Abstract

BACKGROUND
Increased availability of plasma free fatty acid (FFA) leads to an inhibition of glucose utilization in peripheral tissue and to an increase of gluconeogenesis in the liver. A previous study has shown that a decrease in plasma FFA profoundly inhitbits hepatic gluconeogenesis, but total hepatic glucose production is maintained due to a com pensatory increase in glycogenolysis. It has been suggested that this hepatic autoregulatory mechanism is defective in the diabetic state, but there has been no firm evidence to confirm this. This study was performed to see the effect of decreasing plasma FFA on plasma glucose and hepatic glucose metabolism in diabetic rats, METHODS: Eight nondiabetic and 8 streptozotocin-induced diabetic rats were used. Blood sampling for plasma glucose and free fatty acid and liver biopsy for measurement of glycogen content were done after intravenous phenobarbital ancsthesia. Acipimox (50 mg/kg in saline) was administered via gastric tube. Plasma glucose and FFA were measured at 30, 60 and 120 min. Liver biopsy was repeated at 120 min. RESULTS: Baseline plasma glucose and FFA were higher in diabetic rats than in nondiabetic rats (18.8 +1.4 mmol/L vs. 6.9+0.8 mmol/L, 720+/-36 umol/L vs. 420+40 umol/L p<0.001 respectively). Hepatic glycogen content was higer in nondiabetic rats (31.8 +1.6mg/g liver vs. 26.02.Dmg/g liver, p<0.01). After acipimox administration, plasma glucose decreased profoundly in diabetic rats (18.8+1.4 mmol/L to 9.2+1.2 mmol/L, p<0.001) but not in nondiabetic rats. Glycogen content was significantly reduced in both groups (p<0.001). However, the difference in the contents was much smaller in the diabetic group compared with the nondiabetic group (6.5+2.1 mg/g liver vs. 19.2+ l.9 mg/g liver, p<0.001). CONCLUSION: 1t is suggested that the intrahepatic autoregulatory mechanism, which maintains hepatic glucose production constant in nondiabetic rats, is defective in diabetic rats.

• Keywords: Free fatty acid;Antilipolystic agent;Hepatic autoregulation;Diabetes;