Lack of acute effect of amylin (islet associated polypeptide) on insulin sensitivity during hyperinsulinaemic euglycaemic clamp in humans.
It is suggested that amylin (islet associated polypeptide), co-secreted with insulin from the pancreatic beta cells acts as a circulating hormone which opposes the action of insulin on muscle and increases hepatic glucose production. We have tested the effect of amylin in human subjects on postabsorptive glucose homeostasis and on insulin sensitivity using the euglycaemic hyperinsulinaemic clamp. The amylin used opposed insulin-mediated glucose disposal in rat soleus muscle at concentrations of 10 nmol/l. Seven subjects were studied on two occasions and infused with either amylin or placebo for 6 h, initially when postabsorptive and then during a euglycaemic hyperinsulinaemic clamp. Mean plasma amylin concentrations during the first 3 h were 2006 +/- 327 pmol/l during amylin infusion and 20 +/- 9 pmol/l during the control infusion. Amylin infusion had no effect on postabsorptive plasma concentrations of insulin (control: 32 +/- 16 vs amylin: 25 +/- 8 pmol/l) or glucose (5.1 +/- 0.1 vs 5.3 +/- 0.1 mmol/l). During the clamp, amylin concentrations were 1636 +/- 422 pmol/l when it was infused and 24 +/- 6 during control infusions. Plasma glucose and insulin concentrations were well matched during the control and amylin infusions (glucose: 4.7 +/- 0.1 vs 4.8 +/- 0.1 mmol/l; insulin: 198 +/- 37 vs 195 +/- 22 pmol/l). Exogenous glucose infusion rates were a mean of 13% lower than control values during the amylin infusion but were not statistically different (p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)
Wilding
J P
JP
Division of Endocrinology and Metabolism, Royal Postgraduate Medical School, London, United Kingdom.
Khandan-Nia
N
N
Bennet
W M
WM
Gilbey
S G
SG
Beacham
J
J
Ghatei
M A
MA
Bloom
S R
SR
D000328:Adult; D000682:Amyloid / Q000097:blood / Q000494:pharmacology*; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D008297:Male; D012016:Reference Values
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide