Effects of total pancreatectomy on plasma glucagon, insulin and glucose responses to arginine were determined in 5 dogs. Portal vein and femoral artery samples were obtained in response to an arginine infusion (10 g/30 min) prior to, 1 h, 1 day and 1 week after pancreatectomy. Glucagon was measured using pancreatic-specific antiserum 30K (Unger, Dallas). Before pancreatectomy arginine significantly increased portal vein glucagon from 373 plus or minus 36 to 595 plus or minus 31 pg/ml and femoral artery levels from 233 plus or minus 28 to 342 plus or minus 74 pg/ml. Portal vein and femoral artery insulin concentrations of 74 plus or minus 21 and 17 plus or minus 3 muU/ml increased significantly to 173 plus or minus 64 and 31 plus or minus 7 muU/ml. Glucose levels did not change. One h after pancreatectomy, portal vein glucagon decreased to 121 plus or minus 15 pg/ml but increased to 230 plus or minus 42 pg/ml after arginine. Elevated blood glucose and the necessity for insulin treatment established the adequacy of pancreatectomy. Furthermore portal vein insulin levels were undetectable and unresponsive to arginine or a combination of glucose, glucagon, and tolbutamide 1 week after pancreatectomy. One day after pancreatectomy arginine significantly increased portal vein glucagon from 343 plus or minus 42 to 776 plus or minus 152 pg/ml. One week after pancreatectomy basal glucagon values were 374 plus or minus 30 in the portal vein and 360 plus or minus 49 in the femoral artery and responded to 1226 plus or minus 641 and 825 plus or minus 270 pg/ml, respectively, with arginine. Chromatography of plasma from one pancreatectomized dog on Sephadex G-50 after arginine stimulation revealed that much of the material cross-reacting with antibody 30K was eluted from the column earlier than either 125I-insulin or 125I-glucagon. In contrast, peak glucagon activity in plasma obtained from a normal human given arginine eluted from the column between the peak of 125I-insulin and 125I-glucagon; glucagon added to human plasma also was recovered in this same area between the 125I-insulin and 125I-glucagon peaks. These results suggest that some of the material that reacted with 30K antibody and which increased after pancreatectomy in response to arginine has a molecular weight greater than pancreatic glucagon. At autopsy no pancreatic tissue could be identified. Thus, after pancreatectomy, validated by absent insulin responses, the glucagon response to arginine was normal or increased. Since arginine is not thought to increase intestinal glucagon-like immunoreactive material, the source and nature of the material measured as glucagon after pancreatectomy is unknown, but may be important to any understanding of plasma glucagon measurements.

No abstract

Effects of somatostatin (250 ng/kg . min) or saline infusion on hepatic extraction of endogenous and exogenous insulin and glucagon were investigated in anesthetized dogs. After a 20-min control period, somatostatin or saline was infused into the superior mesenteric vein for 100 min. During the final 50 min of the somatostatin or saline infusion, insulin (1.7 mU/kg . min) and glucagon (20 ng/kg . min) were also infused. These infusions were then replaced with a saline infusion for an additional 30 min. Somatostatin rapidly and significantly decreased portal vein insulin and glucagon concentrations. Hepatic extraction of endogenous insulin decreased from the control value of 61 +/- 5% to 29 +/- 10% during the final 20 min of somatostatin infusion before exogenous insulin and glucagon were added to the infusion. The decrease in hepatic extraction of endogenous insulin is based on the mean of the individual values of the eight dogs in the group and may be spurious because of the very low concentrations of insulin which were being measured and the fact that at such low concentrations, some dogs appeared to have negative hepatic extraction of inulin. Glucagon extraction was unchanged (9 +/- 6% compared to 7 +/- 12%) during the first 50 min of infusion of somatostatin. Column chromatography demonstrated that the 3500 mol wt fraction of glucagon comprised 75 +/- 4% of the total glucagon immunoreactivity in the portal vein during the control period and 67 +/- 13% during the infusion of somatostatin. During the final 20 min of somatostatin infusion before the addition of insulin and glucagon, the blood glucose significantly decreased and hepatic glucose output fell from 2.4 +/- 0.4 to 1.4 +/- 0.3 mg/kg . min. However, the insulin to glucagon (3500 mol wt fraction) molar ratio did not change significantly (4.2 +/- 1.1 to 2.6 +/- 0.5). During the final 20 min of the combined infusion of somatostatin, insulin, and glucagon, hepatic extraction of insulin returned to control values and glucagon extraction rose from 7 +/- 12% to 35 +/- 11%. Hepatic glucose output increased without any significant change in the portal vein insulin to glucagon molar ratio. After the termination of the combined infusion, hepatic extraction of insulin was unchanged, but glucagon removal returned to control values. At this time, the portal vein insulin to glucagon ratio rose, and hepatic production of glucose fell below control values. These results demonstrate that somatostatin may influence peripheral insulin and glucagon values by modifying their hepatic extraction and inhibiting their pancreatic secretion. Hepatic glucose output did not always reflect the portal vein insulin to glucagon molar ratio.

Effects of TSH on the adenylate cyclase-cAMP system and some parameters of intermediary metabolism were investigated in human thyroid carcinoma and adjacent normal thyroid tissue. Basal adenylate cyclase activity and cAMP concentrations were significantly higher in carcinomatous tissue. Basal [1-14C]glucose oxidation, 32Pi incorporation into phospholipids, and organification of iodide were similar in both tissues. Stimulation of cAMP by TSH was significantly greater in normal compared to carcinomatous tissue. In neither tissue was there a good correlation between TSH stimulation of adenylate cyclase activity and cAMP concentrations. The TSH stimulation of 32Pi incorporation into phospholipids by TSH was significantly greater in normal tissue. The mean effect of TSH on iodide organification and glucose oxidation was similar in normal and carcinomatous tissue. Although specific binding of TSH was demonstrated in both normal and carcinomatous tissue, it did not correlate very well with stimulation of adenylate cyclase activity. Hormones other than TSH also augmented adenylate cyclase activity in two of the carcinomas. In individual patients, the relative responsivity of carcinomatous tissue compared to normal was not always consistent when all of the metabolic parameters were considered.

The time course of action of regular and NPH insulins injected sc was studied in 15 insulin-treated diabetics over a 24-h period during which they received a constant infusion of glucose. The blood glucose began to decline in 1.2 +/- 0.1 h (range, 0.5--2) and reached its nadir in 5.7 +/- 0.3 h (range, 4--8) after the sc injection of regular insulin. The peak effect of regular insulin usually persisted for several hours, and the total duration of action was 16.2 +/- 1.1 h (range, 9--24). Both the time of peak effect and the total duration of action were considerably prolonged compared to data provided in standard textbooks. Free insulin increased to a peak in 2.7 +/- 0.3 h (range, 1--4) after regular insulin injection and then returned to baseline by 8.8 +/- 0.96 h. Subcutaneous injection of NPH insulin decreased the blood glucose by 2.4 +/- 0.5 h (range, 1--7), with a maximal effect at 11.0 +/- 1.4 h (range, 5--19). The total duration of effect on blood glucose was 25.1 +/- 0.7 h (range, 20--29). These values are similar to those in standard textbooks. Although the total insulin levels increased after the injection of NPH insulin, there was very little if any elevation in free insulin. Recognition of the prolonged effect of regular insulin is important in establishing an insulin treatment regime for diabetic patients.