Browsing by Subject "Diabetes Mellitus"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
Item Diabetes in Latinas : Depression, Metabolic Control, and the Roles of Acculturation and Social Support(2005-12-20) Olvera, Anna E.; Stewart, SunitaDiabetes is steadily becoming an epidemic among Latinos. This study sought to more fully understand the rarely studied population of Latinas with diabetes and the associations between and among diabetes, depression, social support, metabolic control and acculturation. Ninety-six participants from a large publicly funded teaching hospital's community clinic took part in a brief interview that involved demographic questions, a depression screening toll, a measure for Latino and non-Latino acculturation, and a measure to assess perceived social support. The participants agreed to share their most recent metabolic blood sugar reading. The results demonstrated high levels of depression in the urban Latina with diabetes. A high number of the participants met the criteria for likely depression (32.3%). A one-tailed Pearson correlation yielded a strong significant relationship between perceived social support and depression (r = -0.63, p = 0.00). Additionally, CES-D and a recent HbA1c reading (within six months of the interview) were determined to be significantly related (r(N = 80) = 0.20, p = .03). Exposure to U.S. culture measured in years correlated significantly with diagnosis of depression by a medical professional (rs = 0.22, p = 0.04). There was an additional finding that years of living with diabetes was significantly correlated with being considered depressed (CES-D score = 24; [rs = 0.23, p = 0.03]). These and other findings support possible interventions to improve the quality of health for Latinas at an urban publicly funded clinic.Item Molecular Imaging of αvβ6–Positive Tumors and Pancreatic β-Cell Mass by Radiolabeled Peptides(2011-02-01T19:35:51Z) Lin, Mai; Sun, XiankaiConventional diagnostic methodologies of lung cancer and diabetes are limited by sensitivity and specificity. In consequence, patients usually get diagnosed when the symptoms appear and the diseases are at the advanced stages. As the expressions of the avß6 integrin and glucagon-like peptide-1 receptor (GLP-1R) are highly related to aggressive tumor phenotypes and functional pancreatic ß-cells, this work has been set to develop peptide-based radiotracers that can specifically bind to avß6 or GLP-1R for noninvasively monitoring the progression of lung cancer and diabetes. By phage display, a peptide sequence that specific binds to avß6 was identified. In the evaluation of its truncated forms with similar binding affinity, a polyethylene glycol chain (PEG11) was inserted to the C-terminus and a bifunctional chelator (DOTA) was conjugated to either end of the peptides. The conjugates were labeled with 111In (t1/2: 2.8 d) under mild conditions with the highest achievable specific activity of 1.15 × 104 MBq/µmol. The in vivo evaluation was performed in a lung adenocarcinoma xenograft mouse model. Of the six conjugates, 10PD showed the best tissue contrast of the H2009 (avß6+) tumor. However, it also yielded to have the highest renal accumulation. The high kidney uptake of 10PD was found to be alleviated by conjugating DOTA at the N-terminus or reducing the peptide net charges. To evaluate GLP-1-based radiotracers for imaging pancreatic ß-cell mass (BCM), GLP-1, [D-Ala8]GLP-1, two bicyclic GLP-1 analogs (EM2196 and EM2198), and exendin-4 were synthesized and compared for their biological properties. All peptide constructs were tagged with an 6-aminohexanoic linker (Ahx) followed by DOTA conjugation at C-terminus and labeled with 64Cu (t1/2: 12.7 h). The specific activity of the labeled peptide conjugates was up to 1.0 × 106 MBq/µmol with radiochemical purity over 97%. Compared to GLP-1, [D-Ala8]GLP-1 revealed strong resistance against DPP-IV. In addition, EM2198 demonstrated high stability against NEP 24.11 presumably by the shielding effects from the two lactam bridges. All peptide conjugates were highly selective to the GLP-1R with the IC50 values in 0.1-0.4 nM. However, only 64Cu-EM2198 showed clear pancreas area on the microPET/CT studies. The signal of 64Cu-EM2198 from the pancreas was confirmed by the ex vivo imaging scans. The potential of 64Cu-EM2198 for imaging BCM was further supported