Sex-steroid milieu determines diabetes rescue in pttg-null mice

Fraenkel, Merav; Caloyeras, J; Ren, Shengxiang; Melmed, Shlomo

doi:10.1677/joe.1.06656

Cited by 18 publications

(17 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…39,40 In turn, these effects could lead to specific differences in synthesis and release of adipokines. As powerful stimulatory effects of estrogen replacement on circulating adiponectin levels have been observed in male gonadectomized pgtt-null mice, 41 a permissive role of gonadal hormones in the differential adipokine profile observed in selected male and female mice in the present study can be anticipated.…”

Section: Discussionmentioning

confidence: 61%

Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity

et al. 2008

View full text Add to dashboard Cite

Objective: Increased dietary fat intake is a precipitating factor for the development of obesity and associated metabolic disturbances. Physically active individuals generally have a reduced risk of developing these unhealthy states, but the underlying mechanisms are poorly understood. In the present study, we investigated the effects of feeding a high-fat diet (HFD) on obesity development and fuel homeostasis in male and female mice with a trait for increased physical activity and in their controls. Methods: Male and female mice selectively bred for a high level of wheel running behavior over 30 generations and nonselected controls (background strain Hsd:ICR) were maintained on a standard lab chow high-carbohydrate diet (HCD) or on an HFD (60% fat). Food intake, body weight, indirect calorimetry parameters, spontaneous locomotor activity and several hormones relevant to metabolism and energy balance were measured. Results: On HFD, mice reduced food intake and increased body fat mass and plasma leptin levels, with the notable exception of the selected females, which increased their ingested calories without any effects on body mass or plasma leptin levels. In addition, they had an elevated daily energy expenditure (DEE), increased spontaneous cage activity (B700% relative to controls) and higher resting metabolic rate (RMR) on the HFD compared with feeding the HCD. The selected males also had a higher DEE compared with controls, but no interaction with diet was observed. On HCD, adiponectin levels were higher in selected male, but not female, mice relative to controls. A marked increase in the level of plasma adiponectin was observed on the HFD in selected females, an effect of diet that was not observed in selected males. Conclusion: Genetically based high locomotor activity renders female, but not male, mice resistant to HFD-induced obesity by alterations in behavioral, endocrine and metabolic traits that facilitate fat utilization rather than limiting HFD intake. International Journal of Obesity (2008) IntroductionObesity is becoming an increasingly prevalent health problem among individuals in affluent societies, because it is often associated with metabolic derangements such as impaired glucose tolerance, insulin resistance, high blood pressure, dyslipidemia and abdominal obesity. When these metabolic abnormalities are displayed in concert (often referred to as the 'metabolic syndrome'), they have a high risk of developing into life-threatening conditions such as cardiovascular disease and diabetes mellitus type 2 (for review, see Moller and Kaufman 1 ). Consensus exists that increased dietary fat intake in combination with a sedentary lifestyle are precipitating factors (World Health Organization), 2 but the underlying endocrine and metabolic mechanisms are poorly understood.A major part of the current knowledge on the etiology of obesity and the metabolic syndrome has come from studies on rodents subjected to a high-fat diet (HFD). [3][4][5][6][7] In particular, the use of selectively bred and geneticall...

show abstract

Section: Discussionmentioning

confidence: 61%

Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Several models of PTTG deficiency have been developed to study the role of PTTG in tumorigenesis and in other pathophysiologic processes, including diabetes (Wang et al 2001, Abbud et al 2005, Chesnokova et al 2005, Donangelo et al 2006, Fraenkel et al 2006, Kim et al 2007a. Although PTTG knockout (PTTGK/K) mice initially appeared viable and fertile (Wang et al 2001), female subfertility, testicular and splenic hypoplasia, thymic hyperplasia, and thrombocytopenia have been noted in these mice (Wang et al 2001).…”

Section: Transgenic Modelsmentioning

confidence: 99%

“…TRb PV/PV PTTGK/K mice had smaller thyroid glands compared with the PTTGC/C mice and exhibited decreased thyrocyte proliferation as well as FTC aggressiveness reflected in slower tumor progression and increased survival (Kim et al 2007a). In PTTGK/K male mice, PTTG deficiency affects pancreatic b-cell proliferation and induces diabetes (Wang et al 2003, Fraenkel et al 2006, often associated with weight loss, increased food uptake, and polyuria as well as decreased islet mass and b-cell proliferation (Wang et al 2003). Thus, animal models have provided solid evidence of tumor-inducing capacity of PTTG, particularly in endocrine organs.…”

