GLYCEMIA-LOWERING EFFECT OF COBALT CHLORIDE IN THE DIABETIC RAT - ROLE OF DECREASED GLUCONEOGENESIS

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 stud y was designed to determine the potential role of enhanced glucose upt ake vs, decreased glucose production in the above response. The rate o f systemic appearance of glucose, measured under fasting conditions us ing [3-H-3]glucose tracer, was reduced from 35.5 +/- 2.5 to 17.5 +/- 1 .8 mu mol.kg(-1).min(-1) in diabetic rats treated with 2 mM CoCl2 adde d to the drinking water for 10-14 days (P < 0.01). Tissue accumulation of intravenously administered 2-deoxy-[C-14]glucose was significantly reduced in kidney and eye of diabetic rats treated with CoCl2, wherea s the uptake remained unchanged in several other tissues including cer ebrum, red and white skeletal muscle, heart, and liver. The relative c ontent 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 mRN A levels to normal. The content of PEPCK mRNA in the liver was decreas ed by 33% in CoCl2-treated normal rats (P < 0.05). Treatment with CoCl 2 resulted in no change in cAMP levels in the Livers of either diabeti c or normal rats. These results suggest that the glycemia-lowering eff ect of CoCl2 is mediated by reductions in the rate of systemic appeara nce of glucose and hepatic gluconeogenesis.