1.
DLK1, Notch Signaling and the Timing of Puberty.
Macedo, DB, Kaiser, UB
Seminars in reproductive medicine. 2019;(4):174-181
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Abstract
The factors that trigger human puberty are among the central mysteries of reproductive biology. Several approaches, including mutational analysis of candidate genes, large-scale genome-wide association studies, whole exome sequencing, and whole genome sequencing have been performed in attempts to identify novel genetic factors that modulate the human hypothalamic-pituitary-gonadal axis to result in premature sexual development. Genetic abnormalities involving excitatory and inhibitory pathways regulating gonadotropin-releasing hormone secretion, represented by the kisspeptin (KISS1 and KISS1R) and makorin ring finger 3 (MKRN3) systems, respectively, have been associated with sporadic and familial cases of central precocious puberty (CPP). More recently, paternally inherited genetic defects of DLK1 were identified in four families with nonsyndromic CPP and a metabolic phenotype. DLK1 encodes a transmembrane protein that is important for adipose tissue homeostasis and neurogenesis and is located in the imprinted chromosome 14q32 region associated with Temple syndrome. In this review, we highlight the clinical and genetic features of patients with CPP caused by DLK1 mutations and explore the involvement of Notch signaling and DLK1 in the control of pubertal onset.
2.
Saxagliptin Upregulates Nesfatin-1 Secretion and Ameliorates Insulin Resistance and Metabolic Profiles in Type 2 Diabetes Mellitus.
Chen, K, Zhuo, T, Wang, J, Mei, Q
Metabolic syndrome and related disorders. 2018;(7):336-341
Abstract
BACKGROUND AND AIMS Saxagliptin as one of dipeptidyl peptidase-4 (DPP-4) inhibitors can effectively improve glycaemic control in type 2 diabetes mellitus, and nesfatin-1 is regarded as a very important factor in regulating feeding behavior and energy homeostasis. In this trial, we observed the effect of saxagliptin on regulating nesfatin-1 secretion and ameliorating insulin resistance and metabolic profiles in type 2 diabetes mellitus. METHODS One hundred two type 2 diabetes participants (M/F = 48/54) were investigated. Fifty-one (M/F = 24/27) of them as the treatment group were treated with oral glucose-lowering agents including saxagliptin, the other 51 (M/F = 24/27) as the control group were treated with oral glucose-lowering agents excluding any DPP-4 inhibitors. The parameters of serum nesfatin-1, C-peptide, homeostasis model assessment-β (HOMA-β) function, HOMA insulin resistance (HOMA-IR), glycosylated hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), and blood pressure (BP) at baseline, month 3, 6, and 12 were observed and compared respectively. RESULTS Saxagliptin significantly upregulated nesfatin-1 secretion (P < 0.001 at 3-, 6-, and 12-months vs. baseline), increased serum C-peptide (P < 0.05, 0.001, and 0.001 at 3-, 6-, and 12-months vs. baseline), improved HOMA-IR and function of HOMA-β (P < 0.001 at 3-, 6-, and 12-months vs. baseline) and metabolic profiles (P < 0.001 with HbA1c at 3-, 6- and 12-months; P < 0.001 with LDL-C at 6- and 12-months; P < 0.001 and 0.01 with HDL-C at 6- and 12-months vs. baseline), declined BMI (P < 0.05 at 6- and 12-months vs. baseline) and BP (P < 0.001 with systolic BP (SBP), and mean BP at 6- and 12-months, P < 0.01 with diastolic BP at 6- and 12-months vs. baseline). CONCLUSIONS Saxagliptin could upregulate nesfatin-1 secretion and ameliorate insulin resistance and metabolic profiles in type 2 diabetes mellitus. Saxagliptin had the potential to play fundamental by upregulating nesfatin-1 secretion besides lowering glucose by inhibiting the degradation of glucagon-like peptide-1.
3.
New developments in our understanding of DISH (diffuse idiopathic skeletal hyperostosis).
Sarzi-Puttini, P, Atzeni, F
Current opinion in rheumatology. 2004;(3):287-92
Abstract
PURPOSE OF REVIEW Diffuse idiopathic skeletal hyperostosis (DISH) or Forestier's disease is a common disorder among older adults. The diagnosis is based solely on radiographic abnormalities defined using the Resnick criteria. DISH is characterized by ossification of the anterior longitudinal ligament of the spine and various extraspinal ligaments. DISH often coexists with OA, but patients affected by this disorder differ from patients with primary OA in several aspects: prevalence in the general population, gender distribution, anatomic site of primary involvement, magnitude and distribution in the spine and the peripheral joints. Purpose of this review is to summarize new clinical, pathogenetic and therapeutic insights of this disease. RECENT FINDINGS Recent studies confirm that patients with DISH have a greater body mass index, higher serum uric acid levels and are more likely to have diabetes mellitus. In addition, DISH is most probably related to abnormal bone cell growth/activity reflecting the influence of metabolic factors that lead to new bone formation. Serum matrix Gla protein may be a marker of osteometabolic syndromes, such as DISH, that cause hyperostosis. SUMMARY Many recent developments of DISH are described in this review. Possible pathogenetic mechanism driving bone deposition are discussed. DISH is still recognized radiographically; no specific drug has been yet identified.