Hypoglycemia has for the most part been studied inadequately for both of the commonly used long-acting insulin analogs in type 1 and type 2 diabetes. Almost all existing trials have been designed to investigate changes in glycemic control and not differences in hypoglycemia events. In this review, we present an overview of the hypoglycemic data available from the randomized controlled trials comparing insulin glargine and insulin detemir with NPH or continuous subcutaneous insulin infusion in type 1 and type 2 diabetes. The limited head-to-head glargine versus detemir data are also discussed with comments on early results relating to the newer insulin analog, degludec. Basal insulin analogs are associated with reduced nocturnal hypoglycemia in both type 1 and type 2 diabetes. Most studies have excluded participants with impaired awareness of hypoglycemia or previous severe events, however, and hypoglycemia reporting is variable and inconsistent. This limits interpretation for those with long-duration type 1 diabetes, and particularly impaired awareness of hypoglycemia, or long-duration more insulin-deficient type 2 diabetes. New optimally designed studies are required to elucidate the true impact of basal analogs on hypoglycemia burden in those living with long-term insulin therapy.

2006-09-01·Cardiovascular Drug Reviews

The Many Faces of H89: A Review

Review

作者: A. Lochner ; J. A. Moolman

ABSTRACTH89 is marketed as a selective and potent inhibitor of protein kinase A (PKA). Since its discovery, it has been used extensively for evaluation of the role of PKA in the heart, osteoblasts, hepatocytes, smooth muscle cells, neuronal tissue, epithelial cells, etc. Despite the frequent use of H89, its mode of specific inhibition of PKA is still not completely understood. It has also been shown that H89 inhibits at least 8 other kinases, while having a relatively large number of PKA‐independent effects which may seriously compromise interpretation of data.Thus, while recognizing its kinase inhibiting properties, it is advised that H89 should not be used as the single source of evidence of PKA involvement. H‐89 should be used in conjunction with other PKA inhibitors, such as Rp‐cAMPS or PKA analogs.

2001-05-01·American Journal of Physiology-Cell Physiology3区 · 生物学

Increased functional cell surface expression of CFTR and ΔF508-CFTR by the anthracycline doxorubicin

3区 · 生物学

Article

作者: Shaw, Collin M. ; Hamilton, Joshua W. ; Stanton, Bruce A. ; Maitra, Rangan

Cystic fibrosis (CF) is a disease that is caused by mutations within the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most common mutation, ΔF508, accounts for 70% of all CF alleles and results in a protein that is defective in folding and trafficking to the cell surface. However, ΔF508-CFTR is functional when properly localized. We report that a single, noncytotoxic dose of the anthracycline doxorubicin (Dox, 0.25 μM) significantly increased total cellular CFTR protein expression, cell surface CFTR protein expression, and CFTR-associated chloride secretion in cultured T84 epithelial cells. Dox treatment also increased ΔF508-CFTR cell surface expression and ΔF508-CFTR-associated chloride secretion in stably transfected Madin-Darby canine kidney cells. These results suggest that anthracycline analogs may be useful for the clinical treatment of CF.

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