Jk. Wi et al., REDUCED GLUCOSE CLEARANCE AS THE MAJOR DETERMINANT OF POSTABSORPTIVE HYPERGLYCEMIA IN DIABETIC RATS, American journal of physiology: endocrinology and metabolism, 37(2), 1998, pp. 257-264
The relationships between postabsorptive glucose concentration and hep
atic glucose output (HGO) and glucose clearance were studied in rats o
ne day after treatment with various doses of streptozotocin (STZ; 0, 1
5, 30, 40, 50, or 75 mg/kg; n = 6 per dose; study 1). Glucose fluxes w
ere estimated using a prolonged (6-h) infusion of [3-H-3]glucose to en
sure complete tracer equilibration at hyperglycemia. Postabsorptive gl
ucose was significantly increased at the high doses of STZ (50 and 75
mg/kg; P < 0.01) and was strongly correlated with glucose clearance ac
ross 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, postabsorptiv
e glucose was increased twofold compared with the control (i.e., zero
dose) group, with no change in HGO and a 45% decrease in glucose clear
ance, indicating that the hyperglycemia was due to a decrease in gluco
se clearance. To understand the cellular mechanisms of decreased gluco
se clearance in STZ diabetic rats, skeletal muscle glucose clearance a
nd intracellular glucose and glucose 6-phosphate (G-6-P) concentration
s 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 matc
hed hyperglycemia (P < 0.05), suggestive of decreased glucose transpor
t. In conclusion, postabsorptive hyperglycemia in STZ diabetic rats wa
s largely due to decreased glucose clearance, although increased HGO m
ay also have been a contributing factor at the highest STZ dose. The d
ecrease in postabsorptive glucose clearance in STZ diabetic rats appea
red to be associated with an impairment of glucose transport in soleus
(type I) muscles.