Search

Glomerular filtration rate (GFR) was measured by constant infusion of iothalamate in conscious rats with and without streptozotocin diabetes. Kidney weight had already increased significantly after 4 days of diabetes. GFR was unchanged at that time, but increased subsequently, so that GFR/kidney weight was normal after 1 month of diabetes. Tubular glucose reabsorption rate was increased to the same extent as kidney weight after 4 days of diabetes. It is concluded that renal growth in experimental diabetes cannot be initiated by glomerular hyperfiltration, but that increased glucose reabsorption may have a causal role.

In a double-blind randomised trial patients with acute herpes zoster received either 5 mg/kg acyclovir (27) or placebo (29) intravenously three times daily. Acyclovir significantly improved the rate of healing of the skin lesions and shortened the period of pain in the acute phase of zoster. Particularly responsive patients were those above 67 years, those with fever, and those with less than four days of pain before treatment. No adverse effects were observed. Acyclovir seems to be active against varicella/zoster virus.

The role of incubation damage in the radioimmunoassay of human plasma insulin, human plasma growth hormone and rat plasma growth hormone was studied. Damage was measured as the fraction of labelled material which migrated from the origin in wick paper chromatography of samples without antibody. The experiments demonstrated, that recovery of added hormone differed increasingly from 100% as incubation damage increased. Recoveries were found to be too high using the double antibody technique, and too low using chromatographic technique. However, satisfactory recoveries could be obtained in chromatographic assay after correction for the experimentally determined incubation damage using the general formula: % Bound=100 × (B-KD)/(100-KD) where B is the apparent antibody-bound fraction, D the damage fraction, both expressed as percent of the total radioactivity. K is determined experimentally.

The kidney growth seen after the induction of experimental diabetes in rats has been compared to the compensatory renal growth after one-sided nephrectomy. After five days the kidney weight had increased from 650 +/- 15 mg in a group of controls to 778 +/- 21 mg in diabetic rats, and 764 +/- 17 mg in unilaterally nephrectomised rats. The increased weight was in both groups reflected in an increased DNA content and increased RNA/DNA and protein/DNA ratios. In a group of rats made diabetic and nephrectomised at the same time, kidney weight increased to 953 +/- 22 mg after five days. When rats were unilaterally nephrectomised after 20 days of untreated diabetes, compensatory growth was much more pronounced than in non-diabetic rats, kidney weight rising from 780 +/- 21 to 1144 +/- 39 mg in five days. Similarly, in rats with established compensatory renal hypertrophy, diabetes induced a very rapid growth of the remaining kidney (1226 +/- 46 mg after five days).

Somatostatin (SRIF) was given to normal subjects in the fasting state as well as during glucose infusions. During basal conditions a decrease was observed in blood glucose, plasma insulin, and plasma pancreatic glucagon. Plasma free fatty acids (FFA) showed a late 50 per cent increase, beginning approximately 15 min after start of the infusion, whereas basal plasma growth hormone was unchanged. When glucose was infused in other experiments, to suppress plasma pancreatic glucagon before somatostatin administration, no fall in blood glucose was seen in five out of six experiments, and plasma FFA showed no variations. The results suggest that plasma pancreatic glucagon is of major importance for the maintenance of basal blood glucose.

Streptozotocin diabetic rats have larger kidneys than non-diabetic rats. In the present study the rate of kidney growth during the first seven days of diabetes was correlated with the blood glucose concentration. Over a wide range of blood glucose concentrations (116-340 mg/100 ml) the kidney weight, protein content and protein/DNA ratio were closely correlated with the glucose values.

One hundred and ten consecutive diabetic patients with acute myocardial infarction (AMI) were compared to a matched group of non-diabetics with AMI, and the pain experienced during the acute episode by each patient was estimated by counting the number of morphine injections given. No significant difference was found regarding the frequency of painless infarctions, the distribution of injections given during the first three days in the coronary unit, or the need for injections after that time. We conclude that contrary to the common supposition, painless AMI in hospitalised patients is almost as frequent among nondiabetics as among diabetics.

Renal hypertrophy in rats with streptozotocin diabetes or after unilateal nephrectomy was studied by sterological techniques. -- After 4 days of diabetes total glomerular volume had increased by 30%, and after 47 days by 43%. Glomerular growth was more pronounced than whole kidney growth during the first 4 days, but subsequently whole kidney growth exceeded glomerular growth. In control rats glomerular volume was 4.9% of total kidney volume; after 4 days of diabetes it was 5.4% and after 47 days 4.1%. -- Proximal tubule length increased from 366 m/kidney in control rats to 447 m/kidney after 47 days of diabetes; tubular luminal diameter increased from 26.8 micrometer to 31.4 micrometer in the same rats. Tubular length and luminal diameter were, however, not increased after 4 days of diabetes. -- In unilaterally nephrectomised rats there was no early rapid glomerular growth. Glomerular fractional volume was 4.9% in controls, 4.4% at four days, and 4.2% at 24 days after nephrectomy. -- The results indicate a disturbed glomerulo-tubular balance in the early phases of diabetic renal hypertrophy.

