Despite important empirical findings, current models of the oral glucose tolerance test (OGTT) do not incorporate the essential contributions of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, to glucose-stimulated insulin secretion. In order to address this deficiency, a model was, therefore, developed in which the incretins, as well as a term reflecting net hepatic glucose balance, were included. Equations modeling the changes in incretins, hepatic glucose balance, insulin and glucose were used to simulate the responses to 50 and 100 g oral glucose loads under normal conditions. The model successfully captures main trends in mean data from the literature using a simple 'lumped-parameter,' single-compartment approach in which the majority of the parameters were matched to known clinical data. The accuracy of the model and its applicability to understanding fundamental mechanisms was further assessed using a variety of glycemic and insulinemic challenges beyond those which the model was originally created to encompass, including hyper- and hypoinsulinemia, changes in insulin sensitivity, and the insulin infusion-modified intravenous glucose tolerance test.
We describe in detail a reliable experimental protocol for c-fos immuno-labeling of patterns of neural activation in the chinchilla (chinchilla laniger). We report on resting-level neural activity in inferior colliculus (IC) of auditory midbrain, and on tonotopic bands present following 90 min of pure-tone sound stimulation. Neurons activated by 6-kHz sound stimulation lay ventro-medial to those activated at 2 kHz. This is consistent with the known tonotopic organization of IC, and verified in the present report by multi-unit neuron response recordings in central nucleus of IC. Of particular interest, we observe a significant reduction in cell labeling adjacent to the tonotopic bands, and suggest that such decreases represent inhibitory regions. C-fos-labeled bands and lateral regions of reduced labeling resemble excitatory and lateral-inhibitory response areas of IC neurons.
It is well known that discrimination response variability increases with stimulus intensity, closely related to Weber's Law. It is also an axiom that sensation magnitude increases with stimulus intensity. Following earlier researchers such as Thurstone, Garner, and Durlach and Braida, we explored a new method of exploiting these relationships to estimate the power function exponent relating sound pressure level to loudness, using the accuracy with which listeners could identify the intensity of pure tones. The log standard deviation of the normally distributed identification errors increases linearly with stimulus range in decibels, and the slope, a, of the regression is proportional to the loudness exponent, n. Interestingly, in a demonstration experiment, the loudness exponent estimated in this way is greater for females than for males.
Auditory brain areas undergo reorganization resulting from abnormal sensory input during early postnatal development. This is evident from studies at the cortical level but it remains unclear whether there is reorganization in the auditory midbrain in a species similar to the human, that is, with early hearing onset. We have explored midbrain plasticity in the chinchilla, a precocious species that matches the human in terms of hearing development. Neonatal chinchillas were chronically exposed to a 2 kHz narrowband sound at 70 dB SPL for 4 weeks. Tonotopic maps in inferior colliculus (central nucleus) were defined based on single neuron characteristic frequency. We hypothesized an overrepresentation of the 2 kHz region of the maps. However, we observed a significant decrease in the proportion of neurons dedicated to the 2 kHz octave band and also away from the exposure frequency at 8 kHz. In addition, we report a significant increase in low frequency representation (<1 kHz), again a change to tonotopic mapping distant to the 2 kHz region. Thus in a precocious species, tonotopic maps in auditory midbrain are altered following abnormal stimulation during development. However, these changes are more complex than the overrepresentation of exposure related frequency regions that are often reported.
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