Comparison of Hepatic Extraction of Insulin and Glucagon in Conscious and Anesthetized Dogs*

Abstract

Previous studies in anesthetized dogs demonstrated that basal hepatic extraction of insulin and glucagon are approximately 50 and 10-20%, respectively. Because of the stress of anesthesia and surgery, these values may not be relevant to normal physiology. In this study, hepatic extraction of insulin and glucagon were compared in conscious and anesthetized dogs. The conscious dogs had chronically implanted catheters in the portal and hepatic vein and the carotid artery and Doppler flow probes on the portal vein and hepatic artery. The mean basal portal vein insulin (42 +/- 10 and 44 +/- 7 microU/ml, respectively) and glucagon (247 +/- 37 and 219 +/- 20 pg/ml, respectively) concentrations were similar in conscious and anesthetized animals. The mean basal portal vein, but not hepatic artery, plasma flow was significantly increased in conscious dogs (462 +/- 62 vs. 294 +/- 35 ml/min, respectively). Despite the increased portal vein plasma flow in conscious animals, the basal hepatic extractions of insulin (42 +/- 6 vs. 39 +/- 6%, respectively) and glucagon (12 +/- 7 vs. 7 +/- 7%, respectively) were similar in both types of animals. Arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion, which increased the amount of insulin and glucagon presented to the liver in conscious and anesthetized dogs, significantly decreased the hepatic extraction of insulin. Hepatic extraction of glucagon did not change in either group of animals. In contrast, infusion of insulin (1.0 mU/kg X min) and glucagon (4 ng/kg X min) into the portal system did not alter hepatic extraction of insulin even though the amounts of insulin and glucagon presented to that organ were similar to those obtained with arginine and CCK-PZ. The basal arterial glucose level was significantly lower in the conscious dogs but the basal hepatic glucose output was similar in the two groups. The glucose response to the infusion of arginine and CCK-PZ and exogenous hormones was significantly greater in the anesthetized animals.

Evidence for direct action of alloxan to induce insulin resistance at the cellular level

“…The reasons for the different results of the studies are not known. There is no evidence that anaesthesia (used in our study) affects insulin extraction [36], or should exert differential effects in diabetic compared with non-diabetic dogs. We observed no relation between clearance and fasting hyperglycaemia that could indicate that changes in clearance were associated with glycaemic control.…”

Cyclic Nucleotide Phosphodiesterase Type 5 Activity Limits Blood Flow to Hypoperfused Myocardium During Exercise

“…LAD coronary blood flow was calculated from the coronary Doppler flow shift with the equation qϭ2.5ϫd 2 ϫf where q is coronary blood flow (in milliliters per minute), d is the internal diameter (ID) of the vessel (in millimeters), and f is Doppler frequency shift (in kilohertz). 9 On the basis of our previous observations, ID was taken to be 80% of external diameter of the artery. Rate-pressure product was calculated as heart rate multiplied by LV systolic pressure.…”

“…Because sildenafil is 84% bound to plasma protein in the dog, 9 this represents a mean plasma-free sildenafil concentration of 66.4Ϯ12.4 nmol/L. …”

Cardiovascular effects of the novel Ca2+‐sensitiser EMD 57033 in pigs at rest and during treadmill exercise

“…Ten minutes later, resting measurements were made with animals both lying and standing followed by the 3-stage exercise protocol as described above. (Ishida et al, 1983). The factor 1.25 is a constant derived from the speed of sound in tissue (C=1.5 10 5 cm s 71 ), the frequency of the emitted sound beam (f 0 =20 MHz), the cosine of the angle at which the sound beam is emitted (458C), and unit conversion factors: (C.0.75 p) / (2f 0 .cos 458C).…”