AJP - Endocrinology and Metabolism, Vol 263, Issue 4 E646-E653, Copyright © 1992 by American Physiological Society

ARTICLES

Role of FFA-glucose cycle in glucoregulation during exercise in total absence of insulin

K. Yamatani, Z. Q. Shi, A. Giacca, R. Gupta, S. Fisher, H. L. Lickley and M. Vranic
Department of Physiology, University of Toronto, Women's College Hospital, Ontario, Canada.

Muscle contraction in vitro increases glucose uptake (GU), independent of insulin, but in vivo, the exercise-induced increase in GU is impaired in insulin-deficient diabetic dogs. We wished to determine whether, in vivo, suppression of the free fatty acid (FFA)-glucose cycle with methylpalmoxirate (MP, inhibitor of FFA oxidation) alone or combined with propranolol (PRO, beta-blocker) could improve GU during exercise in the absence of insulin. We performed four groups of exercise experiments (6 km/h, 10% slope) in depancreatized insulin-deprived dogs: 1) control (n = 6); 2) MP treated (5 oral doses of 10 mg/kg, twice daily, n = 6); 3) treated with MP+octanoate (OCT; oxidation unaffected by MP, 27 mumol.kg-1.min-1 iv during exercise; n = 5); and 4) MP+PRO treated (5 micrograms.kg-1.min-1 iv during exercise, n = 6). MP abolished ketosis (inhibition of hepatic FFA oxidation), decreased basal glucose production (GP), and increased metabolic clearance of glucose (MCR). During exercise, MP attenuated the increment in GP (P < 0.01), which was reversed by OCT. MP did not affect the exercise-induced increase in GU and MCR. With MP+PRO, FFAs decreased and lactate did not rise during exercise. GP was not further suppressed, but GU and MCR were increased (P < 0.01) to 89 and 31% of normal, respectively. In insulin-deprived depancreatized dogs, glucose cycling was increased to a greater extent than GP, as in type II diabetes. By the end of exercise, glucose cycling increased (P < 0.05), but to a similar extent as GP.(ABSTRACT TRUNCATED AT 250 WORDS)

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