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Biomedical subjects

D Le Roith

Publications and source records attributed to D Le Roith.

13 recordsLinked to original sources
PubMed1987

Insulin receptors and insulin action in dissociated brain cells.

The present study was conducted to characterize insulin receptors and insulin action in rat brain cells. Binding of [125I]insulin to cells obtained by mechanically dissociating rat brains was 86% specific, time-dependent and reached equilibrium within 90 min. The t1/2 of association was 14 min and t1/2 of dissociation was 8 min. Scatchard analysis demonstrated the typical curvilinear plot providing high affinity (0.03 nM) and low affinity (6.6 nM) binding sites. The total number of binding sites were 0.15 pmol/mg protein. Crosslinking of [125I]insulin to its receptors on dissociated brain cells followed by SDS-PAGE and autoradiography showed that the alpha-subunit of the receptor had a molecular weight of 122,000. This was in contrast with a molecular weight of 134,000 for the liver alpha-subunit. Incubation of dissociated brain cells with insulin resulted in a concentration-dependent inhibition of total [3H]norepinephrine (NE) uptake. This inhibitory effect of insulin on [3H]NE uptake was sodium ion-dependent suggesting that 80-90% of the sodium ion-dependent uptake was insulin-sensitive. Incubation of lectin-purified insulin receptors with insulin resulted in a time- and concentration-dependent stimulation of phosphorylation of the tyrosine residue of an exogenous substrate poly (Glu, Tyr) (4:1). In addition, insulin also stimulated the autophosphorylation of the beta-subunit of the insulin receptors. These observations corroborate our contention that insulin exerts neuromodulatory effects mediated by the specific insulin receptors in the brain.

Animals↗
PubMed1979

Amyloid goitre in familial Mediterranean fever.

Three patients known to suffer from familial Mediterranean fever (FMF), systemic amyloidosis and chronic renal failure developed large amyloid goitres. Amyloid goitre is an extremely rare complication of systemic amyloidosis not previously described in FMF. The clinical and pathological features of these three cases were similar to those previously described in amyloid goitre. In two of the patients abnormalities in thyroid function were consistent with those documented in chronic renal failure. There was evidence of hypothyroidism in a third patient. There was no evidence of amyloid induced dysfunction of other endocrine organs.

Adult↗
PubMed1979

Bromocriptine in hyperprolactinemic amenorrhea: a possible early effect on ovarian steroidogenesis.

The effect of bromocriptine was studied in a 28-year-old cretin woman who presented with long-term untreated primary hypothyroidism, primary amenorrhea, hyperprolactinemia, and an enlarged pituitary fossa. Bromocriptine therapy lowered the plasma prolactin and caused an early rise in plasma 17 beta-estradiol levels and uterine bleeding, despite the failure of plasma gonadotrophins to respond to luteinizing hormone release hormone (LHRH) administration. Thus, it is suggested that bromocriptine may have an early direct effect on the ovary in hyperprolactinemic amenorrhea.

Adult↗
PubMed1979

Medullary carcinoma of the thyroid.

Three patients with medullary carcinoma of the thyroid gland, one sporadic and two familial, are described. One of the patients presented at a late stage of the disease with evidence of wide dissemination and severe diarrhea, which was controlled by indomethacin. The value of venous catheterization and plasma thyrocalcitonin measurements in evaluating the extent of the disease was demonstrated in this case.

Adult↗
PubMed1978

Renal function during treatment of inappropriate secretion of antidiuretic hormone with demeclocycline.

Two patients with the syndrome of inappropriate secretion of antidiuretic hormone were studied in a metabolic ward during treatment with 1.2 g demeclocycline daily. In both patients, demeclocycline treatment led to increased renal water excretion with consequent correction of hyponatremia and hypo-osmolality. Three episodes of reversible deterioration in glomerular filtration rate developed in these patients. Each episode was accompanied by clinical evidence of extracellular fluid volume contraction, and on each occasion there was an inappropriate natriuresis with daily urinary sodium excretion remaining above 50 mEq. Although demeclocycline effectively reverses the electrolyte abnormalities of this syndrome, the potentially dangerous side effects that may develop exclude the routine usage of the drug.

