Effects of physiological hyperinsulinemia on counterregulatory response to prolonged hypoglycemia in normal humans.
To test the hypothesis that differing physiological insulin levels can modify the counter-regulatory response to prolonged hypoglycemia, experiments were carried out in 10 healthy male subjects. Insulin was infused subcutaneously for 8 h in two separate randomized protocols, so that steady-state levels of 132 +/- 6 pM (low) and 402 +/- 18 pM (high) were obtained. The fall in plasma glucose was controlled by the glucose-clamp technique. Plasma glucose fell slowly and similarly in both groups, reaching an identical steady-state (final 120 min of each study) level of 3.4 +/- 0.1 mM. Steady-state plasma epinephrine (2.5 +/- 0.4 vs. 1.5 +/- 0.2 nM) and norepinephrine (1.5 +/- 0.2 vs. 1.1 +/- 0.1 nM) were significantly (P < 0.05) greater during high- compared with low-dose insulin infusions. Plasma glucagon was reduced during high compared with low infusions (104 +/- 9 vs. 150 +/- 19 ng/l, P < 0.05). Growth hormone, cortisol, and pancreatic polypeptide increased significantly but were not different during the two insulin infusions. Hepatic glucose production (HGP) was equal during the steady-state period (8.4 +/- 1.0 mumol.kg-1.min-1) of each infusion. Blood lactate levels (1,255 +/- 73 vs. 788 +/- 69 mumol/l, P < 0.02) were increased in high compared with low, but nonesterified fatty acid (205 +/- 43 vs. 579 +/- 65 mumol/l) and 3-hydroxybutyrate (40 +/- 36 vs. 159 +/- 51 mumol/l) were reduced (P < 0.002) during the high-compared with low-dose infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
Davis
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Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Shavers
C
C
Collins
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L
Cherrington
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AD
Price
L
L
Hedstrom
C
C
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002319:Cardiovascular System / Q000503:physiopathology; D005947:Glucose / Q000096:biosynthesis; D015309:Glucose Clamp Technique; D006728:Hormones / Q000097:blood*; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications*; D007003:Hypoglycemia / Q000150:complications* / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male
D001786:Blood Glucose; D002096:C-Peptide; D006728:Hormones; D007328:Insulin; D005947:Glucose