Okadaic acid, insulin, and denervation effects on glucose and amino acid transport and glycogen synthesis in muscle.
Effects of okadaic acid (OKA) and calyculin A, cell-permeating specific inhibitors of phosphoprotein phosphatases-1 and -2A, were studied in isolated rat hemidiaphragms. OKA stimulated glucose transport (half-maximum = approximately 0.1 microM; maximum = approximately 1 microM) but was less effective than 6 nM insulin. Insulin and OKA effects were not additive. OKA diminished or abolished glucose transport-stimulation by insulin. System A amino acid transport was also stimulated by OKA, insulin was more effective, and preexposure to OKA inhibited insulin stimulation. Calyculin A affected both transport systems similarly to OKA. OKA did not affect basal glycogen synthesis but abolished its stimulation by insulin. Denervated muscles develop post-receptor insulin resistance. Glucose transport and glycogen synthesis were essentially unresponsive to insulin 3 days postdenervation; however, glucose transport was stimulated by OKA similarly to controls. OKA did not affect glycogen synthesis in denervated muscle except for abolishing a small insulin effect. The data suggest similar acute regulation of glucose and system A amino acid transport in muscle. Enhanced Ser/Thr phosphorylation of unidentified protein(s) stimulates both processes but inhibits their full stimulation by insulin. Postdenervation insulin resistance likely reflects impaired signal transduction.
Robinson
K A
KA
Department of Medicine, Medical University of South Carolina, Charleston 29425.
Boggs
K P
KP
Buse
M G
MG
D000596:Amino Acids / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005947:Glucose / Q000493:pharmacokinetics; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009121:Muscle Denervation; D009132:Muscles / Q000378:metabolism*; D019319:Okadaic Acid; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D000596:Amino Acids; D004988:Ethers, Cyclic; D007328:Insulin; D019319:Okadaic Acid; D006003:Glycogen; D005947:Glucose