2011
The renin–angiotensin–aldosterone system and glucose homeostasis
Luther JM, Brown NJ. The renin–angiotensin–aldosterone system and glucose homeostasis. Trends In Pharmacological Sciences 2011, 32: 734-739. PMID: 21880378, PMCID: PMC3223326, DOI: 10.1016/j.tips.2011.07.006.Peer-Reviewed Original ResearchConceptsAldosterone systemΒ-cellsGlucose-stimulated insulin secretionIncidence of diabetesLarge clinical trialsInduces Insulin ResistanceCultured β-cellsPancreatic β-cellsRAAS inhibitionAng IIAngiotensin IIInsulin resistanceHeart diseaseClinical trialsDiabetes progressionMineralocorticoid receptorPharmacological strategiesInsulin secretionGlucose homeostasisPancreatic isletsOxidative stressDiabetesIndependent mechanismsGlucose transportCellular levelAldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets
Luther JM, Luo P, Kreger MT, Brissova M, Dai C, Whitfield TT, Kim HS, Wasserman DH, Powers AC, Brown NJ. Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets. Diabetologia 2011, 54: 2152-2163. PMID: 21519965, PMCID: PMC3216479, DOI: 10.1007/s00125-011-2158-9.Peer-Reviewed Original ResearchConceptsWild-type miceGlucose-stimulated insulin secretionHigh sodium intakeEffects of aldosteroneInsulin secretionSodium intakeHyperglycaemic clampInsulin sensitivityEuglycaemic–hyperinsulinaemic clamp studiesSuperoxide dismutase mimetic tempolRelative aldosterone excessMineralocorticoid receptor antagonismDismutase mimetic tempolMineralocorticoid receptor antagonistsC-peptide concentrationsOnset of diabetesConclusions/interpretationWeMIN6 beta-cell lineBeta-cell lineAldosterone excessRenin activityGlucose intoleranceAldosterone deficiencyAngiotensin IIReceptor antagonism
2009
Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome
Hill KD, Eckhauser AW, Marney A, Brown NJ. Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome. Diabetes Care 2009, 32: 857-859. PMID: 19196886, PMCID: PMC2671107, DOI: 10.2337/dc08-1862.Peer-Reviewed Original ResearchConceptsBeta-cell functionPhosphodiesterase-5 inhibitionMetabolic syndromeInsulin sensitivityPlasma renin activityDiastolic blood pressureΒ-cell functionRenin activityBlood pressureACE inhibitionAngiotensin IIFibrinolytic parametersACE activityGlucose homeostasisSeparate daysSyndromeRamiprilFibrinolysisTadalafilInhibitionTreatmentNovel strategyPlaceboResearch designWomen