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Correlation between blood glucose, glucagon and adrenaline levels and gluconeogenesis was studied during the recovery from insulin-induced hypoglycemia in rats. Rats, overnight fasted, were intravenously injected with 40 microCi/kg of [U-14C]-lactate and 1 U/kg of porcine insulin under an anesthesia with pentobarbital sodium. Blood samples were drawn via the peripheral vein at 0, 5, 10 and 20 min. Plasma insulin level was 617 +/- 115 microU/ml at 5 min. Plasma glucose level was significantly decreased at 5 min (2.7 +/- 0.3 mM at 5 min v.s. 4.3 +/- 0.2 mM at 0 min, P < 0.01). Plasma glucagon and adrenaline did not significantly respond at 5 min, and then rised. Specific radioactivity of plasma [1-14C]-glucose was significantly higher at 5 and 10 min in the insulin-injected rat than the saline-injected rat (204 +/- 34 v.s. 130 +/- 14 d.p.m./mumol at 5 min, P < 0.01; 275 +/- 32 v.s. 186 +/- 16 d.p.m./mumol at 10 minm P < 0.01). These results suggest that lowering of blood glucose level stimulates gluconeogenesis independently of the release of counter-regulatory hormones in insulin-induced hypoglycemia.

To estimate the residual beta-cell function, plasma glucose and C-peptide response to an intravenous injection of tolbutamide were observed in seven Type I (insulin dependent) and nine Type II (non-insulin dependent) diabetic patients on insulin therapy. Fasting plasma glucose in the patient was controlled below 11 mmol/l by conventional insulin therapy, and 1 g of tolbutamide was intravenously injected. In the serum C-peptide response following tolbutamide injection, seven of nine Type II diabetics showed the peak values of serum C-peptide more than 0.3 nmol/l from 20 min to 60 min after the load, and Type I diabetics gained the peak values less than 0.3 nmol/l except one patient. The decrease of plasma glucose within 60 min after tolbutamide injection was more than 20% of the basal level in eight of nine Type II diabetics, and in all of seven Type I diabetics the decrease did not exceed 15%. Both serum C-peptide and plasma glucose after tolbutamide load responded differently between Type I and Type II diabetics on insulin therapy, and it was thought that tolbutamide load-glucose response test may be a useful method to estimate the residual beta-cell function in the diabetics.

To evaluate the effect of aging on hepatic extraction of insulin, peripheral plasma insulin and C-peptide levels after an oral glucose ingestion were measured in 39 non-obese healthy subjects with normal glucose tolerance test. The subjects were divided into two groups. One age group was below 30 years (n = 17) and another was above 50 years (n = 22). Blood glucose level was significantly higher in elderly subjects than in young at 30 and 60 min, and insulin level was also significantly higher in elderly subjects than in young subjects at 60 min after glucose ingestion. C-peptide response after glucose ingestion was similar in both groups. The molar ratio of C-peptide to insulin after glucose ingestion in elderly subjects was slightly lower than that in young subjects, and the difference between the incremental areas of C-peptide and insulin divided by the incremental area of C-peptide were significantly lower in elderly subjects. These results suggest that hepatic insulin extraction after glucose loading is decreased in elderly subjects and this may partly be responsible for the slightly altered glucose metabolism in elderly subjects with normal glucose tolerance test.

Glucose output was investigated in bivascularly perfused rat liver. Flow rate was 1 ml/min/g from hepatic artery and 2 ml/min/g from portal vein. Basal glucose output (130 +/- 30 microM/min) from bivascularly perfused liver was significantly (p less than 0.02) higher than that (80 +/- 20 microM/min) from usual monovascularly perfused (3 ml/min/g from portal vein) liver. However, glucagon-induced (1 ng/ml) increment in glucose output from bivascularly perfused liver 589 +/- 127 microM/30 min) was not significantly different from that (630 +/- 127 microM/30 min) of monovascularly perfused liver. These results suggest that glucagon-dependent glucose output was similar in monovascularly and bivascularly perfused rat liver, and that arterial blood supply may have some role in glycogenolysis in the perfused rat liver.

In order to elucidate the effect of hyperglycemia on serum thyroid hormone levels, serum T4 and T3 concentrations were measured in rats with continuous intravenous glucose infusion. 30% glucose solution was infused into the left jugular vein at a rate of 1 ml/hr for 12 hr, and serum glucose level was maintained at 400 mg/dl. Serum T4 levels were slightly but not significantly decreased and serum T3 levels were significantly decreased by infusion of glucose for 12 hr. The ratio of serum T3 to T4 was not significantly changed in rats with glucose infusion. These results suggest an inhibitory effect of hyperglycemia on thyroid hormone release.

To determine the effect of maturation on glucose-induced insulin release after starvation, we investigated the insulin release from perfused pancreas of young adult rats after fasting for 18-20 hr. In the rats weighing 300-400 g (12-14 w) and 200-250 g (7-8 w), the glucose-induced insulin secretion from perfused pancreas of starved rats was similar to that of fed rats. While, in the rats weighing 100-150 g (4-5 w), both the first and the second phase of glucose-induced insulin secretion from perfused pancreas of starved rats was markedly decreased compared with that of fed rats. These results suggest that insulin response to glucose is not matured in young below 150 g (5 w).