Stimulation of Glucose Metabolism in Brown Adipose Tissue by Addition of Insulin in Vitro
Stanley E. Shackney 1 and Cliffe D. Joel 1
From the
1 From the Department of Biological Chemistry, Harvard Medical School, and the Massachusetts Mental Health Center, Boston, Massachusetts 02115
The effects of insulin added in vitro on the metabolic fates of uniformly labeled glucose-14C in slices of rat interscapular brown adipose tissue were studied.
Insulin strongly stimulated glucose uptake, lactate production, oxygen consumption, total carbon dioxide production, and conversion of uniformly labeled glucose-14C into fatty acids, glyceride-glycerol, carbon dioxide, and total lipids. Fatty acid synthesis from extracellular glucose was particularly sensitive to insulin and was stimulated approximately 60-fold by addition of this hormone.
The insulin concentration required for half-maximal stimulation of net gas exchange was in the general range of estimated plasma insulin concentrations.
The rate of fatty acid synthesis from extracellular glucose by brown adipose tissue slices under maximal stimulation by insulin was found to be lower by several-fold than that of white adipose tissue of similar rats, when the comparison is made per unit weight of lipid-free dry tissue. It is suggested that this may at least partially account for the relatively low content of stored triglycerides which characterizes brown adipose tissue in vivo.
Although the stimulation of oxygen consumption in white adipose tissue by insulin has recently been quantitatively accounted for in terms of the necessity to reoxidize excess pyridine nucleotides generated during the passage of glucose through the pentose phosphate shunt and conversion of glucose to fatty acids, this explanation does not in its simplest form account adequately for the stimulation of oxygen consumption in brown adipose tissue by insulin.
Certain apparent advantages are enumerated which seem to make attractive the use of brown adipose tissue for further study of the primary chemical mechanism of action of insulin.
Submitted on April 20, 1966