Juvenile diabetic patients were studied 60-72 hours after insulin withdrawal when moderate ketoacidosis had developed. Somatostatin infusion for 4 hours in five patients resulted in almost complete suppression of plasma pancreatic glucagon and growth hormone, a fall in plasma-cyclic-adenosine-monophosphate (A.M.P.) concentrations, and a large fall in plasma-glucose concentration. After infusion plasma concentrations of these substances rose again. Blood-ketone-bodies, plasma-free-fatty-acids (F.F.A.), and plasma glycerol concentrations, however, did not decrease appreciably with somatostatin administration. In three patients 2 to 3 h somatostatin infusions were twice superimposed upon a continuous 9-5 h insulin infusion (1 unit/h). An insulin effect was noticeable within 30 minutes, with pronounced falls in the concentrations of plasma glucose, pancreatic glucagon, F.F.A., and blood-ketone-bodies. There was no significant change in these patterns when somatostatin was administered or withdrawn. These results do not indicate that somatostatin infusion would be useful in the treatment of manifest diabetic ketoacidosis.

Based on the literature and on experience and on experience with 23 cases the clinical diagnosis of insulinomas is reviewed. In clinical praxis the diagnostic steps can usually be simplified to a demonstration of fasting, symptomatic hypoglycaemia. Hence, we have used the 72-hour fast as the single diagnostic test for insulinomas during the last 5 years. Pro-insulin measurements may be a valuable supplementary tool. Other diagnostic tests are probably of little importance.

The biomechanical properties of skin and aorta were studied in rats with experimental (streptozotocin) diabetes. After 30 days of diabetes the collagen content of the skin was diminished by 30%. By biomechanical testing collagen from diabetic rats was found to exhibit increased stiffness and strength: maximal stiffness was increased by 20% and the strain at maximum stress was decreased by 10%. Insulin treatment prevented all changes. No differences were found between aortic specimens from diabetic and normal rats.

Different renal structures were studied during the initial phases of compensatory renal hypertrophy. Four days after unilateral nephrectomy, kidney weight had increased by 31%, total glomerular volume by 17%, and glomerular filtration surface by 10%. After 24 days, kidney weight had increased by 44%, glomerular volume by 24%, and filtration area by 22%. The proximal tubules increased their cell volume and diameter significantly after four days (30% and 11%), but tubular length did not increase until later. We conclude that during compensatory renal hypertrophy glomerular growth is less pronounced than tubular growth, and that the increase in filtration surface area is not sufficient to explain the increased glomerular filtration rate after nephrectomy. Proximal tubules initially grow transversally and only later on longitudinally, the two growth phases possibly corresponding to cellular hypertrophy and hyperplasia.

Thermal stability (measured as isometric contraction force), biomechanical properties and reducible cross-links were measured in tail tendons from streptozotocin diabetic rats, with and without insulin treatment. After 10 days of diabetes the maximum thermal contraction force was unchanged, but the relaxation following the maximal contraction was retarded. After 30 days the maximum contraction force was increased and the relaxation rate was decreased. The maximum strength and stiffness of the tendons were increased after 10 days of diabetes and even more after 30 days. There was no change in the density of reducible cross-links. However, diabetes increased the amount of glucose attached to the lysine and hydroxylysine residues of collagen. Insulin treatment prevented all changes in thermal stability and mechanical properties. The results indicate that stabilization of collagen fibres in diabetes does not follow the same pattern as that seen in normal ageing.

Injection of somatostatin, the hypothalamic growth-hormone-inhibiting factor, lowered basal plasma-insulin levels. In intravenous glucose-tolerance tests in five normal subjects, glucose-induced insulin release was markedly suppressed and the glucose-disappearance rate was lowered after somatostatin. Perfusion experiments on the isolated canine pancreas showed that somatostatin acts directly on the beta cells, causing suppression of the initial and the late sustained insulin release phase.

Preliminary studies indicate that somatostatin (SRIF, somatropin release inhibiting factor) can suppress exercise-induced plasma growth hormone rise in normal subjects as well as in diabetics.