Yoshisuke Maruhama

Rapid changes in urinary serine and branched-chain amino acid excretion among diabetic patients during insulin treatment

In a preliminary experiment, we found a good correlation between 24-h urinary amino acid excretion and the 24-h average plasma levels of the same amino acids. Examining diabetics who were just beginning insulin therapy, we found that insulin normalized the abnormally high levels of excretion of branched-chain amino acids and serine. Interestingly, when expressed in terms of mol/g of creatinine, the normalization of serine excretion brought about by insulin was roughly equal to the normalization of glycine excretion brought about by insulin (-0.39 mM/g of creatinine vs. + 0.33 mM/g of creatinine over 24 h). Since plasma serine is primarily produced in the kidneys from glycine, this suggests that insulin affects the regulation of the serine-glycine metabolic pathway. In turn, measurement of urinary serine and glycine may provide a useful gauge of insulin activity in the tissues, including the kidneys.

Further evidence for insulin hypersecretion not as an initial event but as a consequence of body growth and maturation in juvenile-onset obesity

According to our previous study, hyperinsulinism develops not before 10 years of age despite the presence of obesity but during the maturation years of 10-20. We aimed here at examining the growth-related islet B-cell change together with pituitary activity in non-familial juvenile obesity. Measurement of 24 h urine hormones was shown to be useful for evaluation of the diurnal hormones in plasma. In 56 non-obese and obese juveniles, a significantly positive correlation was found between age (6-18 years) and 24 h urine insulin and c-peptide, thus indicating that the age-related absolute value of body weight significantly affects insulin and c-peptide excretions both in non-obese and obese subjects. Consequently, urinary insulin and c-peptide excretions per kg of body weight were highly similar between obese and non-obese juveniles. However, when the lower specific gravity of fat mass compared with lean body mass and the relative shortage of circulating plasma in fat tissues are taken into consideration, it is obvious that obesity by itself specifically augments this physiologic B-cell maturation between 10 and 20 years of age. The possible interactions of growth hormone and pituitary gonadotropin in hyperinsulinism are discussed.

A Pedigree of Homozygous Familial Hyperalphalipoproteinemia

A new form of familial lipoprotein disorder, homozygous hyperalphalipoproteinemia (HALP) was studied in one pedigree through three generations. The proband was a healthy male, 50 years old, who was checked for a distinctive elevation of plasma high-density lipoprotein cholesterol (HDL-C) in a routine screening examination. An intensive family study revealed that the proband and one of his sisters were homozygotic carriers of familial HALP judging by their extremely high concentration of HDL-C (181 mg/dL and 163 mg/dL, respectively). In the homozygotes, the lipid composition of HDL was found to be normal while the ratio of HDL lipids to apoproteins A-I and A-II tended to be increased. All five children of the two homozygous individuals and two additional first degree relatives were considered to be heterozygous, since their HDL-C values were moderately elevated, with other lipid levels being normal. The family study thus substantiated the hypothesis, as Glueck et al insisted in 1975, that this lipoprotein disorder is inherited by autosomal dominant transmission. Longevity analysis revealed that the decreased family members showed life prolongation of 9.8 years on an average compared with the appropriate control population of the same district. Our report might be the first to demonstrate the homozygous form of this longevity syndrome.