Postprandial Hypotension due to a Lack of Sympathetic Compensation in Patients with Diabetes Mellitus.

Postprandial hypotension is an important hemodynamic abnormality in diabetes mellitus, but few reports are available on the relationship between autonomic dysfunction and postprandial hypotension. Ten diabetic patients and 10 healthy volunteers were recruited for this study. Postural blood pressure and heart rate changes were measured before lunch, and then the hemodynamic responses to a standardized meal were investigated. Holter electrocardiogram (ECG) monitoring was conducted for assessing spectral powers and time-domain parameters of RR variations. Postural changes from the supine to the upright position decreased the systolic blood pressure of the diabetics from 133(+-)16 to 107(+-)20 mmHg (p<0.01), but did not decrease the systolic blood pressure of the controls. The heart rate remained constant in the diabetics but was increased in the controls. Food ingestion decreased systolic blood pressure in the diabetics, with a maximum reduction of 25(+-)5 mmHg. This decrease was not associated with any changes in the ratio of low frequency to high frequency, and yet the heart rate remained almost constant. Indexes involving parasympathetic tone were not affected. Food ingestion did not affect blood pressure in the control group. These findings suggest that lack of compensatory sympathetic activation is a factor contributing to postprandial hypotension in diabetics, and that parasympathetic drive does not make a significant contribution to this condition

A role for BiP as an adjustor for the endoplasmic reticulum stress-sensing protein Ire1

In the unfolded protein response, the type I transmembrane protein Ire1 transmits an endoplasmic reticulum (ER) stress signal to the cytoplasm. We previously reported that under nonstressed conditions, the ER chaperone BiP binds and represses Ire1. It is still unclear how this event contributes to the overall regulation of Ire1. The present Ire1 mutation study shows that the luminal domain possesses two subregions that seem indispensable for activity. The BiP-binding site was assigned not to these subregions, but to a region neighboring the transmembrane domain. Phenotypic comparison of several Ire1 mutants carrying deletions in the indispensable subregions suggests these subregions are responsible for multiple events that are prerequisites for activation of the overall Ire1 proteins. Unexpectedly, deletion of the BiP-binding site rendered Ire1 unaltered in ER stress inducibility, but hypersensitive to ethanol and high temperature. We conclude that in the ER stress-sensory system BiP is not the principal determinant of Ire1 activity, but an adjustor for sensitivity to various stresses