Genetic ablation of the preptin-coding portion of Igf2 impairs pancreatic function in female mice.

Preptin is a 34-amino acid peptide derived from the E-peptide of pro-insulin-like growth factor 2 and is co-secreted with insulin from ß-cells. Little is understood about the effects of endogenous preptin on whole body glucose metabolism. We developed a novel mouse model in which the preptin portion of Igf2 was genetically ablated in all tissues, hereafter referred to as preptin knockout (KO), and tested the hypothesis that the removal of preptin will lead to a decreased insulin response to a metabolic challenge. Preptin KO and wild-type (WT) mice underwent weekly fasting blood glucose measurements, intraperitoneal insulin tolerance tests (ITT) at 9, 29, and 44 wk of age, and an oral glucose tolerance test (GTT) at 45 wk of age. Preptin KO mice of both sexes had similar Igf2 exon 2-3 mRNA expression in the liver and kidney compared with WT mice, but Igf2 exon 3-4 (preptin) expression was not detectable. Western blot analysis of neonatal serum indicated that processing of pro-IGF2 translated from the KO allele may be altered. Preptin KO mice had similar body weight, body composition, ß-cell area, and fasted glucose concentrations compared with WT mice in both sexes up to 47 wk of age. Female KO mice had a diminished ability to mount an insulin response following glucose stimulation in vivo. This effect was absent in male KO mice. Although preptin is not essential for glucose homeostasis, when combined with previous in vitro and ex vivo findings, these data show that preptin positively impacts ß-cell function.NEW & NOTEWORTHY This is the first study to describe a model in which the preptin-coding portion of the Igf2 gene has been genetically ablated in mice. The mice do not show reduced size at birth associated with Igf2 knockout suggesting that IGF2 functionality is maintained, yet we demonstrate a change in the processing of mature Igf2. Female knockout mice have diminished glucose-stimulated insulin secretion, whereas the insulin response in males is not different to wild type.

Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo.

Several hormones that regulate nutritional status also impact on bone metabolism. Preptin is a recently isolated 34-amino acid peptide hormone that is cosecreted with insulin and amylin from the pancreatic beta-cells. Preptin corresponds to Asp(69)-Leu(102) of pro-IGF-II. Increased circulating levels of a pro-IGF-II peptide complexed with IGF-binding protein-2 have been implicated in the high bone mass phenotype observed in patients with chronic hepatitis C infection. We have assessed preptin's activities on bone. Preptin dose-dependently stimulated the proliferation (cell number and DNA synthesis) of primary fetal rat osteoblasts and osteoblast-like cell lines at periphysiological concentrations (>10(-11) M). In addition, thymidine incorporation was stimulated in murine neonatal calvarial organ culture, likely reflecting the proliferation of cells from the osteoblast lineage. Preptin did not affect bone resorption in this model. Preptin induced phosphorylation of p42/p44 MAP kinases in osteoblastic cells in a dose-dependent manner (10(-8)-10(-10) M), and its proliferative effects on primary osteoblasts were blocked by MAP kinase kinase inhibitors. Preptin also reduced osteoblast apoptosis induced by serum deprivation, reducing the number of apoptotic cells by >20%. In vivo administration of preptin increased bone area and mineralizing surface in adult mice. These data demonstrate that preptin, which is cosecreted from the pancreatic beta-cell with amylin and insulin, is anabolic to bone and may contribute to the preservation of bone mass observed in hyperinsulinemic states such as obesity.

Preptin derived from proinsulin-like growth factor II (proIGF-II) is secreted from pancreatic islet beta-cells and enhances insulin secretion.

