Arne Nygren

Insulin uptake by the human alcoholic cirrhotic liver

Insulin uptake by the human cirrhotic liver was studied in six patients with Laennecs cirrhosis, and the result was compared with that found in ten control patients with varying diseases affecting the biliary system. All patients had portal catheters for diagnostic purposes. The fractional hepatic uptake of insulin was calculated from the clearance rates for insulin obtained after a constant rate infusion into a peripheral vein and the portal vein in each patient. The fractional hepatic extraction of insulin was 13% +/- 5 in cirrhotic patients and differed significantly from the fractional hepatic extraction found in controls (51% +/- 5;P less than 0.001).

Thyrotropin and prolactin responses to thyrotropin-releasing hormone: Influence of fasting- and insulin-induced changes in glucose metabolism

It has been reported that prolonged fasting inhibits the response of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) in normal persons. To explore possible mechanisms behind this reduced TSH responsiveness and also to see whether dietary factors influence prolactin (PRL) responsiveness, six nonobese volunteers were intravenously injected with a small dose of TRH (25 μg) after three different fasting periods: an 8-hour overnight fast, a 56-hour fast supplemented with oral administration of glucose (4 g/kg/56 h yielding 16 kcal/kg/56 h), and a 56-hour fast supplemented with oral administration of an equicaloric amount of an amino acid (AA) mixture (4 g/kg/56 h) containing 17 different amino acids. The dose of TRH raised the PRL level from 14 ± 2 to 58 ± 8 ng/ml after the overnight fast. Similar PRL responses were obtained after the two prolonged fasting periods. The TRH also raised the TSH level from 1.0 ± 0.0 to 5.2 ± 0.8 μU/ml after the overnight fast. Prolonged fasting with glucose supplementation had no significant effect on this TSH responsiveness, nor did it change the basal blood glucose level. In contrast, prolonged fasting with AA supplementation not only reduced TSH responsiveness by 47 ± 7% (P < 0.002), it also lowered the basal blood glucose level from 4.2 ± 0.1 to 3.5 ± 0.2 mmol/L (P < 0.002). In an additional six normal subjects who fasted overnight, 25 μg TRH was injected intravenously on two occasions: after intravenous infusion of insulin, and after intravenous infusion of saline. The insulin induced market hypoglycemia (1.8 ± 0.1 mmol/L) in 30 ± 3 minutes, whereas saline, infused over a similar time period, had no significant influence on the blood glucose level. When PRL responsiveness was measured during the insulin-induced hypoglycemia, it was found to be increased by 56 ± 15% (P < 0.02). The corresponding TSH responsiveness was decreased by 18 ± 6% (P < 0.05). These results imply that an adequate glucose delivery to pituitary thyrotrophs might be a prerequisite for normal TSH responsiveness. They also show that changes in glucose utilization affect lactotrophs and thyrotrophs differently.

Immunoreactive Insulin in the Portal and the Peripheral Venous Blood after Intravenous Tolbutamide Administration

Immunoreactive insulin has been assayed in portal and peripheral venous blood in fourteen patients with hepatic, pancreatic and gastric disease before and after tolbutamide administration. The difference between portal and peripheral insulin varied considerably in different patients. In some of the patients the portal insulin seemed to increase at a time when peripheral venous insulin had started to decrease. The implication of this finding is discussed.

The influence of indomethacin, theophylline, and propranolol on ethanol augmentation of glucose-induced insulin secretion

The effect of indomethacin, theophylline, and propranolol on ethanol augmentation of insulin secretion after intravenous glucose stimulation was studied. Intravenous glucose tolerance tests were performed with and without pretreatment with oral ethanol. The role of indomethacin was evaluated in six healthy subjects; the effect of theophylline and propranolol on ethanol augmentation in insulin secretion was studied in five and six subjects, respectively. Ethanol pretreatment was followed by increased insulin (P < .01) and C-peptide areas (P < .01) after intravenous glucose (Area, 0 to 20 minutes). Indomethacin suppressed the ability of ethanol to augment insulin (P < .01) and C-peptide (P < .01) responses. Neither theophylline nor propranolol affected ethanol augmentation of insulin secretion. In conclusion, indomethacin probably interferes with the mechanism for ethanol augmentation of glucose-induced insulin secretion. It is suggested that inositol phospholipids take part in the effect of ethanol to augment insulin secretion, and that indomethacin interferes with the metabolism of inositol phospholipids.

Forearm glucose uptake during glucose tolerance tests in chronic alcoholics

In twelve chronic alcoholics the glucose uptake in a forearm segment was studied during glucose tolerance tests. The tests were performed twice in each case, on the 3rd and on the 10th to 14th days after admission to hospital in an intoxicated state after a period of excessive alcohol intake. The total forearm glucose uptake following an oral glucose load almost doubled from the first to the second examination. Arterial glucose and insulin concentrations were similar on the two occasions. The findings indicate that the disposal of an oral glucose load is altered during the recovery after a period of excessive alcohol intake. The contribution made by muscle tissue increases twofold while that of the liver decreases.

The effect of glipizide on extraction of insulin by the human cirrhotic and noncirrhotic liver

The effect of glipizide on hepatic uptake of insulin was studied in five patients with liver cirrhosis and five patients with varying diseases in the biliary system and pancreas. All patients had portal catheters for diagnostic purposes. The hepatic uptake of insulin was estimated from the clearance rate for insulin obtained after a constant rate infusion into a peripheral vein and the portal vein. Each patient was examined on two consecutive mornings, the second investigation carried out one hour after oral glipizide administration. The fractional hepatic uptake was significantly lower in cirrhotic patients (17% +/- 6%) than in the other patients (52% +/- 7%; P less than .01). After glipizide, an increase in the estimated uptake of insulin occurred in cirrhotic patients (from 17% +/- 6% to 39% +/- 6%; P less than .01), whereas an insignificant decrease was observed in the other patients (from 52% +/- 7% to 43% +/- 11%).