Influence of the expression of parathyroid hormone 1 receptor to INS-1 cell function under high glucose condition / 中华内分泌代谢杂志

Objective To observe insulin synthesis and secretion in INS-1 under high glucose, and to clarify the effect of PTH1R. Methods After successful construction of recombinant PTH1R-siRNA vectors in INS-1 cell, insulin secretion and intracellular insulin content of control group, siPTH1R-Negative control group, PTHrP group, and siPTH1R group under 25 mmol/L glucose were measured by radioimmunoassay in INS-1 cell. Intracellular calcium were detected by Fluo-3/AM and the capability of glucose transport was calculated by assaying the uptake of [3H]-2-deoxy-D-glucose in cells.Results Compared with control group, and siPTH1R-NC group, PTHrP group showed increased capability of insulin secretion; PTHrP group had higher intracellular insulin levels than others; PTHrP group showed increased intracellular calcium; the uptake of [3H]-2-deoxy-D-glucose under high glucose after 48h of PTHrP group was increased(all P＜0.01). Conclusion There is a close relationship between PTH1R activation and insulin secretion and synthesis, PTH1R activation may be one of the protective mechanisms in maintaining function of β-cell under high glucose.

Structure and Function of a Minimal Receptor Activation Domain of Parathyroid Hormone

The structure and function of short-length amino terminal PTH analogues were studied. The substitution of Leu7 with Phe in [Ala3, 10Leu7Arg11]rPTH (1-11) NH2 analogue peptides did not show any reduction in cAMP formation. Replacement of the 1st, 7th and 8th residues revealed different activities, depending upon the residue type. The substitution of Ala1 by Ser in [Ala3, 10Leu7Arg11]rPTH (1-11) NH2 caused nearly a complete loss of cAMP formation. Meanwhile, NMR analysis of [ (Ala1/ Ser1) Ala3, 10 (Leu7/Phe7) Arg11]rPTH (1-11) NH2 revealed an alpha- helical backbone structure with a flexible conformation at the carboxyl-terminus. The overall results suggest that 11-residue short oligopeptide analogues of PTH tend to form an alpha-helical structure and the different activities of those analogues could be associated with residue specificity rather than the secondary conformational structure.

Study on gene expression of PTH/PTHrP receptor in patients with renal impairment / 中华肾脏病杂志

Objective To investigate the changes of parathyroid hormone receptor in patients with different stages of renal disease and its possible underlying mechanisms. Methods Relatively quantitative RT/PCR method was used to detect PTH receptor mRNA expression in renal specimens obtained through biopsy or operation. Results The levels of PTH receptor mRNA were significantly decreased in all patients with chronic glomerulonephritisx moderate renal failure severe renal failure and acute renal failure, which was correlated with the extent of renal impairment. Conclusion The downregulation of renal PTH receptor occurs much earlier than the changes of renal function., plasma PTH., serum phosphate and calcium in the course of human renal disease.