Pancreatic secretion and plasma levels of cholecystokinin-33/39 (CCK) were measured for 5 h after a meal in dogs with and without exclusion of pancreatic juice. Significant and prolonged increases in pancreatic secretion and plasma CCK levels were observed irrespective of pancreatic juice exclusion. The integrated responses of pancreatic protein output (2.6 +/- 0.6 g/300 min), plasma CCK (1.3 +/- 0.5 nmol.l-1 .300 min) with exclusion of pancreatic juice showed no significant differences from those without exclusion (2.8 +/- 0.3 g/300 min and 1.3 +/- 0.3 nmol.l-1.300 min for protein output and CCK, respectively). These results suggest that the CCK-mediated feedback mechanism of pancreatic enzyme secretion does not work, at least not in the postprandial state in dogs.
An ultramicro method is described for the determination of peptides by high performance liquid chromatography with coulometric detection. The method is based on the formation of electrochemically oxidizable copper(I) ion by reaction of peptides with copper(II) ion in an alkaline medium containing ammonia in postcolumn reaction. Di-and tripeptides used as model compounds (6 species) are separated on a reversed phase column . The detection limit was 200 pg for glycylglycylglycine. Prolylglycine was detected, but not glycylproline, which has no amide-bond in the molecule.
Background
Diabetic nephropathy (DN) involves various structural and functional changes because of chronic glycemic assault and kidney failure. Proteinuria is an early clinical manifestation of DN, but the associated pathogenesis remains elusive. This study aimed to investigate the role of microtubule associated protein 4 (MAP4) phosphorylation (p-MAP4) in proteinuria in DN and its possible mechanisms.
Methods
In this study, the urine samples of diabetic patients and kidney tissues of streptozotocin (STZ)-induced diabetic mice were obtained to detect changes of microtubule associated protein 4 (MAP4) phosphorylation. A murine model of hyperphosphorylated MAP4 was established to examine the effect of MAP4 phosphorylation in DN. Podocyte was applied to explore changes of kidney phenotypes and potential mechanisms with multiple methods.
Results
Our results demonstrated elevated content of p-MAP4 in diabetic patients’ urine samples, and increased kidney p-MAP4 in streptozocin (STZ)-induced diabetic mice. Moreover, p-MAP4 triggered proteinuria with aging in mice, and induced epithelial-to-mesenchymal transition (EMT) and apoptosis in podocytes. Additionally, p-MAP4 mice were much more susceptible to STZ treatment and showed robust DN pathology as compared to wild-type mice. In vitro study revealed high glucose (HG) triggered elevation of p-MAP4, rearrangement of microtubules and F-actin filaments with enhanced cell permeability, accompanied with dedifferentiation and apoptosis of podocytes. These effects were significantly reinforced by MAP4 hyperphosphorylation, and were rectified by MAP4 dephosphorylation. Notably, pretreatment of p38/MAPK inhibitor SB203580 reinstated all HG-induced pathological alterations.
Conclusions
The findings indicated a novel role for p-MAP4 in causing proteinuria in DN. Our results indicated the therapeutic potential of MAP4 in protecting against proteinuria and related diseases.
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