Endocrine Abstracts

Mitochondria play a vital role in cellular bioenergetics, providing energy via oxidative phosphorylation (OXPHOS) and metabolic intermediates. Aerobic ATP production is orchestrated by a multi-enzyme complex, which uses the electrons gained during oxidation of energy substrates to generate an electrochemical potential across the mitochondrial (mt) membrane that drives ATP synthase. Although there is evidence that mitochondrial function as well as mtDNA mutations might play a r...

By a systematic approach we investigated the interaction of a selective number of GPCRs that are expressed in the arcuate nucleus and known to play an essential role in hypothalamic weight regulation. Based on the results of a sandwich ELISA and fluorescence resonance energy transfer (FRET) approach we report the interaction of the melanocortin three receptor (MC3R) and the growth hormone secretagogue receptor (GHSR) which are coexpressed on arcuate NPY/AgRP neurons. Fu...

Food intake is centrally regulated in hypothalamic nuclei. Peripheral hormonal signals activate their corresponding receptors in the arcuate nucleus (arc) and modulate the expression of pro-opiomelanocortin (POMC) and neuropetide Y (NPY)/agouti-related-protein (AgRP). Cleavage products of POMC stimulate melanocortin-4-receptors (MC4R) in the paraventricular nucleus (PVN) to inhibit food intake or stimulate MC3Rs in the arc to activate a feedback loop. Further mor...

Objective: The exopeptidase dipeptidyl peptidase 4 (Dpp4) selectively cleaves N-terminal dipeptides from several substrates, including cytokines, growth factors, neuropeptides, and the incretin hormones. The systemic inhibition of Dpp4 by the so-called gliptins (oral Dpp4 inhibitors) represents an effective and established treatment option for type 2 diabetes (T2D). In the current study we investigated in healthy as well as in obese and diabetic mice if a liver selective knock...

The use of more tissue-mimetic 3-dimensional (3D) cell culture models for in vitro drug screening has significantly increased in the past with the expectation to overcome with over-interpretation of drug effects obtained with conventional 2D cultures. In this study, we characterized 3D prostate cancer (PCa) organoids where PCa epithelial cells (LNCaP, DuCaP, LAPC4) were cultured alone or with PCa-associated fibroblasts (CAFs) in 96 well hanging drop plates in order to...

We have previously reported dominant negative missense mutations (P467L, V290M) in human PPAR gamma (peroxisome proliferator-activated receptor gamma) in association with severe insulin resistance, early onset type 2 diabetes and hypertension. In a large UK kindred, where the proband presented at age 15 years with severe insulin resistance (acanthosis nigricans, hyperinsulinaemia, PCOS), we have identified a novel heterozygous frameshift premature stop mutation in the PPAR gam...

Objective: A cytosine-adenine (CA)n microsatellite repeat polymorphism in the promoter region of the insulin-like growth factor-1 (IGF-1) gene has reported to be associated with IGF-1 serum levels, birth weight, body height, bone mineral density and risk for type 2 diabetes and myocardial infarction. Carriers and non-carriers of the most frequent allele (length 192 base pairs (bp)) showed significantly different total IGF-1 serum levels. This polymorphism may direct...