Effects of amylin on glucose metabolism and glycogenolysis in vivo and in vitro.
The effects of amylin on glucose metabolism and glycogenolysis were examined in vivo and in vitro. Eighteen-hour-fasted rats were infused with 5 nmol.kg-1.min-1 amylin and [3-3H]glucose for 120 min. Blood glucose levels increased an average of 45% during the infusion. Glucose turnover measurements indicated that the overall rate of glucose appearance (Ra) did not change, but the metabolic clearance rate of glucose was decreased by 42%. Samples of liver, gastrocnemius, and soleus muscles were freeze-clamped at the end of the infusion period and analyzed for glycogen and glucose 6-phosphate levels. Glycogen levels were decreased in all tissue samples, whereas glucose 6-phosphate was elevated in gastrocnemius and soleus muscles. Isolated soleus muscles were incubated in vitro with 200 microU/ml of insulin and 1, 10, or 100 nM amylin. Amylin treatment had no effect on 3-O-methyl-D-glucose transport; however, 2-deoxy-D-glucose uptake was inhibited by 33 or 48% at 10 or 100 nM amylin, respectively. Glycogen levels were also decreased after treatment with 10 and 100 nM amylin. Glucose 6-phosphate levels were not affected by amylin treatment in the presence of insulin but were increased nearly twofold in its absence. The data suggest that amylin stimulates glycogenolysis and inhibits glucose uptake both in vivo and in vitro and that the inhibition of glucose uptake is due to inhibition of glucose phosphorylation (i.e., hexokinase).
Young
D A
DA
Diabetes Department, Sandoz Research Institute, Sandoz Pharmaceuticals, East Hanover, New Jersey 07936.
Deems
R O
RO
Deacon
R W
RW
McIntosh
R H
RH
Foley
J E
JE
D019325:3-O-Methylglucose; D000682:Amyloid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D058228:Islet Amyloid Polypeptide; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000682:Amyloid; D001786:Blood Glucose; D005958:Glucosephosphates; D058228:Islet Amyloid Polypeptide; D008757:Methylglucosides; D019325:3-O-Methylglucose; D019298:Glucose-6-Phosphate; D006003:Glycogen; D003847:Deoxyglucose; D005947:Glucose