Section: Transgenic Modelsmentioning

confidence: 99%

Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update

Salehi

Kovács²,

Scheithauer³

et al. 2008

Endocrine Related Cancer

119

View full text Add to dashboard Cite

Pituitary tumor-transforming gene (PTTG) was only recently discovered. Its overexpression occurs in a wide variety of endocrine and non-endocrine tumors, including ones of pituitary, thyroid, ovary, breast, prostate, lung, esophagus, colon, and the central nervous system. It affects tumor invasiveness and recurrence in several systems, functions as a securin during cell cycle progression, and inhibits premature sister chromatid separation. PTTG is involved in multiple cellular pathways, including proliferation, DNA repair, transformation, angiogenesis induction, invasion, and the induction of genetic instability. In thyroid carcinomas, PTTG expression is a marker of invasiveness. PTTG is overexpressed in most pituitary adenomas, where it appears to correlate with recurrence and angiogenesis. Increasing evidence also points to the role of PTTG in endocrine organ development. For example, PTTG knockout mice show defective pancreatic b-cell proliferation. Herein, we review the current knowledge regarding PTTG-mediated pathways based on evidence from in vivo and in vitro studies as well as knockout mice models. We also summarize the issue of PTTG expression and its correlation with clinicopathologic parameters in patients with neoplasms, particularly of endocrine organs. In addition, we discuss in vitro and in vivo therapeutic models targeting PTTG overexpression.

show abstract

“…These mice also develop organ-specific abnormal cell nuclear morphology, such as macronuclei in the pancreatic b-cells and the hepatocytes (Wang et al 2003, Akino et al 2005. Pancreatic b-cell proliferation is slower and islet size is much smaller than wild-type (WT) in both male and female PTTGK/K mice, but only male mice develop overt diabetes apparently due to lower insulin sensitivity (Wang et al 2003, Fraenkel et al 2006. b-Cell apoptosis appears normal in PTTGK/K mice (Wang et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Murine pituitary tumor-transforming gene functions as a securin protein in insulin-secreting cells

Yu¹,

Cruz²,

Calzi³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

Human pituitary tumor-transforming gene 1 (PTTG1) encodes a securin protein critically important in regulating chromosome separation. Murine PTTG (mPTTG) is 66% homologous to human PTTG1 and PTTG-null (PTTGK/K) mice exhibit pancreatic b-cell hypoplasia and abnormal nuclear morphology with resultant diabetes. As we show that ductal b-cell neogenesis is intact in PTTGK/K mice, we explored mechanism for defective b-cell replication. We tested whether mPTTG exhibits securin properties in mouse insulin-secreting insulinoma MIN6 cells, using a live-cell system to monitor mitosis in cells transfected with an enhanced green fluorescent protein (EGFP)-tagged mPTTG conjugate (mPTTG-EGFP). To fulfill the criteria for securin properties, the protein should undergo degradation immediately before the metaphaseto-anaphase transition when expression levels are low, and should inhibit metaphase-to-anaphase transition when expression levels are high. EGFP itself did not undergo degradation throughout mitosis and high levels of EGFP per se did not affect normal mitosis progression (nZ25). However, mPTTG-EGFP was degraded 2 min before the metaphaseto-anaphase transition when expression levels were low (nZ19), and high mPTTG-EGFP levels blocked metaphaseto-anaphase transition in 13 cells. mPTTG-EGFP inhibited MIN6 cell proliferation and caused apoptosis. Immunocoprecipitation demonstrated binding of mPTTG-EGFP and separase. These results show that mPTTG exhibits properties consistent with a murine securin in insulin-secreting mouse cells and mPTTG overexpression inhibits cell proliferation, suggesting that defective b-cell proliferation observed in PTTGK/K mice is likely due to abnormal cell-cycle progression.

show abstract

Sex-steroid milieu determines diabetes rescue in pttg-null mice

Cited by 18 publications

References 53 publications

Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity

Metabolic and behavioral responses to high-fat feeding in mice selectively bred for high wheel-running activity

Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update

Murine pituitary tumor-transforming gene functions as a securin protein in insulin-secreting cells

Contact Info

Product

Resources

About