Genetic interaction between hyperglycemic QTLs is manifested under a high calorie diet in OLETF-derived congenic rats.

The condition of hyperglycemia results from multiple genetic and environmental factors. In recent years much progress has been made with regards to the search for candidate genes involved in the expression of various common diseases including type 2 diabetes. However less is known about the specific genetic and environmental connections that are important for the development of the disease. In the present study, we used hyperglycemic congenic rats to address this issue. When given a normal diet, two hyperglycemic QTLs (quantitative trait locus), Nidd2/of and Nidd10/of, showed mild obesity and/or increased blood glucose in the oral glucose tolerance test. In a double congenic strain possessing both loci, these indices were not significantly different from those of either single congenic strain. In contrast, the double congenic strain fed a high-calorie diet showed significantly greater body weight than the single congenic strains or normoglycemic control rats. Although postprandial glucose levels of the double congenic rat were not further aggravated even on the high fat diet, it was notable that the postprandial insulin levels were drastically elevated. From these results, we constructed a novel model animal especially for the study of prediabetic hyperinsulemia, in which two QTLs and an additional dietary condition are involved. This may help to shed light on the genetic basis and gene-to-diet interaction during the early stage of type 2 diabetes.

Volitional hyperventilation during ramp exercise to exhaustion.

The purpose of this study was to determine whether volitional hyperventilation at 20 L x min(-1) above normal exercise values affected exercise duration while performing ramp exercise to exhaustion. Nine healthy subjects performed a ramp exercise test to exhaustion. On a subsequent test they hyperventilated, with the aid of visual and audio feedback, at 20 L x min(-1) greater than their initial test. Ramp exercise time to exhaustion was substantially reduced from 771.6 +/- 85.2 s to 726.6 +/- 86.6 s (p < 0.002) with the additional hyperventilation. Subjects underwent 2 more ramp exercise tests and performed a 5 s maximum voluntary ventilation or a forced vital capacity test at work rates corresponding to rest, below lactate threshold (LT), above LT, immediately after exercise, and 3 min recovery. Generally, the flow rates were not affected by exercise below LT and were enhanced during above-LT exercise, exhaustion, and recovery. This indicated a change in pulmonary function that is dependent on exercise intensity. In spite of this increased ability to generate high flow rates, exercise performance was diminished when respiratory muscle work was increased volitionally by 20 L x min(-1), indicating a strong coupling between respiratory muscle work and fatigue during ramp exercise in normal subjects.