Hyperamylinemia, hyperinsulinemia, and insulin resistance in genetically obese LA/N-cp rats.
The experimental evidence supporting a direct role for hyperinsulinemia as a cause of insulin resistance remains equivocal. Amylin, an islet beta-cell peptide cosecreted with insulin in response to nutrient stimuli, causes insulin resistance when infused into intact animals or applied to isolated skeletal muscles. We compared measures of amylin and insulin gene expression between control and genetically obese, insulin-resistant Lister Albany/NIH-(LA/N-cp) rats. Pancreatic amylin messenger RNA levels were increased 7.8 +/- 0.7-fold (mean +/- SEM), and plasma amylin-like immunoreactive material was increased 10.9 +/- 1.1-fold (LA/N-lean, 14 +/- 4 pM; LA/N-cp, 153 +/- 16 pM; p less than 0.0001) in obese rats. Pancreatic insulin I mRNA levels were increased 7.4 +/- 0.5-fold, and plasma insulin levels 20.0 +/- 5.0-fold, in these rats (LA/N-lean, 308 +/- 84 pM; LA/N-cp 6,120 +/- 1,540 pM; p less than 0.0001). The EC50 for insulin-stimulated incorporation of glucose into glycogen was about fourfold higher in muscles isolated from obese rats. The present results, coupled with previous observations, support the hypothesis that hyperamylinemia, rather than hyperinsulinemia per se, could have directly caused the insulin resistance in the obese LA/N-cp rats. Hyperamylinemia needs to be considered in future experimental studies probing the relation between hyperinsulinemia and insulin resistance.
Huang
H J
HJ
Amylin Corporation, San Diego, Calif.
Young
A A
AA
Koda
J E
JE
Tulp
O L
OL
Johnson
M J
MJ
Cooper
G J
GJ
D000682:Amyloid / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D006946:Hyperinsulinism / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D058228:Islet Amyloid Polypeptide; D009132:Muscles / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D012333:RNA, Messenger; D006003:Glycogen