More marked stimulation by lithium than insulin of the glycogenic
pathway in rat skeletal muscle.
F[umlaut]urnsinn, Clemens, Christoph Noe, Robert Herdlicka, Michael
Roden, Peter Nowotny, Brendan Leighton, and Werner Waldh[umlaut]ausl.
Department of Medicine III, Division of Endocrinology & Metabolism,
University of Vienna, A-1090 Vienna, Austria, and Department of
Biochemistry, University of Oxford, Oxford OX1 3QU, U.K.
APStracts 4:0112E, 1997.
Lithium's impact on glucose metabolism was compared to that of insulin
in isolated rat soleus muscle. 20 mmol/l lithium chloride induced a
4.8-fold more pronounced increment over basal glycogen synthase
activity than 10 nmol/l insulin (nmol UDP-glucose into glycogen in
synthase activity assay/g/min: lithium, +22.1+/-1.8 vs. insulin,
+4.6+/-3.9; p<0.01). In parallel, lithium was less efficient than
insulin in stimulating glucose transport (cpm 3H-2-deoxyglucose/mg/h:
lithium, +211+/-19 vs. insulin, +311+/-57; p<0.05) and lactate
release ([mu]mol/g/h: lithium, +1.0+/-0.5 vs. insulin, +3.9+/-0.5;
p<0.01), while similar increments were induced in glycogen
synthesis ([mu]mol glucose into glycogen/g/h: lithium, +3.32+/-0.43
vs. insulin, +3.46+/-0.47; n.s.). Full additivity of glycogenic
effects and divergent dependency on phosphatidylinsositol 3-kinase
activation provided further evidence for different mechanisms of
action. In muscle from insulin resistant obese Zucker rats (fa/fa),
failure of lithium to reverse deficits in glucose metabolism
suggested a primary deficit in muscle glucose uptake rather than
glycogen synthesis. Hence, lithium distinctly stimulates glycogen
synthase activity in skeletal muscle and may therefore be regarded a
candidate for the treatment of disorders associated with primary
deficits in the glycogenic pathway.
Received 2 December 1996; accepted in final form 2 May 1997.
APS Manuscript Number E592-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 11 June 1997