Demeclocycline↗
PubMed1976

The effect of different preparations of human growth hormone on plasma renin activity in normal males.

The effect of acute administration of 2 preparations of growth hormone (hGH) on plasma renin activity (PRA) was studied in normal volunteers. 4 IU of standard, commercially available hGH II, Kabi, Sweden) were injected im into each of four normal subjects, and the PRA was determined in the basal state and at 30, 60, 120, 180, and 240 min after injection. Free fatty acid (FFA) was determined basally and at 15 and 210 min post-injection. The study was repeated on a different day in the same group using highly purified hGH (hGH I, 4 IU) virtually free of arginine-vasopressin. Four other normal subjects received 12 IU standard hGH (hGH II, Kabi, Sweden). There was no significant difference in PRA values with 4 IU of either preparation or with 12 IU of hGH II in any of the groups, although mean PRA was elevated in two of the patients receiving 12 IU hGH II. A rise in FFA occurred in all subjects, indicating the biological activity of hGH preparations. The possible significance of these findings to the renin-angiotensin system found in acromegaly is considered.

Acromegaly↗
PubMed1975

Somatostatin and serum gastrin in normal subjects and in patients with pernicious anaemia, chronic liver and renal disease.

The effects of somatostatin (growth hormone release inhibiting hormone) on basal gastrin were studied in patients suffering from pernicious anaemia and chronic renal and liver disease, and during sequential arginine/insulin-stimulated gastrin release in normal subjects. When basal gastrin concentrations were normal (10-50 pg/ml) in controls and in patients who were in renal and liver failure, somatostatin had no effect on gastrin levels. Raised basal gastrin levels in pernicious anaemia and in 2 cases of chronic renal disease, were significantly inhibited by somatostatin with a half-life (T 1/2) of 3-4 minutes. Arginine infusion caused an insignificant rise in serum gastrin which was unaffected by somatostatin, whereas insulin hypoglycaemia significantly stimulated gastrin release, which was inhibited by somatostatin.

Adult↗
PubMed1975

Disappearance rates of plasma growth hormone after intravenous somatostatin in renal and liver disease.

Plasma immunoreactive growth hormone (hGH) was measured before, during and after the administration of intravenous somatostatin to 3 patients with chronic renal failure and 4 with severe liver disease who had elevation of basal hGH. During somatostatin infusion, the hGH levels declined acutely in a linear fashion when log hGH was plotted against time. Rather surprisingly, the plasma hGH half disappearance time (t 1/2) was 27 min and 18 min in liver and renal disease respectively. These values do not differ from data obtained on normal subjects using exogenous hGH, labelled or unlabelled. Control data on normal subjects using this technique are not available as it was not possible to measure subnormal levels of plasma hGH with the required precision. It is possible that our findings of plasma hGH T 1/2 in liver and renal disease within the normal range reported using exogenous hGH might suggest that high levels of plasma hGH found in these two diseases are primarily caused by hypersecretion rather than impaired clearance.

Growth Hormone↗
PubMedDate not supplied

Hypothalamic-pituitary function in Cushing's disease.

Hypothalamic pituitary function was evaluated in seven patients with Cushing's disease. In all subjects there was an absence of GH elevation following hypoglycemia. Three patients demonstrated basal hyperprolactinemia. Six had an intact PRL rise following TRH. However, four patients failed to show PRL elevation with insulin hypoglycemia and six were unresponsive to chlorpromazine. Five patients showed impaired TSH response to TRH. Many of the subjects had low basal LH and FSH levels. Attenuated or absent gonadotropin responses to LHRH were noted in three females. One male demonstrated an exaggerated FSH response to LHRH. These results indicate that multiple abnormalities of anterior pituitary hormone secretion characterize Cushing's disease.

Adult↗