by co-injecting a blocking dose of unlabeled exendin-4 and performing imaging studies in the STZ-treated diabetic mice.Item The Role of PTF1A in Spinal Cord Development(2006-05-15) Glasgow, Stacey Marie; Johnson, Jane E.Mutations in the human and mouse Ptf1a genes result in permanent diabetes mellitus and cerebellar agenesis. We show that PTF1a is present in precursors to GABAergic neurons in both the cerebellum and the spinal cord dorsal horn. A null mutation in Ptf1a reveals its requirement for the dorsal horn GABAergic neurons. Specifically, PTF1a is required for the generation of early born (dI4, E10.5) and late born (dILA, E12.5) dorsal interneuron populations identified by homeodomain factors Lhx1/5 and Pax2. Furthermore, in the absence of PTF1a, the dI4 dorsal interneurons trans-fate to dI5 (Lmx1b+), and the dILA to dILB (Lmx1b+;Tlx3+). This mis-specification of neurons results in a complete loss of inhibitory GABAergic neurons and an increase in the excitatory glutamatergic neurons in the dorsal horn of the spinal cord by E16.5. Thus, PTF1a function is an essential determinant for selecting the GABAergic over the glutamatergic neuronal cell fate in the developing spinal cord, and provides an important genetic link between inhibitory and excitatory interneuron development. Furthermore, Ptf1a appears to exert its functions within the neural tube, at least in part, as a component of a heterotrimeric complex composed of Ptf1a, E-protein, and Rbpsuh. Over-expression assays with Ptf1a and mutant forms of Ptf1a support a model in which the activity of Ptf1a is mediated by a balance between its participation in a trimeric complex, which includes Rbpsuh, and its participation as part of a heterodimer with E-proteins.Item The Roles of Orphan Nuclear Receptors in the Endocrine Pancreas(2008-09-12) Chuang, Jen-Chieh; Repa, Joyce J.The hormone insulin plays a critical role in carbohydrate metabolism of animals. The production and secretion of insulin by beta-cells of the pancreatic islet need to be tightly regulated to maintain proper blood glucose levels in the circulation. Dysfunction of this important endocrine system is responsible for diabetic mellitus. Over the last several years, research has suggested that the function and integrity of beta-cells can be dramatically affected by exposure to and accumulation of lipids. Several Orphan Nuclear Receptors (ONRs) have been identified and characterized in other cell types as "lipid sensors" that respond to elevated cellular lipid levels to regulate gene expression. Therefore the goal of my thesis research is to evaluate the expression and role of these transcription factors on beta-cell function and glucose metabolism. First, the complement of nuclear hormone receptors in mouse islets, and representative alpha- and beta- cell lines was determined by quantitative real-time PCR. Many nuclear receptors are expressed in the cells of the islet and several show differential expression levels under varying glucose conditions which suggests these nuclear receptors may be important for normal islet cell function. Of particular interest to our group LXRbeta, and to a lesser extent LXRalpha, are present in the beta cell of islets, and respond to synthetic LXR agonists to upregulate previously identified target genes. Exposing isolated mouse islets to the synthetic LXR agonist T1317 results in increased glucose-stimulated insulin secretion (GSIS). Incubation of islets from Lxr-null mice with this ligand has no effect on GSIS thus suggesting the T-compound effect is mediated by LXR. In addition, oral administration of T1317 to wild type, but not Lxr-null mice, altered islet GSIS in vivo and promoted efficient glucose clearance. These results suggest that activation of LXR in islet cells can modify islet function and help to control serum glucose levels. We also identified ChREBP as a novel target gene of LXR in the beta cells of the islet and characterized the importance of the LXR-ChREBP axis in insulin secretion from pancreatic islets. In addition to LXR, HNF4gamma is also an ONR of interest in beta cells. Realtime PCR results suggested that HNF4gamma and HNF4alpha are highly expressed in the pancreatic beta cells. Losing the function of HNF4alpha in beta cells has been shown to cause a rare form of diabetes called MODY1 (maturity-onset diabetes of the young).