Insulin and glucagon secretion in hepatic glycogenoses.

Insulin and glucagon secretion was investigated in ten patients with hepatic glycogenosis, types I and III, in order to understand the relationship between hypoglycemia and pancreatic function. In all patients, both oral glucose tolerance and intravenous arginine infusion tests revealed hypoinsulinemia. Decreased urinary C-peptide levels with standard food intake also supported hypofunction of pancreatic beta cells. On the contrary, the normal secretion pattern of glucagon in both types indicated in the arginine loading test, intact alpha cells in the pancreas. Persistent hypoinsulinism, which is apparently an adaptation to hypoglycemia, could be an important cause of nutritional dwarfism in both types of glycogenosis. The usefulness of the measurement of urinary C-peptide, which evaluates the pancreatic function and provides management for normal body growth, is discussed.     

Enhanced Bioavailability of Subcutaneously Injected Insulin Coadministered with Collagen in Rats and Humans

The present study was undertaken to develop an agent that stabilizes insulin injected subcutaneously. ¹²⁵I-Porcine insulin with 0.2 U/kg unlabeled porcine insulin was subcutaneously injected with or without collagen in the rat under the depilated skin of the back. At various times, the radioactivity in subcutaneous tissue was assayed for insulin and its metabolites by gel filtration. The degradation and absorption rate constants of insulin at the subcutaneous injection site were estimated according to a one-compartment model. The degradation rate constant of insulin in the presence of collagen at the injection site was less than half of the control rate. The inhibition was confirmed by increases in the immunoreactive insulin plasma levels and the hypoglycemic effect in rats and healthy volunteers. We postulate that collagen prevents insulin from being degraded by inhibiting proteolytic enzymes, mainly collagenase-like peptidase, in subcutaneous tissue.     

The effects of atrial natriuretic peptide on renal function and the renin-aldosterone system in anesthetized rabbits

To determine the effects of alpha-human atrial natriuretic peptide (ANP) on renal function and the renin-aldosterone system in anesthetized rabbits, ANP (0.05 micrograms/kg/min) or 5% dextrose solution in vehicle control was infused intravenously. The infusion of ANP resulted in a significant decrease in mean arterial pressure with an increase in renal blood flow (RBF). ANP also produced significant increases in urine volume and urinary sodium excretion. ANP tended to increase glomerular filtration rate, filtered sodium load and net tubular reabsorption of sodium. However, there were no significant differences in these parameters compared with control group. Fractional sodium excretion was increased significantly by ANP. Plasma renin activity (PRA) was suppressed only at 30 min after the infusion of ANP, while a significant fall in plasma aldosterone concentration (PAC) lasted even in the recovery period. These results indicate that ANP produces a diuresis and natriuresis through the increased RBF in anesthetized rabbits. It is also suggested that ANP suppresses PAC independent of the inhibition of PRA.     

An emergent aortic and mitral valve replacement for active infective endocarditis preoperatively using extracorporeal ultrafiltration method

We reported a 29-year-old man with active endocarditis complicating aortic and mitral valve regurgitation. The echocardiogram showed a mycotic aneurysm at aortic valvular annulus and a aneurysm of mitral valve. Heart failure was progressive and caused anuria. Prior to emergent double valve replacement, 2,500 ml of water was removed. Then hemodynamics became stationary. Urination was good during and after operation. In this case, complicating acute renal failure, dehydration with extracorporeal ultrafiltration method was very effective for improvement of hemodynamics.     

Prevention of alcohol-induced gastric mucosal injury by prostaglandin E-1

Effects of ethanol and prostaglandin on the glycoprotein synthesis in the gastric mucus cells have been evaluated. The rat gastric mucosal cell were subjected to a short-term tissue culture in the presence of ethanol and prostaglandin E2 (Ornoprostil), using [3H]-proline, [3H]-palmitic acid, [3H]-galactosamine. Low concentration of ethanol (0.05-0.01 M) stimulated the glycoprotein synthesis, but higher concentration of ethanol (0.5-1.5 M) caused a marked reduction in the glycoprotein synthesis. Addition of prostaglandin E2, especially addition of prostaglandin prior to ethanol treatment, has improved the glycoprotein synthesis and secretion in the presence of ethanol. It was suggested that addition of prostaglandin resulted in the stabilization of the synthesis and secretion of the mucus glycoprotein in the presence of ethanol.     

123I-IMP accumulation in the lung with bronchial asthma--early uptake and delayed washout

123I-IMP is taken up by the pulmonary capillary endothelial cells during the first pass through the lung, and is slowly released from them. To look up the factors which influence on the prolonged 123I-IMP retention in the diseased lung, we examined the correlation between the 123I-IMP uptake during the first pass and the 123I-IMP retention. Patients with bronchial asthma had no abnormal finding in the chest X-ray photograph. However 123I-IMP release from their lungs was delayed. Some patients show a tendency that 123I-IMP uptake during the first pass was uneven, which suggested the change in amine uptake function of endothelial cells. However their correlation coefficients between the uptake during the first pass and the prolonged retention were very small. It was considered that the prolonged 123I-IMP retention in the diseased lung was not explained only by the change in uptake function of pulmonary capillary endothelial cell.     

Role of bradykinin in the regulation of blood pressure and renal blood flow in DOCA-salt hypertensive rats

We examined the role of bradykinin in the onset and/or the maintenance of blood pressure and renal blood flow in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by using a competitive antagonist of bradykinin [Arg-Pro-Hyp-Gly-Thi-Ser-Dphe-Thi-Arg; Hyp, L-4-hydroxyproline; Thi, beta-(2-theinyl-L-alanine)]. The intravenous injection of the bradykinin antagonist (25, 50 and 100 micrograms) produced an increase in mean arterial pressure in all rats treated with tap water, 1% NaCl and DOCA + 1% NaCl. However, the magnitude of the increase in mean arterial pressure was significantly lower in the DOCA-hypertensive rats than in the two groups of rats drinking tap water and 1% NaCl after 4 and 6 weeks, but there was no significant difference after 2 weeks. The bradykinin antagonist induced a decrease in renal blood flow in all rats. However, the extent of the fall in renal blood flow was reduced in the DOCA-hypertensive rats compared with the control rats drinking tap water. These results suggest that endogenous bradykinin is depressed in the established phase of hypertension in DOCA-hypertensive rats. It is also suggested that endogenous bradykinin may counteract the elevation of vascular resistance in the early stages of this model.