Searchable abstracts of presentations at key conferences in endocrinology

ea0004dp11 | Diabetes, metabolism and cardiovascular | SFE2002

PPARalpha activation during late pregnancy improves insulin action and attenuates glucose-stimulated insulin hypersecretion

Smith N , Greenwood G , Sugden M , Holness M

Lipid sensing by pancreatic beta cells is co-ordinated through the expression and activity of peroxisome proliferator-activated receptors (PPARs). Through their action to lower triacylglycerol delivery to peripheral tissues, PPARalpha activators also oppose insulin resistance by relieving inhibition of insulin-stimulated glucose disposal. Mid to late pregnancy is an insulin-resistant state associated with hypertriglyceridaemia. We investigated regulatory interactions between P...

ea0004dp12 | Diabetes, metabolism and cardiovascular | SFE2002

Activation of peroxisome-proliferator-activated receptor (PPAR) alpha reverses high-fat induced insulin hypersecretion in perifused pancreatic islets

Greenwood G , Smith N , Holness M , Sugden M

Activation of PPARalpha pharmacologically by WY14,643 enhances insulin sensitivity in insulin-resistant high-fat-fed rats. PPARalpha is expressed in pancreatic islets, where it affects genes involved in lipid metabolism. We investigated effects of PPARalpha activation by WY14,643 on glucose-stimulated insulin secretion (GSIS) in a rat model of high-fat feeding in which insulin resistance is observed in conjunction with compensatory insulin hypersecretion. To identify persisten...

ea0002p28 | Diabetes and metabolism | SFE2001

Glucocorticoid excess leads to redistribution of available pyruvate from oxidation to maintain a normal rate of lactate formation via up-regulation of skeletal-muscle pyruvate dehydrogenase kinase 4 expression

Holness M , Bulmer K , Smith N , Sugden M

Insulin resistance is an established consequence of glucocorticoid excess. In rats, administration of the synthetic glucocorticoid dexamethasone decreases the sensitivity of glucose oxidation to insulin in soleus muscle strips, but sensitivity of lactate formation is unimpaired. In rats, cortisol impairs pyruvate tolerance and, in man, dexamethasone decreases whole-body glucose oxidation. The present study explored possible mechanisms that might underlie these effects. Activat...

ea0029p553 | Diabetes | ICEECE2012

New fast and reversible leptin antagonist-induced mice model of metabolic syndrome and T2DM

Solomon G , Monsonego-Ornan E , Chapnik N , Smith E , Froy O , D'Alessio D , Gertler A

Obesity and its major consequence, type II diabetes mellitus (T2DM), is epidemic throughout Western society. T2DM accounts for 95% of the diabetes worldwide. One limitation to the development of new diabetes treatments has been a lack of effective animal models to use in research. There are no rodent models that recapitulate the pancreatic β-cell lesions of humans with T2DM. Moreover, animal models of obesity either require overfeeding which is expensive and takes weeks t...

ea0004s18 | Maintenance of pregnancy | SFE2002

Cell biology of embryo-implantation: unravelling the role of leukaemia inhibitory factor

Fouladi|#Nashta A , Schofield G , Andreu C , Nijjar N , Smith A , Heath J , Kimber S

Many of the functions of ovarian steroids in regulating embryo-implantation occur through the actions of cytokines and growth factors on the uterus. One such cytokine, Leukaemia Inhibitory factor (LIF), is critical for implantation in a range of mammalian species. LIF is expressed transiently in the murine glandular uterine epithelium (GE) on day 1 and then day 4 of pregnancy (day of implantation) induced by estrogen. Female mice lacking a functional LIF gene cannot support em...

ea0029p1783 | Thyroid cancer | ICEECE2012

Regulation of hPTTG expression and phosphorylation: autocrine interactions with growth factors in thyroid cells

Lewy G. , Ryan G. , Read M. , Fong J. , Seed R. , Sharma N. , Smith V. , Kwan P. , Stewart S. , Warfield A. , Melmed S. , Eggo M. , Franklyn J. , McCabe C. , Boelaert K.

Introduction: The human Pituitary Tumor Transforming Gene (hPTTG) is a phosphorylated proto-oncogene induced in multiple tumour types. hPTTG phosphorylation is mediated by cyclin-dependent kinase 2 (CDC2) and expression is regulated by specificity protein 1 (SP1). In thyroid cancer, hPTTG induces genetic instability and propagates growth through induction of growth factors (GFs).Methods: The interplay between hPTTG phosphorylation, SP1 regulation and GF ...