Pancreatic islet beta-cells secrete the hormones insulin, amylin and pancreastatin. To search for further beta-cell hormones, we purified peptides from secretory granules isolated from cultured murine beta TC6-F7 beta-cells. We identified a 34-amino-acid peptide (3948 Da), corresponding to Asp(69)-Leu(102) of the proinsulin-like growth factor II E-peptide, which we have termed 'preptin'. Preptin, is present in islet beta-cells and undergoes glucose-mediated co-secretion with insulin. Synthetic preptin increases insulin secretion from glucose-stimulated beta TC6-F7 cells in a concentration-dependent and saturable manner. Preptin infusion into the isolated, perfused rat pancreas increases the second phase of glucose-mediated insulin secretion by 30%, while anti-preptin immunoglobulin infusion decreases the first and second phases of insulin secretion by 29 and 26% respectively. These findings suggest that preptin is a physiological amplifier of glucose-mediated insulin secretion.

Development during adolescence. The impact of stage-environment fit on young adolescents' experiences in schools and in families.

Although most individuals pass through adolescence without excessively high levels of "storm and stress," many do experience difficulty. Why? Is there something unique about this developmental period that puts adolescents at risk for difficulty? This article focuses on this question and advances the hypothesis that some of the negative psychological changes associated with adolescent development result from a mismatch between the needs of developing adolescents and the opportunities afforded them by their social environments. It provides examples of how this mismatch develops in the school and in the home and how it is linked to negative age-related changes in early adolescents' motivation and self-perceptions. Ways in which more developmentally appropriate social environments can be created are discussed.

Are adolescents the victims of raging hormones: evidence for activational effects of hormones on moods and behavior at adolescence.

The literatures on hormone changes at adolescence, hormonal influences on moods and behavior in nonhuman animals and adult humans, and mood and behavioral changes at adolescence and the small but burgeoning literature on hormonal influences at adolescence are examined. The focus is on moods and behaviors often identified as typically adolescent (e.g., mood lability, mood intensity, irritability, conflict with parents) and the primary hormones of puberty (i.e., the adrenal androgens, gonadotropins, and sex steroids). Through an integration of these literatures evidence is assessed for specific hormone-mood and hormone-behavior associations, as well as for more general types of hormone-outcome relations that transcend specific hormones or outcomes. Non-biological factors that appear to be important in moderating the role of hormones in adolescent moods and behavior are identified. Implications for the design of future studies in this area are detailed.

Caught between parents: adolescents' experience in divorced homes.

This study examined adolescents' feelings of being caught between parents to see whether this construct helps to explain (1) variability in their postdivorce adjustment and (2) associations between family/child characteristics and adolescent adjustment. Adolescents 10 to 18 years old (N = 522) were interviewed by telephone 4 1/2 years after their parents' separation. Feeling caught between parents was related to high parental conflict and hostility and low parental cooperation. Being close to both parents was associated with low feelings of being caught. The relation between time spent with each parent and feeling caught depended on the coparenting relationship. Adolescents in dual residence were especially likely to feel caught when parents were in high conflict, and especially unlikely to feel caught when parents cooperated. Feeling caught was related to poor adjustment outcomes. Parental conflict was only related to adjustment outcomes indirectly, through adolescents' feelings of being caught.

Parents' and teachers' beliefs about adolescents: Effects of sex and experience.

Three studies examine beliefs that parents and teachers have about adolescents. A distinction is made between category-based beliefs (concerning adolescents as a group) and target-based beliefs (concerning individual adoles cents). In Study 1, 90 late elementary and junior high school teachers indicated degree of agreement with a set of category-based statements about adolescents. Parents of early adolescents in Study 2 (N=1272) responded to category- and target-based statements. Study 3 compares the responses of teachers in Study 1 and parents in Study 2. Both teachers and parents endorsed beliefs that adolescence is difficult, and that adults can have an impact. Compared to fathers, mothers believed more in difficulty and in the negative effects of biological change on behavior. Parents of daughters believed adolescence is more difficult than parents of sons. Among teachers, amount of experience with adolescents was positively associated with the belief that adolescence is a difficult period of life. For parents, the effect of amount of experience was mixed. Experience had a greater impact on the category-based beliefs of teachers than parents. Possible influences on the origins and modification of beliefs are discussed.