These results highlight the predominant involvement of S100 proteins in the host response during periodontitis, identify host defence components that have not been linked previously to this disease and suggest new potential biomarkers for monitoring disease activity in periodontitis.
We describe a new, simple, robust and efficient method based on direct-tissue matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry that enables consistent semi-quantitation of peptide hormones in isolated pancreatic islets from normal and diabetic rodents. Prominent signals were measured that corresponded to all the main peptide hormones present in islet-endocrine cells: (α-cells) glucagon, glicentin-related polypeptide/GRPP; (β-cells) insulin I, insulin II, C-peptide I, C-peptide II, amylin; (δ-cells) somatostatin-14; and (PP-cells), and pancreatic polypeptide. The signal ratios coincided with known relative hormone abundances. The method demonstrated that severe insulin deficiency is accompanied by elevated levels of all non-β-cell-hormones in diabetic rat islets, consistent with alleviation of paracrine suppression of hormone production by non-β-cells. It was also effective in characterizing hormonal phenotype in hemizygous human-amylin transgenic mice that express human and mouse amylin in approx. equimolar quantities. Finally, the method demonstrated utility in basic peptide-hormone discovery by identifying a prominent new Gcg-gene-derived peptide (theoretical monoisotopic molecular weight 3263.5 Da), closely related to but distinct from GRPP, in diabetic islets. This peptide, whose sequence is HAPQDTEENARSFPASQTEPLEDPNQINE in Rattus norvegicus, could be a peptide hormone whose roles in physiology and metabolic disease warrant further investigation. This method provides a powerful new approach that could provide important new insights into the physiology and regulation of peptide hormones in islets and other endocrine tissues. It has potentially wide-ranging applications that encompass endocrinology, pharmacology, phenotypic analysis in genetic models of metabolic disease, and hormone discovery, and could also effectively limit the numbers of animals required for such studies.
Peptides derived from the glucagon gene Gcg, for example, glucagon and glucagon‐like peptide 1 (GLP‐1), act as physiological regulators of fuel metabolism and are thus of major interest in the pathogenesis of diseases, such as type‐2 diabetes and obesity, and their therapeutic management. Glicentin‐related pancreatic polypeptide (GRPP) is a further, 30 amino acid Gcg‐derived peptide identified in human, mouse, rat, and pig. However, the potential glucoregulatory function of this peptide is largely unknown. Here, we synthesized rat GRPP (rGRPP) and a closely related peptide, rat GRPP‐like peptide (rGRPP‐LP), and investigated their actions in the liver and pancreas of adult male rats by employing isolated‐perfused organ preparations. Rat GRPP and rGRPP‐LP did not affect glucose output from the liver, but both elicited potent inhibition of glucose‐stimulated insulin secretion (GSIS) from the rat pancreas. This action is unlikely to be mediated by glucagon or GLP‐1 receptors, as rGRPP and rGRPP‐LP did not stimulate cyclic adenosine monophosphate (cAMP) production from the glucagon or GLP‐1 receptors, nor did they antagonize glucagon‐ or GLP‐1‐stimulated cAMP‐production at either receptor. GRPP and GRPP‐LP may be novel regulators of insulin secretion, acting through an as‐yet undefined receptor.
1. The effect on renal function in sheep of inhibiting converting enzyme with captopril was examined before and after 5 days ACTH administration. 2. Glomerular filtration rate, effective renal plasma flow, effective renal blood flow, mean arterial pressure and plasma sodium were all significantly increased by ACTH treatment and plasma potassium was decreased. Captopril (20 mg i.v.) had no effect on renal function or blood pressure before or after ACTH treatment, although urinary potassium excretion decreased following captopril on day 6 of ACTH treatment. 3. The increase in glomerular filtration rate and effective renal plasma flow seen with ACTH treatment in sheep does not appear to be mediated by the reninangiotensin system.
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