Aage Prange Hansen

Low cerebrospinal fluid somatostatin in Parkinson disease An irreversible abnormality

In 39 parkinsonian patients, CSF somatostatin content was 88.0 ± 4.1 pg per milliliter, which was about 40% less than in controls (147.3 ± 5.1 pg per milliliter). Somatostatin values were unrelated to age, sex, body weight, total CSF protein, immunoglobulin, or cell count in either group. Parkinsonian values were not related to duration of disease, severity, specific signs, or treatment. In contrast to multiple sclerosis, in which CSF somatostatin is low only during relapses, the low somatostatin content of CSF in Parkinson disease seems to be irreversible, to be present at the onset of symptoms, and to imply an irreparable functional or structural alteration of somatostatin-secreting neurons.

Low somatostatin content in cerebrospinal fluid in multiple sclerosis: AN INDICATOR OF DISEASE ACTIVITY?

In 27 patients with multiple sclerosis (MS), and in 10 control subjects of comparable age, percent ideal body weight and sex ratio, the cerebrospinal fluid (CSF) content of somatostatin was measured by radioimmunoassay.

The Origin of Cerebrospinal Fluid Somatostatin: Hypothalamic or Disperse Central Nervous System Secretion?

The present study deals with the origin of somatostatin in cerebrospinal fluid. Two groups of experiments were performed: (1) Diagnostic lumbar puncture was performed in 37 patients admitted for various neurological diseases. Immunological determination of albumin and gamma-globulin, and radioimmunological analysis of somatostatin in successive cerebrospinal fluid taps demonstrated that while the protein concentration was approximately 20% lower in the 11th ml compared to the 1st ml drawn, the somatostatin concentration was constant. (2) Intravenous arginine infusion (30 G/30 min) induced identical patterns of plasma growth hormone in 8 patients with multiple sclerosis in relapse, in 6 patients with multiple sclerosis in the stable phase, and in 7 patients in whom no neurological disease was eventually diagnosed. Cerebrospinal fluid somatostatin was significantly lower in the patients with multiple sclerosis in relapse than in the two other groups, while cerebrospinal fluid growth hormone concentration was identical. There was no correlation between basal or arginine provoked plasma growth hormone and the cerebrospinal fluid content of somatostatin. The results indicate that cerebrospinal fluid somatostatin is released dispersely from the central nervous system including the spinal cord - and that it offers no indication of the activity or tone of hypothalamic growth hormone release inhibiting control of the pituitary gland.

The Inhibition by Somatostatin of the Thyrotropin Response to Thyrotropin-Releasing Hormone in Normal Subjects

The influence of somatostatin on the TRH-induced TSH secretion was studied in 6 normal subjects. A consistent inhibitory effect of somatostatin was observed. The inhibitory effect occurred with a time lag of more than 5 minutes. In 4 of the subjects a secondary rise in serum TSH was observed after the cessation of somatostatin infusion, suggesting mechanisms other than simple competition at receptor sites.

Twenty-Four-Hour Serum Growth Hormone Levels in Maturity-Onset Diabetics

Serum growth hormone, glucose, and insulin were studied every half hour during a twenty-four-hour period of “daily life” in four groups of subjects: nonobese normal subjects, obese normal subjects, nonobese maturity-onset diabetics, and obese maturity-onset diabetics. It was found that (1) serum growth horomone was uniformly low without meal- and sleep-related peaks in obese normals and diabetics. The twenty-four-hour serum growth hormone level was significantly higher in nonobese subjects than in obese subjects, in both diabetics and normals; (2) the twenty-four-hour serum growth hormone level was more fluctuating and significantly higher in nonobese diabetics than in nonobese normals; (3) there was no difference in the twenty-four-hour serum growth hormone level between obese diabetics and obese normals.

The effect of somatostatin on plasma noradrenaline and plasma adrenaline concentrations during exercise and hypoglycemia

The effect of somatostatin, on the secretion of noradrenaline and adrenaline was studied in eight normal subjects during exercise and in insulin induced hypoglycemia. Plasma growth hormone response to exercise and hypoglycemia was almost totally suppressed by somatostatin. Plasma noradrenaline during exercise tended to be lower during the infusion of somatostatin but the difference was not significant. During the infusion of somatostatin the secretion of adrenaline was increased. This was seen during exercise but was much more pronounced during hypoglycemia. The blood glucose concentration attained after insulin injection was lower during the infusion of somatostatin and evidence is presented which indicates that the higher adrenaline values during hypoglycemia were due to the lower blood glucose values attained. In conclusion the secretion of catecholamines are not inhibited by a dose of somatostatin which nearly totally suppresses the secretion of growth hormone.

A double-blind study of the efficacy of neutral human and porcine insulin in type I diabetes using a glucose-controlled insulin infusion system

The comparative potency of equimolar amounts of soluble porcine and semisynthetic human insulin were studied in ten patients with type 1 diabetes in acute experimental situations. In both situations residual subcutaneous insulin depots were eliminated by intramuscular treatment exclusively with soluble insulin four days before the experiments. Then, practically identical metabolic states were achieved by connecting the patients to a glucose-controlled insulin infusion system (Biostator) 12 hours before the study. In one study, 0.5 g/kg body weight of glucose was administered intravenously as a bolus, and thereafter insulin was infused at a rate of 1.0 mU/kg/min. The decline in blood glucose was rectilinear and identical for the two insulins: y = -1.18x + 206 and y = -1.17x + 205. The insulin effect is well below maximum, and a 10% increase in the infusion rate of insulin was easily detected. Although changes in blood glucose and pancreatic glucagon were identical, a significantly lower plasma growth hormone level was noted after human insulin infusion. In the second study, 24 hours of near-normoglycemia was attained by the glucose-controlled insulin infusion system, the patients being supine and having identical meals at identical intervals. The diurnal blood glucose, plasma growth hormone, and pancreatic glucagon patterns were identical and the total 24 hour insulin consumption was 47.7 +/- 3.5 units and 47.7 +/- 3.7 units for the two insulins.

Circadian Variation of Plasma Growth Hormone in Normal Subjects and Diabetic Patients. Effects of Somatostatin Infusion, Age and Body Weight

When these studies were initiated late in 1968 the 24-h plasma growth hormone pattern in normal subjects was just discovered. Hunter and Rigal (1) had reported raised plasma growth hormone values during night in children. Quabbe and coworkers (2) had found in adults low day time plasma growth hormone values, intermittent bursts during night with high peaks occurring during times of deeper sleep. Glick and Goldsmith (3) had shown an effect of various feeding procedures on the 24-h plasma growth hormone level. Takahashi et al. (4) and Honda et al. (5) had demonstrated that the release of growth hormone during night coincides with the onset of electroencephalographically determined deep sleep. Experiments in which they had delayed or interrupted sleep provided evidence that the nocturnal growth hormone secretion was related to the onset of sleep and did not reflect a true endogenous circadian rhythm in growth hormone secretion. Extensive studies by Parker and coworkers (6, 7) have amply confirmed and extended these findings