Vol. 274, Issue 6, E984-E991, June 1998
Glycemia-lowering effect of cobalt chloride in the diabetic
rat: role of decreased gluconeogenesis
Firas
Saker1,
Juan
Ybarra2,
Patrick
Leahy3,
Richard W.
Hanson3,
Satish C.
Kalhan1, and
Faramarz
Ismail-Beigi2
Departments of 1 Pediatrics,
2 Medicine, and
3 Biochemistry, Case Western
Reserve University, Cleveland, Ohio 44106-4951
Results of previous
studies indicated that treatment of diabetic rats (induced by
streptozotocin) with cobalt chloride
(CoCl2) resulted in a
significant decrement in serum glucose concentration. The present study
was designed to determine the potential role of enhanced glucose uptake
vs. decreased glucose production in the above response. The rate of
systemic appearance of glucose, measured under fasting
conditions using
[3-3H]glucose tracer,
was reduced from 35.5 ± 2.5 to 17.5 ± 1.8 µmol · kg
1 · min1
in diabetic rats treated with 2 mM
CoCl2 added to the drinking water
for 10-14 days (P < 0.01).
Tissue accumulation of intravenously administered
2-deoxy-[14C]glucose
was significantly reduced in kidney and eye of diabetic rats treated
with CoCl2, whereas the uptake
remained unchanged in several other tissues including cerebrum, red and
white skeletal muscle, heart, and liver. The relative content of
phosphoenolpyruvate carboxykinase (PEPCK) mRNA was increased
3.1-fold in livers of diabetic compared with normal rats
(P < 0.001), and treatment of
diabetic rats with CoCl2 decreased
hepatic PEPCK mRNA levels to normal. The content of PEPCK mRNA in the
liver was decreased by 33% in
CoCl2-treated normal rats
(P < 0.05). Treatment with CoCl2 resulted in no change in
cAMP levels in the livers of either diabetic or normal rats. These
results suggest that the glycemia-lowering effect of
CoCl2 is mediated by reductions in
the rate of systemic appearance of glucose and hepatic gluconeogenesis.
glucose uptake; phosphoenolpyruvate carboxykinase mRNA; adenosine 3',5'-cyclic monophosphate
