Reduced glucose clearance as the major determinant of
postabsorptive hyperglycemia in diabetic rats.
Wi, Jae K., Jason K. Kim, and Jang H. Youn.
Department of Physiology and Biophysics, University of Southern
California School of Medicine, Los Angeles, CA 90033
APStracts 4:0245E, 1997.
The relationships between postabsorptive glucose concentration and
hepatic glucose output (HGO) and glucose clearance were studied in
rats one day after treatment with various doses of streptozotocin
(STZ; 0, 15, 30, 40, 50, or 75 mg/kg; n=6 per dose; Study 1). Glucose
fluxes were estimated using a prolonged (6 hour) infusion of [3
-3H]glucose to ensure complete tracer equilibration at hyperglycemia.
Postabsorptive glucose was significantly increased at the high doses
of STZ (50 and 75 mg/kg; P<0.01) and was strongly correlated with
glucose clearance across all doses (r = (0.85, P< 0.001) but less
strongly with HGO (r=0.46, P<0.01). In the group treated with 50
mg/kg STZ, postabsorptive glucose was increased 2-fold, compared to
the control (i.e., zero dose) group, with no change in HGO and a 45%
decrease in glucose clearance, indicating that the hyperglycemia was
due to a decrease in glucose clearance. To understand the cellular
mechanisms of decreased glucose clearance in STZ diabetic rats,
skeletal muscle glucose clearance and intracellular glucose and
glucose 6-phosphate (G-6-P) concentrations were determined in normal
and STZ (50 mg/kg ) diabetic rats at their postabsorptive glucose
levels as well as at matched hyperglycemia (12 mM; Study 2). Glucose
clearance was significantly decreased in soleus (P<0.05) muscles of
the diabetic rats, and this was associated with significantly
decreased intracellular glucose and G-6-P levels at matched
hyperglycemia (P<0.05), suggestive of decreased glucose transport.
In conclusion, postabsorptive hyperglycemia in STZ diabetic rats was
largely due to decreased glucose clearance, although increased HGO
may also have been a contributing factor at the highest STZ dose. The
decrease in postabsorptive glucose clearance in STZ diabetic rats
appeared to be associated with an impairment of glucose transport in
soleus (type I) muscles.
Received 17 June 1997; accepted in final form 27 October 1997.
APS Manuscript Number E288-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 14 November 1997