Defective insulin action on protein and glucose metabolism during chronic hyperinsulinemia in subjects with benign insulinoma.
The ability of chronic endogenous hyperinsulinemia to induce a resistance to insulin action on protein and glucose metabolism was studied in 10 subjects affected by a benign (functioning) insulinoma and 18 healthy subjects by means of infusions of [1-(14)C]leucine and [3-(3)H] glucose. The insulinoma subjects were divided into two groups with moderate (139 +/- 12 pmol/l) (n = 5) and marked (438 +/- 42 pmol/l) (n = 5) hyperinsulinemia and were studied during a euglycemic dextrose infusion. Control subjects were studied postabsorptively and during a low-dose (0.3 mU.kg-1.min-1) (n = 3) and a high-dose (1 mU.kg-1.min-1) (n = 15) euglycemic insulin clamp to match peripheral insulin concentrations with those of insulinoma subjects. In insulinoma subjects there was no correlation among plasma insulin concentration and leucine concentration (r = 0.05), endogenous leucine flux (r = 0.44), hepatic glucose production (r = 0.47), and glucose uptake (r = 0.05). Insulinoma subjects with marked hyperinsulinemia demonstrated a defective suppression of leucine concentrations (100 +/- 11 vs. 65 +/- 5 mumol/l, P < 0.01), endogenous leucine flux (50.1 +/- 6.3 vs. 27.1 +/- 0.9 mumol.m-2.min-1, P < 0.01), and hepatic glucose production (5.4 +/- 2.0 vs. 0.6 +/- 0.6 mumol.kg-1.min-1, P < 0.05), and a defective stimulation of glucose uptake (13.5 +/- 1.6 vs. 41.1 +/- 2.8 mumol.kg-1.min-1, P < 0.001) with respect to normal subjects at a comparable degree of hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Battezzati
A
A
Division of Endocrinology-Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Terruzzi
I
I
Perseghin
G
G
Bianchi
E
E
Di Carlo
V
V
Pozza
G
G
Luzi
L
L
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002908:Chronic Disease; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007340:Insulinoma / Q000097:blood / Q000378:metabolism*; D007651:Keto Acids / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D014316:Tritium
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D007651:Keto Acids; D011506:Proteins; D014316:Tritium; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D005947:Glucose