Neonatal rats receiving streptozotocin at birth resulted in an acute but transient hyperglycemia for about ten days. This early transient hyperglycemic condition led to a reduced body weight gain in the suckling period but body weights were normalized by day 42. Streptozotocin pups had higher pancreatic wet weights and pancreatic protein and DNA contents at day 16 as compared to control pups, but not thereafter. At day 16, pancreatic trypsinogen in streptozotocin pups showed a transient increase over control pups but amylase and lipase were similar in the two groups. No difference was observed between the streptozotocin pups and the control group in their pancreatic lipase and trypsinogen concentrations after 16 days. In contrast, pancreatic amylase concentrations were lower in streptozotocin pups from day 18 to day 42 but the difference between the groups was significant only from days 18 to 24. Insulin supplementation of streptozotocin pups for four days in the neonatal period restored the pancreatic amylase concentration to the control level at days 18 and 20. These results indicate that acute streptozotocin administration at birth to neonates affects subsequent exocrine pancreatic development, particularly that of amylase, and that exogenous insulin attenuated the effect.

Amylases↗

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Caring the On Lok way.

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Aged↗

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Group B streptococcus and pregnancy: update and recommendations.

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Adult↗

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Neonatal group B streptococcal disease.

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Algorithms↗

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Activated c-Met signals through PI3K with dramatic effects on cytoskeletal functions in small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive illness with early metastases. There are several receptor tyrosine kinases (RTKs) overexpressed in SCLC, including c-Met. c-Met contains an external semaphorin-like domain, a cytoplasmic juxtamembrane domain, tyrosine kinase domain and multiple tyrosines that bind to adapter molecules. We have previously reported that c-Met is abundantly expressed in the NCI-H69 SCLC cell line and now have determined the downstream effects of stimulating c-Met via its ligand hepatocyte growth factor (HGF). Utilizing unique phospho-specific antibodies generated against various tyrosines of c-Met, we show that Y1003 (binding site for c-Cbl and a negative regulatory site), Y1313 (binding site for PI3K), Y1230/Y1234/Y1235 (autophosphorylation site), Y1349 (binding site for Grb2), Y1365 (important in cell morphogenesis) are phosphorylated in response to HGF (40 ng/ml, 7.5 min) in H69 cells. Since multiple biological and biochemical effects are transduced through the PI3K pathway, we determine the role of PI3K in the c-Met/HGF stimulation pathway. We initially determined that by inhibiting PI3K with LY294002 (50 microM over 72 hours), there was at least a 55% decrease in viability of H69 cells. Since H69 SCLC cells form clusters in cell culture, we determined the effects of HGF and LY294002 on cell motility of the clusters by time-lapse video microscopy. In response to HGF, SCLC moved much faster and formed more clusters, and this was inhibited by LY294002. Finally, we determined the downstream signal transduction of HGF stimulation of c-Met with and without inhibition of c-Met (with geldanamycin, an anisamycin antibiotic that inhibits c-Met in SCLC) or PI3K (with LY294002). We show that association of c-Met with PI3K and GAB2 is diminished by inhibiting c-Met. In summary, activation of the c-Met pathway targets the PI3K pathway in SCLC and this may be an important therapeutic target.

Adaptor Proteins, Signal Transducing↗

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