ABSTRACT
Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated sodium and calcium channels for GLP-1 secretion. Primary murine L-cells were identified and purified using transgenic mice expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. GLP-1 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin reduced both basal and glutamine-stimulated GLP-1 secretion. Voltage gated calcium channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that GLP-1 release was blocked both by nifedipine and ω-conotoxin MVIIC. We observed large voltage-dependent potassium currents, but only a small chromanol sensitive current that might be attributable to KCNQ1. GLP-1 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type calcium currents. The concept of an electrically excitable L-cell provides a basis for understanding how GLP-1 release may be modulated by nutrient, hormonal and pharmaceutical stimuli.
Subject(s)
Electric Stimulation , Enteroendocrine Cells/metabolism , Glucagon-Like Peptide 1/metabolism , Action Potentials/physiology , Animals , Calcium/metabolism , Calcium Channel Blockers/pharmacology , Calcium Channels/genetics , Calcium Channels/metabolism , Cells, Cultured , Electrophysiology , Enteroendocrine Cells/drug effects , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Ion Channel Gating/drug effects , Ion Channel Gating/physiology , Mice , Mice, Transgenic , Nifedipine/pharmacology , Oligonucleotide Array Sequence Analysis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
The sound attenuation characteristics of two military helmets were measured using an acoustic manikin as the test apparatus. The manikin results are compared to the results of attenuation measurements made on human subjects wearing identical helmets. The testing room and instrumentation were the same for both the manikin and human subjects. Procedures in ANSI S3.19-1974 were used in the real-ear attentuation at threshold (REAT) part of this study. The results are encouraging as they suggest that the manikin may be used in place of a panel of human subjects to evaluate the hearing protection characteristics of military head gear.
Subject(s)
Acoustics , Ear Protective Devices , Head Protective Devices , Protective Devices , Adult , Auditory Threshold , Hair , Hearing Tests , Humans , Male , ManikinsABSTRACT
Five measures of the items of the Multiple-Choice Intelligibility Test were obtained: apparent aural similarity of the four words available to a listener on hearing a stimulus, interconsonantal differences among the prevocalic portions of these words, phonemic discrepancies among these words, distinctive feature differences among these words, and the pooled discrimination score of the four words that were available to the responder on hearing the stimulus. The last score was made the target in a multiple correlation problem, and the relative contribution, combined and separately, of the four remaining measures to the target measure was determined. These four measures accounted for approximately 45% of the variance among the scores of discrimination. The strongest contributors were apparent aural similarity of the available responses and the phonemic discrepancy among the available responses.
Subject(s)
Discrimination Learning , Speech Perception , Cues , Humans , Phonetics , Psycholinguistics , Speech IntelligibilityABSTRACT
The present study was designed to survey the noise characteristics in residence halls housing young mentally retarded children and test the effects of this noise on speech-discrimination performance of the residents. The noise survey indicated that the mean level of the noise was 75 dB SPL (WIth the level greater than 70 dB SPL during 71 percent of the sampling time). The spectrum was similar in configuration to the long-time speech spectrum. Selected residents were tested for speech discrimination in quiet and noise conditions. Mean scores on the Word Intelligibility by Perception Identification test were 73.9 percent correct in the quiet and 44 percent correct in the noise conditions. We concluded that the residents, who already had a primary language-learning handicap, were being subjected to a possible secondary impediment resulting from their living environment.
