No abstract

ObjectivePituitary stalk interruption syndrome (PSIS) is characterized by the absence of pituitary stalk, pituitary hypoplasia, and ectopic posterior pituitary. Due to the rarity of PSIS, clinical data are limited, especially in Chinese people. Herein, we analyzed the clinical characteristics of patients diagnosed with PSIS from our center over 10 years.Patients and MethodsWe retrospectively analyzed the clinical manifestations and laboratory and MRI findings in 55 patients with PSIS.ResultsOf the 55 patients with PSIS, 48 (87.3%) were male. The average age was 19.7±6.7 years and there was no familial case. A history of breech delivery was documented in 40 of 45 patients (88.9%) and 19 of 55 patients (34.5%) had a history of dystocia. Short stature was found in 47 of 55 patients (85.5%) and bone age delayed 7.26±5.37 years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone, gonadotropins, corticotropin, and thyrotropin were 100%, 95.8%, 81.8%, 76.3%, respectively. Hyperprolactinemia was found in 36.4% of patients. Three or more pituitary hormone deficiencies were found in 92.7% of the patients. All patients had normal posterior pituitary function and absent pituitary stalk on imaging. The average height of anterior pituitary was 28 mm, documented anterior pituitary hypoplasia. Midline abnormalities were presented in 9.1% of patients.ConclusionsThe clinical features of our Chinese PSIS patients seem to be different from other reported patients in regarding to the higher degree of hypopituitarism and lower prevalence of midline defects. In addition, our patients were older at the time of case detection and the bone age was markedly delayed. We also had no cases of familial PSIS.

Abstract. Endoplasmic reticulum (ER) stress and autophagy have both been reported to be associated with lipotoxicity in β-cells, yet the relationship between them has not been fully clarified. In the present study, we tested the hypothesis that the ER stress-autophagic pathway in β-cells is a downstream pathway activated following saturated fatty acid treatment. Mouse insulinoma (MIN6) β-cells were treated with either palmitate or thapsigargin (TG) with or without various inhibitors. The results indicated that palmitate strongly enhanced the protein expression of microtubule-associated protein 1 light chain 3 (LC3)-II. Furthermore, the expression levels of ER stress markers, BiP and CHOP, and phosphorylation levels of JNK were increased after palmitate treatment. In addition, palmitate-induced autophagy was blocked by 500 µM of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or 20 µM JNK inhibitor SP600125. In turn, the phosphorylation of Akt (Ser473) was also downregulated by palmitate, while the levels of insulin receptor β (IRβ) were not reduced. A further increase in LC3-II levels was observed in cells treated with both palmitate and 50 µM PI3K/Akt inhibitor LY294002 compared with cells treated with palmitate alone. Palmitate-induced phospho-Akt (Ser473) downregulation was also inhibited by TUDCA or SP600125. Pretreatment with the autophagy inhibitor 3-methyladenine (3-MA, 5 mM) for 1 h increased the expression of ER stress markers, and enhanced cell injuries caused by 0.1 µM TG, including decreased cell viability and insulin secretion. Palmitate induces autophagy in pancreatic β-cells possibly through activation of ER stress and its downstream JNK pathway. Palmitate-induced autophagy may protect β-cells against cell injuries caused by ER stress. IntroductionCell dysfunction induced by lipid accumulation or lipotoxicity in pancreatic β-cells may contribute to the pathogenesis of type 2 diabetes. In recent years, autophagy has been identified as a novel mechanism that regulates β-cell function (1-3) and death (4-6). Autophagy is a conserved self-digestion process among eukaryotes that regulates cellular component degradation through lysosomes. Autophagy plays an important role in maintaining cell homeostasis by regulating the synthesis, degradation and recycling of cellular components (7). A low level of constitutive autophagy exists in order to control the quality of proteins and organelles. Autophagy is important for survival as it reallocates nutrients to essential processes from less important ones (8). In addition, autophagy can also be induced under stress conditions to maintain the balance of the cell. Growing evidence (4,9) indicates that autophagy in β-cells is activated by free fatty acids, and suggests that addressing the underlying mechanisms involved in lipid-induced autophagy may provide clues for treating or preventing β-cell lipotoxicity.Free fatty acids are known as inducers of endoplasmic reticulum (ER) stress. Previous evidence has revealed that saturated fatty acid induces β-cell...

Glucagon-like peptide-1 (GLP-1) receptor plays an essential role in regulating glucose metabolism. GLP-1 receptor agonists have been widely used for treating diabetes and other insulin resistance-related diseases. However, mechanisms underlying the anti-diabetic effects of GLP-1 receptor agonists remain largely unknown. In this study, we investigated the effects of GLP-1 agonist exendin-4 on the expression of adiponectin, an insulin sensitizing hormone. We found that exendin-4 increased the expression and secretion of adiponectin both in vitro and in vivo. Our data showed that exendin-4 upregulated adiponectin expression at both mRNA and protein levels in adipocytes and adipose tissues. The effects of exendin-4 on adiponectin expression were dependent on the GLP-1 receptor. We further demonstrated important roles of Sirt1 and transcriptional factor Foxo-1 in mediating the function of exendin-4 in regulating adiponectin expression. Suppression of Sirt1 or Foxo-1 expression significantly impaired exendin-4-induced adiponectin expression. Consistently, exendin-4 up-regulated Sirt1 and Foxo-1 expression in vivo. Our work is the first study demonstrating the role of Sirt1/Foxo-1 in regulating the regulatory function of a GLP-1 receptor agonist in adiponectin expression both in vitro and in vivo. The results provide important information for the mechanism underlying the function of GLP-1R on improving insulin resistance and related diseases.

Compared with NPS, PSIS patients had more severe anterior pituitary hormone deficiency, lower anterior pituitary hormone secretion and higher probability of abnormal pituitary morphology. HESX1, LHX4 and SOX3 polymorphisms may be associated with PSIS.