucose disposal was similar between lean and overweight subjects. Following the meal, glucose disposal increased more extensively in lean than overweight subjects. The insulin profiles, in both fasted and fed states, were superimposable, suggesting that the absence of a factor other than insulin is responsible for the decreased postprandial insulin sensitivity observed in overweight subjects. Our data suggest that in overweight subjects, MIS contribution is decreased, which is responsible for the postprandial impaired IS observed and is suggested to be the cause, not effect, of mild adiposity.
Subject(s)
Fasting/physiology , Insulin Resistance/physiology , Overweight/physiopathology , Postprandial Period/physiology , Adult , Blood Glucose/metabolism , C-Peptide/metabolism , Energy Metabolism , Fasting/blood , Glucose/metabolism , Humans , Insulin/blood , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/physiology , Male , Overweight/blood , Overweight/metabolismABSTRACT
In animal studies, the whole-body glucose disposal effect of insulin is low in the fasted state or after atropine infusion, but doubles after a meal, consistent with the hepatic insulin-sensitizing substance (HISS) hypothesis. We tested how a standardized test meal and atropine affected the dynamic response to insulin in humans. Insulin sensitivity was assessed in healthy male subjects (aged 28.9 +/- 1.9 years, body mass index 23.3 +/- 0.8 kg.m-2) by using the rapid insulin sensitivity test (RIST), which is a transient euglycemic clamp. After a 24-hour fasting period, dynamic insulin sensitivity was assessed and then repeated 100 min after the test meal. In a second protocol, the volunteers were fed the standardized test meal and intravenous atropine (0.5 mg) or saline (control group) was administered 50 min before insulin sensitivity assessment. Insulin sensitivity increased in the fed state (232.1% +/- 46.3%, n = 7) in comparison with the 24-hour fasted state. In the atropine protocol, the drug partially blocked (56.5% +/- 11.6%, n = 6) insulin sensitivity. In humans, feeding resulted in increased insulin sensitivity. The low dose of atropine in humans lead to a partial HISS-dependent decrease in insulin sensitivity. Meal-induced insulin sensitization occured in humans by a similar mechanism as that reported in other species. The sensitization process was regulated by a cholinergic 'feeding signal.'
Subject(s)
Eating , Insulin/metabolism , Parasympathetic Nervous System/physiology , Adult , Atropine/pharmacology , Glucose Clamp Technique , Humans , Insulin Secretion , Male , Parasympatholytics/pharmacologyABSTRACT
The objective of this study was to develop a Rapid Insulin Sensitivity Test (RIST) in humans, a test already used in animal studies. Insulin sensitivity was assessed using a rapid modified euglycemic clamp, the RIST. In this test, glucose disposition was determined after an intravenous (i.v.) bolus (50mU/kg bw administered over 30 seconds) of insulin, before and after feeding a standardized test meal, in healthy male subjects (aged 27.8 +/- 2.4 years, BMI 23.5 +/- 1.2 kg/m2). The RIST uses as the index of insulin sensitivity, the total amount of glucose required to be infused to maintain euglycemia during insulin action following an i.v. bolus of insulin. During the RIST, glucose levels are determined at 2-min intervals in order to clamp the glycemia at baseline values. Following a 24 hr fasting period, the RIST index was 225.6 +/- 25.1 mg glucose/kg bw. The volunteers were then fed a standardized test meal, a new stable glucose level was obtained 100 min after the meal, and a second RIST was performed. The glucose requirement (RIST index) increased to 647.9 +/- 73.5 mg glucose/kg bw following the standardized test meal (n = 5, p < 0.001). This report describes a new technique to evaluate insulin sensitivity in healthy humans. The RIST is a powerful research tool to assess the glucose utilization action of an insulin bolus in fasted and fed states both evaluated in the same day.
