Endocrine Abstracts

Background: The prevalence and incidence of type 2 diabetes are increasing around the world. Diabetes affects >230 million people worldwide and is expected to affect 350 million by 2025.Diabetes mellitus is a chronic disease that requires long-term medical attention. Type 2 diabetes was once called adult-onset diabetes. Now, because of the epidemic of obesity and inactivity, type 2 diabetes is occurring at younger ages. About 90% of patients who deve...

T2DM is expected to rise to 552 million by 2030. DM is associated with complications which result in reduced quality of life and premature mortality.T2DM has a long asymptomatic pre-clinical phase (~5–10 years) which frequently goes undetected. Benefits of early diagnosis on outcomes in screen-detected DM remain unclear. Some indirect evidence suggesting that early detection and intervention may be beneficial.Screening for DM ...

Diabetes (DM) is the leading cause of end-stage-renal disease (ESRD). Majority of T2DM patients (Pts) with ESRD need insulin. Kidneys play significant role in exogenous insulin metabolism. Chronic renal disease is associated with alterations in insulin metabolism and glycemic control. As renal function starts to decline, insulin requirement needs to be adjusted to reach euglycemia.A good metabolic control is not only important in the early phase of diabe...

Background: A functioning Hypothalamo-pituitary-adrenal (HPA) axis is essential for life. Prolonged high circulating levels of glucocorticoids inhibit pituitary Pro-opiomelanocortin (POMC) gene expression. Repression continues even in the absence of continued glucocorticoid exposure. To date there are no molecular explanations for this observation.Hypothesis: Long-term exposure to glucocorticoids causes de-novo DNA methylation of the pituit...

Introduction: Long-term repression of the HPA axis is a major side effect of chronic glucocorticoid administration, even after attempted withdrawal of therapy, and complicates management in patients. We have previously shown that the effect of chronic glucocorticoid treatment in vitro is in part mediated by inhibition of expression the POMC transcription factors Neuro D1 and Tpit, and that this is sustained on treatment withdrawal. We have now furth...

Introduction: POMC is activated in ACTH-dependent Cushing’s Syndrome. We have previously shown that RNA interference (RNAi) targeting POMC coding and promoter sequences induces silencing of POMC and a reduction in ACTH. We have modified our most potent exonic sequence with locked nucleic acid (LNA) chemistry. This is purported to increase serum stability. Here we test whether the LNA confers stability without compromising siRNA silencing potency.<...

Introduction: Pro-opiomelanocortin (POMC) is a precursor polypeptide which is cleaved to make adrenocorticotrophic hormone (ACTH) in the anterior pituitary. It is activated in Cushing’s disease. Current therapies for Cushing’s disease are inadequate. RNA interference (RNAi) allows highly specific and effective suppression of gene expression by use of short interfering RNAs (siRNAs).Method: In the current study we employed custom designed siRNAs...

Introduction: Although current medical therapies for acromegaly are highly effective, 30% of patients are left with inadequately controlled growth hormone (GH) levels. To investigate a novel therapeutic strategy we have used RNA interference (RNAi) to target GH coding and promoter sequences in vitro and assessed the effect on gene expression and DNA methylation.Method: A careful bioinformatics approach revealed only one area in the coding sequence...

Background: Proopiomelanocortin gene (POMC) and its cleaved product adrenocorticotrophin hormone (ACTH) play an important role in regulation of the hypothalamo-pituitary-adrenal (HPA) axis. ACTH stimulates the adrenal glands to release glucocorticoids. Glucocorticoid has a suppressive effect on ACTH and POMC. This suppression remains long after withdrawal, and may lead to adrenocortical insufficiency. POMC expression is dependent on the activities of some of the positively act...