Yapsin 1 is an aspartic protease from Saccharomyces cerevisiae and belongs to a class of aspartic proteases that demonstrate specificity for basic amino acids. It is capable of processing prohormone substrates at specific basic residue cleavage sites, similar to that of the prohormone convertases, to generate bioactive peptide hormones. An antibody raised against yapsin 1 was previously shown to immunostain endocrine cells of rat pituitary and brain as well as lysates from bovine pituitary secretory granules demonstrating the existence of yapsin 1-like aspartic proteases in mammalian endocrine tissues, potentially involved in peptide hormone production. Here, we show the specific staining of yapsin 1 immunoreactivity in the α-cells of human pancreatic islets. No staining was observed in the β- or δ-cells, indicating a specificity of the staining for glucagon-producing and not insulin- or somatostatin-producing cells. Purified yapsin 1 was also shown to process proglucagon into glucagon in vitro, demonstrating that the prototypical enzyme of this subclass of enzymes can correctly process proglucagon to glucagon. These findings suggest the existence of a yapsin 1-like enzyme exclusively in the α-cells of the islets of Langerhans in humans, which may play a role in the production of glucagon in that tissue.

Abstract

It has previously been shown that the serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin are influenced by genetic effects to various degrees. From a clinical and preventive point of view, however, it is important to identify potentially modifiable non-genetic factors influencing the levels of these measures. Because monozygotic twin pairs share the same genetic background, differences in phenotypic levels within monozygotic twin pairs are believed to be due to non-genetic influences. Accordingly, the associations between intrapair differences in one phenotype and intrapair differences in another phenotype are also due to non-genetic influences. The present sample of 97 pairs of monozygotic twins from the population-based Swedish Adoption/Twin Study of Aging (SATSA) provided the opportunity to assess non-genetic influences on the levels of IGF-I, IGFBP-1, and insulin. Several metabolic measures were found to account for the variation of IGF-I, IGFBP-1, and insulin after controlling for the genetic influences. IGFBP-1 and glucose were significant predictors for the levels of IGF-I. IGFBP-1 and glucose together explained about one quarter of the non-genetic variation of IGF-I. However, when IGFBP-1 was dropped from the regression model, insulin was the only independent predictor of IGF-I, and explained about 19% of the non-genetic variation for IGF-I. For IGFBP-1, insulin and IGF-I were the significant non-genetic predictors. Insulin and IGF-I explained about 28 and 8% respectively of the non-genetic variation for IGFBP-1, while for insulin, IGF-I, triglycerides, body height, glucose, and body mass index (BMI) explained approximately 20, 12, 6, 5 and 5% respectively of the non-genetic variation.

Journal of Endocrinology (1997) 153, 251–257

Familial correlation analyses were used to evaluate the familial aggregation of plasma androgens and androgen glucuronides (testosterone (TESTO), dihydrotestosterone (DHT), androstane-3 alpha,17 beta-diol glucuronide (3 alpha-DIOL-G), and androsterone glucuronide (ADT-G)) in 505 members of 99 white families and 296 members of 111 black families participating in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. Each of these four measures was determined by RIA after separation of conjugated and unconjugated steroid using C18 column chromatography. All participants were sedentary prior to being including in this study. Significant spouse correlations, as well as parent-offspring and sibling correlations, were found for TESTO, DHT, 3 alpha-DIOL-G, and ADT-G in the white sample, suggesting that common familial environments and genes contribute to the familial resemblance. In the black sample, significant sibling and parent-offspring correlations were found for all four phenotypes, while the spouse correlation was marginally significant for 3 alpha-DIOL-G and not significant for TESTO, DHT, and ADT-G. The non-significance of spouse correlations in the black individuals may be due to the small number of spouse pairs. The maximal heritability estimates of TESTO, DHT, 3 alpha-DIOL-G, and ADT-G were 69%, 87%, 74%, and 56% for white individuals and 70%, 73%, 62%, and 48% for black individuals respectively. Sex differences in heritability estimates were found in the white individuals, but they were less dramatic in the black individuals. In conclusion, plasma levels of androgens and androgen glucuronides are highly heritable in both white individuals and black individuals. There are notable sex differences in the white individuals.