Summary
To investigate the hepatic ketone body metabolism in NIDDM, we studied the ketone
body production rates in hepatocytes from newly developed non-obese NIDDM model rats.
NIDDM model rats were prepared by intraperitoneal injection of streptozotocin at 2
or 5 days of age (STZ 2, STZ 5 respectively). After 10-15 weeks, ketone body production
rates in hepatocytes isolated from these rats were compared with those from control
rats as well as ketotic rats made by intravenous injection of streptozotocin into
adult rats. Basal ketone body production rates from 0.3 mM [U-14C] palmitate in hepatocytes from control, STZ 2, STZ 5 and ketotic rats were 11.7±0.98,
14.9±0.72, 16.0±0.45, 22.8±2.32 nmole · palmitate/mg · prot/hr, respectively. These
rates were stimulated by 1 μg/ml of glucagon in control, STZ 2 and STZ 5 rats (14.1±0.99,
18.6±1.36, 18.7±0.69 nmole·palmitate/mg·prot/hr, respectively), but not in ketotic
rats (22.8±2.07 nmole · palmitate/mg · prot/hr). The similar effects were observed
by 1 μg/ml of epinephrine. The basal ketone body production rates were negatively
correlated to both hepatic glycogen contents and plasma IRI levels. Considering these
parameters together, the extent of metabolic derangement in STZ 2 and STZ 5 rats was
between that in control and ketotic rats. These results indicate that the derangements
of hepatic ketone body production are related to the severity of insulin deficiency
and suggest that the enhanced hepatic ketogenesis contributes in part to the elevated
plasma ketone body levels in non-obese NIDDM.
Key words
NIDDM Model Rats - Freshly Isolated Hepatocytes - Ketone Bodies - Glucagon - Insulin
