Human islet amyloid polypeptide at pharmacological levels inhibits insulin and phorbol ester-stimulated glucose transport in in vitro incubated human muscle strips.
Human islet amyloid polypeptide, at concentrations of 1-100 nmol/l, has been demonstrated to inhibit the insulin-stimulated increase in rat muscle glycogen content. However, at physiological concentrations (1-10 pmol/l) of islet amyloid polypeptide, no effects have been reported. We tested the effect of a wide range of concentrations of human islet amyloid polypeptide on insulin- and phorbol ester-stimulated 3-0-methylglucose transport in in vitro incubated human skeletal muscle. Muscle specimens from the quadriceps femoris muscle were obtained from 23 healthy subjects with the use of a newly-developed open muscle biopsy technique. Human islet amyloid polypeptide at a concentration of 100 nmol/l had no effect on basal glucose transport, but inhibited the stimulatory effect of a maximal insulin concentration (1000 microU/ml) by 69% (p less than 0.001). The presence of human islet amyloid polypeptide at 1, 10 and 100 nmol/l decreased the effect of 100 microU/ml of insulin on glucose transport by 61% (p less than 0.05), 78% (p less than 0.05) and 76% (p less than 0.05), respectively. Similarly, human islet amyloid polypeptide at a concentration of 10 nmol/l inhibited phorbol ester-stimulated glucose transport by 100% (p less than 0.05). The inhibitory effects of human islet amyloid polypeptide on glucose transport were present in the muscle strips despite no net changes in glycogen content. Human islet amyloid polypeptide at 10 and 100 pmol/l had no effect on the rate of insulin-stimulated glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Zierath
J R
JR
Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
Galuska
D
D
Engström
A
A
Johnson
K H
KH
Betsholtz
C
C
Westermark
P
P
Wallberg-Henriksson
H
H
D019325:3-O-Methylglucose; D000682:Amyloid / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists / Q000494:pharmacology*; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000682:Amyloid; D007328:Insulin; D007329:Insulin Antagonists; D058228:Islet Amyloid Polypeptide; D008757:Methylglucosides; D019325:3-O-Methylglucose; D013755:Tetradecanoylphorbol Acetate