Serotoninergic activation and inhibition: effects on carbohydrate tolerance and plasma insulin and glucagon.

Glucose and arginine infusion tests were performed on 12 healthy volunteers (8 males, 4 females) before and after serotoninergic activation [oral administration of L-5-hydroxytryptophan (5-HTP-) for 6 days] and serotoninergic inhibition (oral treatment with D,L-p-chloropenylalanine for 6 days). 5-HTP treatment markedly increased urinary 5-hydroxyindoleacetic acid excretion, increased the mild hyperglycemic effect of arginine infusion, and lowered the glucose disposal rate constant. The adverse effect of serotoninergic activation on glucose tolerance is not sufficiently explained by the observed changes in insulin and glucagon secretion during the fasting state and after intravenous glucose and arginine infusions. Serotoninergic inhibition did not affect the carbohydrate tolerance of normal individuals. The results of this work supports the idea that excessive indoleamine production is probably the main cause for carbohydrate intolerance in carcinoid tumors.

Infusion of synthetic human C-peptide does not affect plasma glucose, serum insulin, or plasma glucagon in healthy subjects.

We studied six healthy male subjects to determine whether a four-hour infusion of synthetic human C-peptide sufficient to achieve mean (+/- SD) peripheral plasma concentrations of 1.3 +/- 0.7 pmol/mL affected plasma glucose, serum insulin, or plasma glucagon. Subjects were studied in a fasting state and following an oral glucose load during four-hour 0.9% NaCl (control) and C-peptide (mean dose: 70 nmol) infusions. No differences were observed between saline and C-peptide infusions for mean values of fasting plasma glucose (94 +/- 6 v 87 +/- 5 mg/dL), serum insulin (3 +/- 1 v 2 +/- 1 microU/mL), or plasma glucagon (124 +/- 65 v 112 +/- 70 pg/dL). Following oral glucose ingestion no differences were detected between saline and C-peptide infusions for mean peak values of plasma glucose (168 +/- 18 v 168 +/- 31) and serum insulin (59 +/- 6 v 57 +/- 21) or mean nadir values of plasma glucagon (80 +/- 73 v 75 +/- 70). There was a slight delay in the insulin rise following oral glucose on the C-peptide infusion day, but differences between mean values for individual sampling times were not statistically significantly different.

Familial ureteral abnormalities syndrome: genomic mapping, clinical findings.

Abnormal development of the ureter during embryogenesis, when occurring in multiple family members, appears to be a genetically determined defect with autosomal dominant inheritance and high penetrance, which can lead to significant kidney damage, renal failure, and death. We have studied 48 individuals within a large kindred in which ureteral-related abnormalities (including vesicoureteral reflux, ureteropelvic junction obstruction, duplicated ureters, and medullary sponge kidney) were segregated. Family members who had not had previous diagnostic studies were evaluated for presence or absence of ureteral abnormalities and we attempted to map the locus for this familial ureteral abnormalities syndrome (FUAS). These studies identified 11 asymptomatic individuals, previously assumed to be unaffected, with minor abnormalities. When linkage analysis between the inheritance of ureteral abnormalities and six marker loci glyoxalase I (GLO- ), major histocompatibility antigens (HLA-A, B, and DR/DQ), D6S288, and factor XIII antigen (F13A1) on the short arm of chromosome 6 was performed, the lod scores significantly rejected linkage over a 77.1-cM distance. These findings are in contrast to previous data suggesting linkage between the presence of ureteral abnormalities and HLA, and indicate the possibility of genetic heterogeneity of FUAS.

Hormonal and metabolic effects of a pancreatic endocrine graft. Vascularized segmental transplantation in insulin-dependent diabetic patients.

A new modification of pancreas transplant technique, the vascularized segmental intraperitoneal graft without duct ligation, has provided reversal of insulin-dependent (type I) diabetes mellitus for as long as 2 years of comfortable life. Although the risks associated with immunosuppression remain high (two of the 12 patients have died of early postoperative infection), selected data are presented from six cases to show the following striking hormonal and metabolic results after transplantation and withdrawal of insulin: restoration of normal beta cell function as shown by 24-hour urine C-peptide excretion and acutely responsive serum insulin, restoration of normal suppressibility of plasma glucagon, elimination of ketosis and negative nitrogen balance, normal fasting plasma glucose and glycosylated hemoglobin, and normal or near-normal glucose tolerance. These results provide a standard for current explorations of new ways of treating insulin-dependent diabetes.

Timing of single daily meal influences relations among human circadian rhythms in urinary cyclic AMP and hemic glucagon, insulin and iron.

Relations among circadian rhythms in serum iron, glucagon and insulin and urinary cyclic AMP excretion differ drastically when diurnally active, nocturnally resting human adults consume all daily food for one week as breakfast only and for another week as dinner only - a finding of interest to diverse fields, e.g., for optimizing certain kinds of therapy or for a better utilization of calories.