Amiloride derivatives enhance insulin release in pancreatic islets from diabetic mice

BACKGROUND: Amiloride derivatives, commonly used for their diuretic and antihypertensive properties, can also cause a sustained but reversible decrease of intracellular pH (pH(i)). Using dimethyl amiloride (DMA) on normal rodent pancreatic islets, we previously demonstrated the critical influence of islet pH(i )on insulin secretion. Nutrient-stimulated insulin secretion (NSIS) requires a specific pH(i)-range, and is dramatically enhanced by forced intracellular acidification with DMA. Furthermore, DMA can enable certain non-secretagogues to stimulate insulin secretion, and induce time-dependent potentiation (TDP) of insulin release in mouse islets where this function is normally absent. The present study was performed to determine whether pH(i)-manipulation could correct the secretory defect in islets isolated from mice with type 2 diabetes. METHODS: Using two mouse models of type 2 diabetes, we compared a) pHi-regulation, and b) NSIS with and without treatment with amiloride derivatives, in islets isolated from diabetic mice and wild type mice. RESULTS: A majority of the islets from the diabetic mice showed a slightly elevated basal pH(i )and/or poor recovery from acid/base load. DMA treatment produced a significant increase of NSIS in islets from the diabetic models. DMA also enabled glucose to induce TDP in the islets from diabetic mice, albeit to a lesser degree than in normal islets. CONCLUSION: Islets from diabetic mice show some mis-regulation of intracellular pH, and their secretory capacity is consistently enhanced by DMA/amiloride. Thus, amiloride derivatives show promise as potential therapeutic agents for type 2 diabetes

The Effect of Ciprofloxacin on the Pharmacokinetic and ECG Parameters of Quinidine

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97168/1/j.1552-4604.1990.tb03570.x.pd

Heterogeneity of tissue dehydrogenases

Rat tissue homogenates have been subjected to zone electrophoresis in starch gel. Lactate, malate, isocitrate, glucose 6-phosphate and [alpha]-glycerophosphate dehydrogenase activity was directly visualized by incubating the gel strips in solutions containing a specific substrate, a tetrazolium salt, methylene blue and the appropriate pyridine nucleotide. Electrophoretic heterogeneity of some of the dehydrogenases was observed in material from different organs. A similar multiplicity of components in some specific dehydrogenases was also demonstrated in cytologically homogeneous material including cells grown by tissue culture techniques. Significance of this multiplicity of enzymes is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32402/1/0000477.pd

Phenobarbital-Induced Increases in Methylation of Ribosomal Precursor Ribonucleic Acid

SUMMARY SMITH, STEVE

The Seminole Indians of Florida: Morphology and serology

The Seminole Indians of Florida were studied on their three reservations for blood types, red cell enzymes, serum proteins, physical measurements, and relationships. Both serologic and morphologic factors suggest their close similarity to other Indians and small amount of admixture. The Florida Seminoles are similar to Cherokee “full-bloods” in their absence of Rho and their incidence of O and M. In the presence of Di a they are similar to other Indians, especially those of South America. While the presence of G-6-P-D A and the frequency of Hgb. S are indicative of Negro ancestry, the absence of Rho suggests that the Negro contribution must have been small. Physical traits give parallel results. Both serology and morphology further show that the Seminoles of the Dania and Big Cypress reservations are more similar to each other than to those of the Brighton reservation, in keeping with their history.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37497/1/1330320109_ftp.pd